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1.
Eur Radiol ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662099

RESUMO

OBJECTIVES: Basilar artery occlusion (BAO) may be etiologically attributed to embolism or in situ thrombosis due to basilar stenosis (BS). Patients with BAO due to BS (BAOS) are known to have worse outcomes than patients with embolic occlusions (BAOE). BAOS occurs more proximally in the basilar artery (BA) than BAOE. We hypothesize that differing brain stem infarct patterns contribute to outcome differences between these stroke etiologies. METHODS: This retrospective study includes 199 consecutive patients with BAO who received endovascular treatment at a single center. Final infarction in brain parenchyma dependent on the posterior circulation was graded semiquantitatively on magnetic resonance imaging (MRI). Associations to underlying stenosis and angiographic and clinical outcome variables were tested. The primary endpoint was early good clinical outcome (EGCO, mRS score ≤ 3 at discharge). RESULTS: Infarct extension of the medulla oblongata (OR = 0.25; 95% CI = 0.07-0.86; p = 0.03), the inferior pons (OR = 0.328; 95% CI = 0.17-0.63; p = 0.001), the superior pons (OR = 0.57; 95% CI = 0.33-0.99; p = 0.046), and the occipital lobes (OR = 0.46; 95% CI = 0.26-0.80; p = 0.006) negatively predicted EGCO. Infarct extension for other posterior-circulation-dependent brain regions was not independently associated with unfavorable early outcomes. Patients with BAOS had more proximal occlusions and greater infarct volumes in the inferior brain stem. Successful reperfusion (mTICI 2b-3) occurred more often in patients with BAOE than in BAOS (BAOE: 131 (96.3%); BAOS: 47 (83.9%), p = 0.005). CONCLUSION: Unfavorable early outcomes in patients with BAOS may be explained by a higher likelihood of inferior brain stem infarcts and lower rates of reperfusion success. CLINICAL RELEVANCE STATEMENT: Basilar artery occlusion due to underlying stenosis is associated with a poorer prognosis than that caused by embolism; these results suggest that aggressive endovascular therapy, usually involving the placement of a permanent stent, may be warranted in these patients. KEY POINTS: Inferior brain stem and occipital infarcts are prognostically unfavorable in basilar artery occlusion. Basilar artery occlusion due to stenosis occurs more proximally and is associated with worse outcomes. Differentiating etiologies of basilar artery occlusion may influence how aggressively treated the occlusion is.

2.
Stroke ; 54(5): 1246-1256, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37051911

RESUMO

BACKGROUND: Bone or cartilage anomalies with affection of brain supplying arteries are a potential structural cause for ischemic stroke. In the following, we termed this entity bony stroke. Due to rarity of their description, there is no standardized workup and therapy for bony strokes. METHODS: Retrospectively, we extracted diagnostic and therapeutic workup of all patients considered to have had a bony stroke between January 2017 to March 2022 at our comprehensive care center. RESULTS: In total, 6 patients classified as a bony stroke were identified among 4200 acute patients with ischemic stroke treated during the study period. Each patient had recurrent ischemic strokes in the dependent vascular territory before diagnosis. Diagnosis was achieved by a combination of imaging devices, including sonography, computed tomography, and magnetic resonance imaging. In addition to conventional static imaging, the application of dynamic imaging modalities with the patients' head in rotation or reclination confirmed a vessel affection following head movements in 3 patients (50%). Treatment options were interdisciplinary assessed and included the following: conservative treatment (n=1), endovascular stenting (n=2) or occlusion (n=2), surgical removal of bone/ cartilage (n=2), and surgical bypass treatment (n=1). In follow-up (mean 11.7 months), no patient experienced further ischemia. CONCLUSIONS: As a differential diagnosis, bony strokes may be considered in patients with recurrent ischemic stroke of unknown cause in one dependent vascular territory. Interdisciplinary evaluation and treatment may eliminate risk of stroke recurrence.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/complicações , Estresse Mecânico , Estudos Retrospectivos , Artérias , Encéfalo , Isquemia Encefálica/terapia
3.
Alzheimers Dement ; 19(4): 1152-1163, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35876563

