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INTRODUCTION: Intracranial artery calcification (ICAC) is a common finding on computed tomography (CT) in patients presenting with large vessel occlusion acute ischemic stroke (LVO-AIS) and could serve as a useful biomarker of intracranial atherosclerosis and altered intracranial vessel pliability in patients undergoing endovascular thrombectomy (EVT). METHODS: This was a retrospective cohort study analyzing consecutive patients undergoing CT head prior to EVT between 2016 and 2020. Extent of ICAC proximal to the target vessel was scored using a validated grading scale examining thickness and circumferential extent of calcifications. The relationship between 3 levels of ICAC burden and procedural, clinical, and safety outcomes was analyzed. RESULTS: Among 86 patients meeting inclusion criteria, ICAC of any degree was present in 72.1%. Median ICAC score was 3 [IQR 0-4]. There was a U-shaped association between ICAC score and successful reperfusion: 90.9%, 65.7%, and 94.4% in the low, intermediate, and high ICAC score groups, respectively (pâ¯=â¯0.008). Use of rescue intervention, most often angioplasty and stenting, was greatest in the high ICAC score group: 3.0% vs. 5.7% vs. 22.2% (pâ¯=â¯0.05). Functional independence at 90 days did not differ significantly among groups (41.7% vs. 31.0% vs. 15.4%, pâ¯=â¯0.26), nor did rates of symptomatic intracranial hemorrhage (15.2% vs. 14.3% vs. 16.7%, pâ¯=â¯0.97). CONCLUSIONS: ICAC is seen on CT in nearly three-quarters of patients with LVO-AIS. Extent of ICAC has a U-shaped association with successful reperfusion, in part due to more frequent use of rescue interventions in patients with extensive ICAC.
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The Stroke Treatment Academic Industry Roundtable XII included a workshop to discuss the most promising approaches to improve outcome from acute stroke. The workshop brought together representatives from academia, industry, and government representatives. The discussion examined approaches in 4 epochs: pre-reperfusion, reperfusion, post-reperfusion, and access to acute stroke interventions. The participants identified areas of priority for developing new and existing treatments and approaches to improve stroke outcomes. Although many advances in acute stroke therapy have been achieved, more work is necessary for reperfusion therapies to benefit the most possible patients. Prioritization of promising approaches should help guide the use of resources and investigator efforts.
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Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/terapia , Terapia Trombolítica , Acidente Vascular Cerebral/tratamento farmacológico , Trombectomia , Reperfusão , Resultado do TratamentoRESUMO
Increasing evidence indicates that circadian and diurnal rhythms robustly influence stroke onset, mechanism, progression, recovery, and response to therapy in human patients. Pioneering initial investigations yielded important insights but were often single-center series, used basic imaging approaches, and used conflicting definitions of key data elements, including what constitutes daytime versus nighttime. Contemporary methodologic advances in human neurovascular investigation have the potential to substantially increase understanding, including the use of large multicenter and national data registries, detailed clinical trial data sets, analysis guided by individual patient chronotype, and multimodal computed tomographic and magnetic resonance imaging. To fully harness the power of these approaches to enhance pathophysiologic knowledge, an important foundational step is to develop standardized definitions and coding guides for data collection, permitting rapid aggregation of data acquired in different studies, and ensuring a common framework for analysis. To meet this need, the Leducq Consortium International pour la Recherche Circadienne sur l'AVC (CIRCA) convened a Consensus Statement Working Group of leading international researchers in cerebrovascular and circadian/diurnal biology. Using an iterative, mixed-methods process, the working group developed 79 data standards, including 48 common data elements (23 new and 25 modified/unmodified from existing common data elements), 14 intervals for time-anchored analyses of different granularity, and 7 formal, validated scales. This portfolio of standardized data structures is now available to assist researchers in the design, implementation, aggregation, and interpretation of clinical, imaging, and population research related to the influence of human circadian/diurnal biology upon ischemic and hemorrhagic stroke.