RESUMO

INTRODUCTION: It remains unknown whether the global small vessel disease (SVD) burden predicts post-stroke outcomes. METHODS: In a prospective multicenter study of 666 ischemic and hemorrhagic stroke patients, we quantified magnetic resonance imaging (MRI)-based SVD markers (lacunes, white matter hyperintensities, microbleeds, perivascular spaces) and explored associations with 6- and 12-month cognitive (battery of 15 neuropsychological tests) and functional (modified Rankin scale) outcomes. RESULTS: A global SVD score (range 0-4) was associated with cognitive impairment; worse performance in executive function, attention, language, and visuospatial ability; and worse functional outcome across a 12-month follow-up. Although the global SVD score did not improve prediction, individual SVD markers, assessed across their severity range, improved the calibration, discrimination, and reclassification of predictive models including demographic, clinical, and other imaging factors. DISCUSSION: SVD presence and severity are associated with worse cognitive and functional outcomes 12 months after stroke. Assessing SVD severity may aid prognostication for stroke patients. HIGHLIGHTS: In a multi-center cohort, we explored associations of small vessel disease (SVD) burden with stroke outcomes. SVD burden associates with post-stroke cognitive and functional outcomes. A currently used score of SVD burden does not improve the prediction of poor outcomes. Assessing the severity of SVD lesions adds predictive value beyond known predictors. To add predictive value in assessing SVD in stroke patients, SVD burden scores should integrate lesion severity.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Acidente Vascular Cerebral , Humanos , Estudos Prospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Doenças de Pequenos Vasos Cerebrais/patologia , Disfunção Cognitiva/complicações , Imageamento por Ressonância Magnética , Cognição
4.
J Clin Ultrasound ; 50(4): 487-490, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34537972

RESUMO

Rising numbers of mechanical thrombectomies in treatment of acute stroke emphasize the need for appropriate follow-up to identify potential complications in time. Recent findings suggest that abnormal hemodynamics post-recanalization are associated with worse outcomes. Here, we present the case of a patient who exhibited an increased blood flow velocity on transcranial color-coded duplex sonography (TCCD) following endovascular intervention shortly before suffering a reocclusion of the recanalized vessel. Our example shows that TCCD may serve as a valuable tool for detecting patients at risk for secondary vascular events after mechanical thrombectomy.


Assuntos
Acidente Vascular Cerebral , Trombectomia , Velocidade do Fluxo Sanguíneo/fisiologia , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Trombectomia/efeitos adversos , Resultado do Tratamento
5.
Int J Mol Sci ; 23(16)2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-36012739

RESUMO

Although a pathophysiological impact remains difficult to prove in individual patient care, a patent foramen ovale (PFO) is currently considered of high relevance for secondary prophylaxis in selected patients with cryptogenic ischemic stroke. By quantification of histological clot composition, we aimed to enhance pathophysiological understanding of PFO attributable ischemic strokes. Retrospectively, we evaluated all cerebral clots retrieved by mechanical thrombectomy for acute ischemic stroke treatment between 2011 and 2021 at our comprehensive stroke care center. Inclusion criteria applied were cryptogenic stroke, age (≤60 years), and PFO status according to transesophageal echocardiography, resulting in a study population of 58 patients. Relative clot composition was calculated using orbit image analysis to define the ratio of main histologic components (fibrin/platelets (F/P), red blood cell count (RBC), leukocytes). Cryptogenic stroke patients with PFO (PFO+, n = 20) displayed a significantly higher percentage of RBC (0.57 ± 0.17; p = 0.002) and lower percentage of F/P (0.38 ± 0.15; p = 0.003) compared to patients without PFO (PFO-, n = 38) (RBC: 0.41 ± 0.21; F/P: 0.52 ± 0.20). In conclusion, histologic clot composition in cryptogenic stroke varies depending on the presence of a PFO. Our findings histologically support the concept that a PFO may be of pathophysiological relevance in cryptogenic ischemic stroke.


Assuntos
Forame Oval Patente , AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Ecocardiografia Transesofagiana/métodos , Forame Oval Patente/complicações , Forame Oval Patente/diagnóstico por imagem , Humanos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/etiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/etiologia , Trombose/complicações
6.
Nervenarzt ; 93(4): 377-384, 2022 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-34932125

RESUMO

Long-term management after stroke has not been standardized in contrast to acute and rehabilitative stroke care. The fragmented outpatient sector of healthcare allows a high degree of flexibility but also variability in the quality of care provided. The commission on long-term stroke care of the German Stroke Society developed a concept on how to provide standardized multiprofessional long-term stroke care with a focus on patient-centered comprehensive care. We propose a diagnostic work-up in stages, with an initial patient-reported screening, followed by an adapted in-depth assessment of affected domains. This includes internistic domains (management of risk factors) and also genuine neurological domains (spasticity, cognitive deficits etc.) that must be considered. This information is then merged with patient expectations and prioritization to a standardized treatment plan. Special challenges for the implementation of such a comprehensive care system are the intersectoral and intrasectoral communication between healthcare providers, patients and relatives, the need to create a compensation system for providers and the establishment of appropriate quality management services. Digital health applications are helpful tools to provide aspects of diagnostics, treatment and communication in long-term stroke care.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Assistência ao Convalescente , Humanos , Assistência de Longa Duração , Pacientes Ambulatoriais , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia
7.
BMC Med Imaging ; 21(1): 91, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034677

RESUMO

BACKGROUND: To compare the quality of free-text reports (FTR) and structured reports (SR) of brain magnetic resonance imaging (MRI) examinations in patients following mechanical thrombectomy for acute stroke treatment. METHODS: A template for SR of brain MRI examinations based on decision trees was designed and developed in house and applied to twenty patients with acute ischemic stroke in addition to FTR. Two experienced stroke neurologists independently evaluated the quality of FTR and SR regarding clarity, content, presence of key features, information extraction, and overall report quality. The statistical analysis for the differences between FTR and SR was performed using the Mann-Whitney U-test or the Chi-squared test. RESULTS: Clarity (p < 0.001), comprehensibility (p < 0.001), inclusion of relevant findings (p = 0.016), structure (p = 0.005), and satisfaction with the content of the report for immediate patient management (p < 0.001) were evaluated significantly superior for the SR by both neurologist raters. One rater additionally found the explanation of the patient's clinical symptoms (p = 0.003), completeness (p < 0.009) and length (p < 0.001) of SR to be significantly superior compared to FTR and stated that there remained no open questions, requiring further consultation of the radiologist (p < 0.001). Both neurologists preferred SR over FTR. CONCLUSIONS: The use of SR for brain magnetic resonance imaging may increase the report quality and satisfaction of the referring physicians in acute ischemic stroke patients following mechanical thrombectomy. Trial registration Retrospectively registered.


Assuntos
AVC Isquêmico/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Trombólise Mecânica , Prontuários Médicos/normas , Doença Aguda , Idoso , Encéfalo/diagnóstico por imagem , Compreensão , Humanos , AVC Isquêmico/cirurgia
8.
J Clin Ultrasound ; 48(8): 498-502, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31957886

RESUMO

We present an 81-year old male in whom a routine carotid artery ultrasonographic follow-up examination incidentally revealed a large, free-floating thrombus (FFT) of the right internal carotid artery. This case focuses on the clinical decision-making regarding FFTs, which constitute a rare condition lacking a diagnostic gold standard with few available data concerning optimum treatment and natural course-in particular regarding patients in whom FFT is an incidental finding. We were able to demonstrate the accuracy of carotid artery ultrasonography in the detection as well as follow-up of FFT. Of clinical interest is furtherly a possible partial disappearance by spontaneous re-adhesion or resolution of the FFT.


Assuntos
Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Trombose/diagnóstico por imagem , Idoso de 80 Anos ou mais , Artéria Carótida Primitiva/patologia , Artéria Carótida Interna/patologia , Tomada de Decisão Clínica , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Trombose/patologia
9.
J Stroke Cerebrovasc Dis ; 29(11): 105175, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066900

RESUMO

BACKGROUND: The COVID-19 pandemic caused public lockdowns around the world. We analyzed if the public lockdown altered the referral pattern of Code Stroke patients by Emergency Medical Services (EMS) to our Comprehensive Stroke Center. METHODS: Retrospective single-center study at a Bavarian Comprehensive Stroke Center. Patients who were directly referred to our stroke unit by EMS between the 1st of January 2020 and the 19th of April 2020 were identified and number of referrals, clinical characteristics and treatment strategies were analyzed during the public lockdown and before. The public lockdown started on 21st of March and ended on 19th April 2020. RESULTS: In total 241 patients were referred to our center during the study period, i.e. 171 before and 70 during the lockdown. The absolute daily number of Code Stroke referrals and the portion of patients with stroke mimics remained stable. The portion of female stroke patients decreased (55% to 33%; p = 0.03), and stroke severity as measured by the National Institutes of Health Stroke Scale (median 3 (IQR 0-7) versus 6 (IQR 1-15.5) points; p = 0.04) increased during the lockdown. There was no difference of daily numbers of patients receiving thrombolysis and thrombectomy. CONCLUSIONS: Referral of Code Stroke patients by EMS could be maintained sufficiently despite the COVID-19 pandemic lockdown. However, patients' health care utilization of the EMS may have changed within the public lockdown. EMS remains a useful tool for Code Stroke patient referral during lockdowns, but public education about stroke is required prior to further lockdowns.


Assuntos
Infecções por Coronavirus/terapia , Prestação Integrada de Cuidados de Saúde/tendências , Serviços Médicos de Emergência/tendências , Pneumonia Viral/terapia , Distância Psicológica , Quarentena , Encaminhamento e Consulta/tendências , Acidente Vascular Cerebral/terapia , Trombectomia/tendências , Terapia Trombolítica/tendências , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Aceitação pelo Paciente de Cuidados de Saúde , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo
12.
Circulation ; 132(13): 1261-9, 2015 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-26232277

RESUMO

BACKGROUND: We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). METHODS AND RESULTS: This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICHany), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICHECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICHNINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8-22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1-1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. CONCLUSIONS: IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.


Assuntos
Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Hemorragia Cerebral/induzido quimicamente , Inibidores do Fator Xa/uso terapêutico , Fibrinolíticos/uso terapêutico , Terapia Trombolítica , Doença Aguda , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/classificação , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Fibrilação Atrial/complicações , Isquemia Encefálica/sangue , Hemorragia Cerebral/epidemiologia , Estudos de Coortes , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento , Vitamina K/antagonistas & inibidores
13.
Cerebrovasc Dis ; 42(5-6): 415-420, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27438461

RESUMO

BACKGROUND: The first specific antidote for non-vitamin K antagonist oral anticoagulants (NOAC) has recently been approved. NOAC antidotes will allow specific treatment for 2 hitherto problematic patient groups: patients with oral anticoagulant therapy (OAT)-associated intracerebral hemorrhage (ICH) and maybe also thrombolysis candidates presenting on oral anticoagulation (OAT). We aimed to estimate the frequency of these events and hence the quantitative demand of antidote doses on a stroke unit. METHODS: We extracted data of patients with acute ischemic stroke and ICH (<24 h after symptom onset) in the years 2012-2015 from a state-wide prospective stroke inpatient registry. We selected 8 stroke units and determined the mode of OAT upon admission in 2012-2013. In 2015, the mode of OAT became a mandatory item of the inpatient registry. From the number of anticoagulated patients and the NOAC share, we estimated the current and future demand for NOAC antidote doses on stroke units. RESULTS: Eighteen percent of ICH patients within 6 h of symptom onset or an unknown symptom onset were on OAT. Given a NOAC share at admission of 40%, about 7% of all ICH patients may qualify for NOAC reversal therapy. Thirteen percent of ischemic stroke patients admitted within 4 h presented on anticoagulation. Given the availability of an appropriate antidote, a NOAC share of 50% could lead to a 6.1% increase in thrombolysis rate. CONCLUSIONS: Stroke units serving populations with a comparable demographic structure should prepare to treat up to 1% of all acute ischemic stroke patients and 7% of all acute ICH patients with NOAC antidotes. These numbers may increase with the mounting prevalence of atrial fibrillation and an increasing use of NOAC.


Assuntos
Anticoagulantes/efeitos adversos , Antídotos/provisão & distribuição , Hemorragia Cerebral/tratamento farmacológico , Necessidades e Demandas de Serviços de Saúde , Unidades Hospitalares , Avaliação das Necessidades , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/diagnóstico , Feminino , Previsões , Alemanha , Necessidades e Demandas de Serviços de Saúde/tendências , Unidades Hospitalares/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades/tendências , Sistema de Registros , Acidente Vascular Cerebral/diagnóstico , Terapia Trombolítica/efeitos adversos
14.
Proc Natl Acad Sci U S A ; 110(20): 8242-7, 2013 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-23630268

RESUMO

Synaptopodin (SP) is a marker and essential component of the spine apparatus (SA), an enigmatic cellular organelle composed of stacked smooth endoplasmic reticulum that has been linked to synaptic plasticity. However, SP/SA-mediated synaptic plasticity remains incompletely understood. To study the role of SP/SA in homeostatic synaptic plasticity we here used denervation-induced synaptic scaling of mouse dentate granule cells as a model system. This form of plasticity is of considerable interest in the context of neurological diseases that are associated with the loss of neurons and subsequent denervation of connected brain regions. In entorhino-hippocampal slice cultures prepared from SP-deficient mice, which lack the SA, a compensatory increase in excitatory synaptic strength was not observed following partial deafferentation. In line with this finding, prolonged blockade of sodium channels with tetrodotoxin induced homeostatic synaptic scaling in wild-type, but not SP-deficient, slice cultures. By crossing SP-deficient mice with a newly generated transgenic mouse strain that expresses GFP-tagged SP under the control of the Thy1.2 promoter, the ability of dentate granule cells to form the SA and to homeostatically strengthen excitatory synapses was rescued. Interestingly, homeostatic synaptic strengthening was accompanied by a compensatory increase in SP cluster size/stability and SA stack number, suggesting that activity-dependent SP/SA remodeling could be part of a negative feedback mechanism that aims at adjusting the strength of excitatory synapses to persisting changes in network activity. Thus, our results disclose an important role for SP/SA in homeostatic synaptic plasticity.


Assuntos
Denervação , Giro Denteado/citologia , Proteínas dos Microfilamentos/metabolismo , Plasticidade Neuronal , Animais , Canais de Cálcio/metabolismo , Espinhas Dendríticas/metabolismo , Córtex Entorrinal/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Hipocampo/metabolismo , Homeostase , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Técnicas de Patch-Clamp , Regiões Promotoras Genéticas , Receptores de N-Metil-D-Aspartato/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Sinapses/metabolismo , Tetrodotoxina/farmacologia
15.
Hippocampus ; 24(8): 1030-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24753100

RESUMO

Thrombin and other clotting factors regulate long-term potentiation (LTP) in the hippocampus through the activation of the protease activated receptor 1 (PAR1) and consequent potentiation of N-methyl-d-aspartate receptor (NMDAR) functions. We have recently shown that the activation of PAR1 either by thrombin or the anticoagulant factor activated protein C (aPC) has differential effects on LTP. While thrombin activation of PAR1 induces an NMDAR-mediated slow onset LTP, which saturates the ability to induce further LTP in the exposed network, aPC stimulation of PAR1 enhances tetanus induced LTP through a voltage-gated calcium channels mediated mechanism. In this study, we addressed the mechanisms by which aPC enhances LTP in hippocampal slices. Using extracellular recordings, we show that a short tetanic stimulation, which does not induce LTP, is able to enhance plasticity in the presence of aPC through a mechanism that requires the activation of sphingosine-1 phosphate receptor 1 and intracellular Ca(2+) stores. These data identify aPC as a "metaplastic molecule", capable of shifting the threshold of LTP towards further potentiation. Our findings propose novel strategies to enhance plasticity in neurological diseases associated with the breakdown of the blood brain barrier and alterations in synaptic plasticity.


Assuntos
Hipocampo/fisiologia , Potenciação de Longa Duração/fisiologia , Neurônios/fisiologia , Proteína C/metabolismo , Receptor PAR-1/metabolismo , Receptores de Lisoesfingolipídeo/metabolismo , Animais , Fatores de Coagulação Sanguínea/metabolismo , Cálcio/metabolismo , Estimulação Elétrica , Hipocampo/efeitos dos fármacos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Receptores de Superfície Celular/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de Esfingosina-1-Fosfato , Técnicas de Cultura de Tecidos
16.
Eur Radiol Exp ; 8(1): 52, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38575701

RESUMO

BACKGROUND: Nowadays, there is no method to quantitatively characterize the material composition of acute ischemic stroke thrombi prior to intervention, but dual-energy CT (DE-CT) offers imaging-based multimaterial decomposition. We retrospectively investigated the material composition of thrombi ex vivo using DE-CT with histological analysis as a reference. METHODS: Clots of 70 patients with acute ischemic stroke were extracted by mechanical thrombectomy and scanned ex vivo in formalin-filled tubes with DE-CT. Multimaterial decomposition in the three components, i.e., red blood cells (RBC), white blood cells (WBC), and fibrin/platelets (F/P), was performed and compared to histology (hematoxylin/eosin staining) as reference. Attenuation and effective Z values were assessed, and histological composition was compared to stroke etiology according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. RESULTS: Histological and imaging analysis showed the following correlation coefficients for RBC (r = 0.527, p < 0.001), WBC (r = 0.305, p = 0.020), and F/P (r = 0.525, p < 0.001). RBC-rich thrombi presented higher clot attenuation in Hounsfield units than F/P-rich thrombi (51 HU versus 42 HU, p < 0.01). In histological analysis, cardioembolic clots showed less RBC (40% versus 56%, p = 0.053) and more F/P (53% versus 36%, p = 0.024), similar to cryptogenic clots containing less RBC (34% versus 56%, p = 0.006) and more F/P (58% versus 36%, p = 0.003) than non-cardioembolic strokes. No difference was assessed for the mean WBC portions in all TOAST groups. CONCLUSIONS: DE-CT has the potential to quantitatively characterize the material composition of ischemic stroke thrombi. RELEVANCE STATEMENT: Using DE-CT, the composition of ischemic stroke thrombi can be determined. Knowledge of histological composition prior to intervention offers the opportunity to define personalized treatment strategies for each patient to accomplish faster recanalization and better clinical outcomes. KEY POINTS: • Acute ischemic stroke clots present different recanalization success according to histological composition. • Currently, no method can determine clot composition prior to intervention. • DE-CT allows quantitative material decomposition of thrombi ex vivo in red blood cells, white blood cells, and fibrin/platelets. • Histological clot composition differs between stroke etiology. • Insights into the histological composition in situ offer personalized treatment strategies.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Humanos , Fibrina/análise , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/terapia , Trombose/diagnóstico por imagem , Trombose/patologia , Trombose/terapia , Tomografia Computadorizada por Raios X/métodos
17.
J Neurointerv Surg ; 15(11): 1129-1135, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36539271

RESUMO

BACKGROUND: Post-stroke diffusion weighted imaging (DWI) signal transformation of the infarct core, which results in high apparent diffusion coefficient (ADC) values and variable DWI signal intensity, is completed no later than 1 month after onset of ischemia. We observed frequent exceptions to this timeline of change in DWI signal, which led to uncertainties in further clinical patient management. METHODS: A prospective single-center study of patients treated with mechanical thrombectomy of a large vessel occlusion in the anterior circulation was conducted. Patients received high-resolution MRI at 3T, including DWI, in the acute post-stroke phase and in the follow-up after 3-12 months. RESULTS: Overall, 78 patients (45 men) of mean age 63.6 years were evaluated. We identified persisting or new diffusion restriction in 29 of the 78 patients (37.2%) on follow-up imaging. Diffusion restrictions in a different location from the infarct core, representing new (sub-)acute ischemia, were observed in four patients (5.1%). Smaller areas of persisting diffusion restriction (pDWI lesions with high DWI signal and reduced ADC values) within the former infarct core were observed in 25 patients (32.1%) without clinical evidence of recurrent stroke, but with worse outcome scores at follow-up compared with patients without pDWI lesions. The presence of pDWI lesions is associated with a large primary infarct core (multivariate regression OR 1.03 (95% CI 1.01 to 1.05); p<0.01), mediating the relationship between pDWI lesions and clinical outcome. CONCLUSION: Smaller foci of persisting diffusion restriction (pDWI lesions) in the follow-up after endovascular treatment for stroke are frequent and likely represent a slowed ADC signal progression within a formerly large infarct core.

18.
J Neurol ; 270(3): 1501-1511, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36411388

RESUMO

BACKGROUND: Genetic variants are considered to have a crucial impact on the occurrence of ischemic stroke. In clinical routine, the diagnostic value of next-generation sequencing (NGS) in the medical clarification of acute juvenile stroke has not been investigated so far. MATERIAL AND METHODS: We analyzed an exome-based gene panel of 349 genes in 172 clinically well-characterized patients with magnetic resonance imaging (MRI)-proven, juvenile (age ≤ 55 years), ischemic stroke admitted to a single comprehensive stroke center. RESULTS: Monogenetic diseases causing ischemic stroke were observed in five patients (2.9%): In three patients with lacunar stroke (1.7%), we identified pathogenic variants in NOTCH3 causing cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Hence, CADASIL was identified at a frequency of 12.5% in the lacunar stroke subgroup. Further, in two male patients (1.2%) suffering from lacunar and cardioembolic stroke, pathogenic variants in GLA causing Fabry's disease were present. Additionally, genetic variants in monogenetic diseases lacking impact on stroke occurrence, variants of unclear significance (VUS) in monogenetic diseases, and (cardiovascular-) risk genes in ischemic stroke were observed in a total of 15 patients (15.7%). CONCLUSION: Genetic screening for Fabry's disease in cardioembolic and lacunar stroke as well as CADASIL in lacunar stroke might be beneficial in routine medical work-up of acute juvenile ischemic stroke.


Assuntos
CADASIL , Doença de Fabry , AVC Isquêmico , Acidente Vascular Cerebral Lacunar , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , CADASIL/diagnóstico por imagem , CADASIL/genética , Acidente Vascular Cerebral Lacunar/genética , AVC Isquêmico/genética , Doença de Fabry/genética , Exoma , Receptor Notch3/genética , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/genética , Receptores Notch/genética , Imageamento por Ressonância Magnética , Mutação/genética
19.
Heliyon ; 9(3): e14508, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36942245

RESUMO

Objectives: Endovascular treatment of acute stroke patients with large vessel occlusions is well established. But tandem lesions of the internal carotid artery and the intracranial anterior circulation remain a challenge regarding the technical conditions and the putative higher risk of hemorrhage due to often required antiplatelet therapy.This study aims to evaluate the clinical outcome and the risk of hemorrhage after endovascular treatment of tandem lesions, with special regard to the periprocedural antiplatelet regimen. Materials and Methods: In this retrospective study, we included 63 consecutive stroke patients with endovascular treated tandem lesions. One hundred eleven patients with a solitary intracranial occlusion were matched using a "propensity score-matched analysis" with the covariates sex, age, wake-up stroke, iv-thrombolysis and NIHSS. Results: Rates of successful recanalization (mTICI 2b/3) and periprocedural complications were equal in both groups (P = 0.19; P = 0.35). The rate of good clinical outcome (mRS≤2) was similar, and the incidence of symptomatic hemorrhages was not significantly different (7.9% tandem lesions vs. 5.4% isolated intracranial occlusion, P = 0.51). Even intensified antiplatelet therapy in patients with tandem lesions did not increase the rate of symptomatic intracranial hemorrhages (P = 0.87). Conclusions: Clinical outcome and symptomatic intracranial hemorrhages did not differ significantly between endovascular treated patients with tandem lesions and matched patients with solitary intracranial occlusions, regardless of the antiplatelet regimen. Therefore, the complex technical requirements for recanalization of a tandem lesion and the putative higher risk should not result in reluctant treatment that would decrease the chance of a good clinical outcome.

20.
Sci Rep ; 13(1): 5730, 2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-37029202

RESUMO

Mechanical thrombectomy (MT) is frequently performed for distal medium vessel occlusions (DMVO) of the anterior circulation in acute stroke patients. However, evidence for its clinical benefit remains scarce. In this study, we aim to investigate clinical course and safety outcomes of MT in comparison to standard medical therapy (SMT) in DMVO. This single-center retrospective observational study included 138 consecutive patients treated for DMVO of the anterior circulation between 2015 and 2021. To reduce the risk of selection bias, propensity score matching (PSM) of patients with MT versus SMT was performed for the covariates NIHSS and mRS at admission. Out of all 138 patients, 48 (34.8%) received MT and 90 (65.2%) received SMT only. Overall, patients treated with MT showed significantly higher NIHSS and mRS scores at admission. Post 1:1 PSM, there was a trend toward a better NIHSS improvement in patients with MT (median 4 vs. 1, P = 0.1). No significant differences were observed in the occurrence of symptomatic intracranial hemorrhage or mortality between the groups before and after PSM. A subgroup analysis showed significantly higher NIHSS improvement (median 5 versus 1, P = 0.01) for patients with successful MT (≥ mTICI 2b). Mechanical thrombectomy for distal medium vessel occlusions (DMVO) in the anterior circulation appeared safe and feasible. Successful recanalization was associated with clinical improvement. Larger, multi-center, randomized-controlled trials are required to corroborate these findings.


Assuntos
Isquemia Encefálica , Transtornos Cerebrovasculares , Acidente Vascular Cerebral , Humanos , Trombectomia/efeitos adversos , Transtornos Cerebrovasculares/etiologia , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/etiologia , Hemorragias Intracranianas/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Isquemia Encefálica/etiologia
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