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Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Coleta de Dados , Projetos de Pesquisa , Sistema de Registros , Biologia , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Many stroke recovery interventions are most beneficial when started 2-14d post-stroke, a time when patients become eligible for inpatient rehabilitation facilities (IRF) and neuroplasticity is often at its peak. Clinical trials focused on recovery need to expand the time from this plasticity to later outcome timepoints. METHODS: The disability course of patients with acute ischemic stroke (AIS) and intracranial hemorrhage (ICH) enrolled in Field Administration of Stroke Therapy Magnesium (FAST-MAG) Trial with moderate-severe disability (modified Rankin Scale [mRS] 3-5) on post-stroke day4 who were discharged to IRF 2-14d post-stroke were analyzed. RESULTS: Among 1422 patients, 446 (31.4%) were discharged to IRFs, including 23.6% within 2-14d and 7.8% beyond 14d. Patients with mRS 3-5 on day4 discharged to IRFs between 2-14d accounted for 21.7% (226/1041) of AIS patients and 28.9% (110/381) of ICH patients, (p < 0.001). Among these AIS patients, age was 69.8 (± 12.7), initial NIHSS median 8 (IQR 4-12), and day4 mRS = 3 in 16.4%, mRS = 4 in 50.0%, and mRS = 5 in 33.6%. Among these ICH patients, age was 62.4 (± 11.7), initial NIHSS median 9 (IQR 5-13), day 4 mRS = 3 in 9.4%, mRS = 4 in 45.3%, and mRS = 5 in 45.3% (p < 0.01 for AIS vs ICH). Between day4 to day90, mRS improved ≥ 1 levels in 72.6% of AIS patients vs 77.3% of ICH patients, p = 0.3. For AIS, mRS improved from mean 4.17 (± 0.7) to 2.84 (± 1.5); for ICH, mRS improved from mean 4.35 (± 0.7) to 2.75 (± 1.3). Patients discharged to IRF beyond day14 had less improvement on day90 mRS compared with patients discharged between 2-14d. CONCLUSIONS: In this acute stroke cohort, nearly 1 in 4 patients with moderate-severe disability on post-stroke day4 were transferred to IRF within 2-14d post-stroke. ICH patients had nominally greater mean improvement on mRS day90 than AIS patients. This course delineation provides a roadmap for future rehabilitation intervention studies.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/tratamento farmacológico , Hemorragias Intracranianas/epidemiologia , Alta do Paciente , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento , Ensaios Clínicos como AssuntoRESUMO
BACKGROUND: Prehospital automated large vessel occlusion (LVO) detection in Mobile Stroke Units (MSUs) could accelerate identification and treatment of patients with LVO acute ischemic stroke. Here, we evaluate the performance of a machine learning (ML) model on CT angiograms (CTAs) obtained from 2 MSUs to detect LVO. METHODS: Patients evaluated on MSUs in Houston and Los Angeles with out-of-hospital CTAs were identified. Anterior circulation LVO was defined as an occlusion of the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or anterior cerebral artery vessels and determined by an expert human reader. A ML model to detect LVO was trained and tested on independent data sets consisting of in-hospital CTAs and then tested on MSU CTA images. Model performance was determined using area under the receiver-operator curve statistics. RESULTS: Among 68 patients with out-of-hospital MSU CTAs, 40% had an LVO. The most common occlusion location was the middle cerebral artery M1 segment (59%), followed by the internal carotid artery (30%), and middle cerebral artery M2 (11%). Median time from last known well to CTA imaging was 88.0 (interquartile range, 59.5-196.0) minutes. After training on 870 in-hospital CTAs, the ML model performed well in identifying LVO in a separate in-hospital data set of 441 images with area under receiver-operator curve of 0.84 (95% CI, 0.80-0.87). ML algorithm analysis time was under 1 minute. The performance of the ML model on the MSU CTA images was comparable with area under receiver-operator curve 0.80 (95% CI, 0.71-0.89). There was no significant difference in performance between the Houston and Los Angeles MSU CTA cohorts. CONCLUSIONS: In this study of patients evaluated on MSUs in 2 cities, a ML algorithm was able to accurately and rapidly detect LVO using prehospital CTA acquisitions.
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AVC Isquêmico , Acidente Vascular Cerebral , Angiografia , Angiografia por Tomografia Computadorizada/métodos , Humanos , Aprendizado de Máquina , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND PURPOSE: We aimed to delineate the determinants of the initial speed of infarct progression and the association of speed of infarct progression (SIP) with procedural and functional outcomes. METHODS: From a prospectively maintained stroke center registry, consecutive anterior circulation ischemic stroke patients with large artery occlusion, National Institutes of Health Stroke Scale score ≥4, and multimodal vessel, ischemic core, and tissue-at-risk imaging within 24 hours of onset were included. Initial SIP was calculated as ischemic core volume at first imaging divided by the time from stroke onset to imaging. RESULTS: Among the 88 patients, SIP was median 2.2 cc/h (interquartile range, 0-8.7), ranging most widely within the first 6 hours after onset. Faster SIP was positively independently associated with a low collateral score (odds ratio [OR], 3.30 [95% CI, 1.25-10.49]) and arrival by emergency medical services (OR, 3.34 [95% CI, 1.06-10.49]) and negatively associated with prior ischemic stroke (OR, 0.12 [95% CI, 0.03-0.50]) and coronary artery disease (OR, 0.32 [95% CI, 0.10-1.00]). Among the 67 patients who underwent endovascular thrombectomy, slower SIP was associated with a shift to reduced levels of disability at discharge (OR, 3.26 [95% CI, 1.02-10.45]), increased substantial reperfusion by thrombectomy (OR, 8.30 [95% CI, 0.97-70.87]), and reduced radiological hemorrhagic transformation (OR, 0.34 [95% CI, 0.12-0.94]). CONCLUSIONS: Slower SIP is associated with a high collateral score, prior ischemic stroke, and coronary artery disease, supporting roles for both collateral robustness and ischemic preconditioning in fostering tissue resilience to ischemia. Among patients undergoing endovascular thrombectomy, the speed of infarct progression is a major determinant of clinical outcome.
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Isquemia Encefálica/diagnóstico por imagem , Progressão da Doença , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sistema de Registros , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Fatores de Tempo , Resultado do TratamentoRESUMO
Background and Purpose- Brain electrical stimulation, widely studied to facilitate recovery from stroke, has also been reported to confer direct neuroprotection in preclinical models of acute cerebral ischemia. Systematic review of controlled preclinical acute cerebral ischemia studies would aid in planning for initial human clinical trials. Methods- A systematic Medline search identified controlled, preclinical studies of central nervous system electrical stimulation in acute cerebral ischemia. Studies were categorized among 6 stimulation strategies. Three strategies applied different stimulation types to tissues within the ischemic zone (cathodal hemispheric stimulation [CHS], anodal hemispheric stimulation, and pulsed hemispheric stimulation), and 3 strategies applied deep brain stimulation to different neuronal targets remote from the ischemic zone (fastigial nucleus stimulation, subthalamic vasodilator area stimulation, and dorsal periaqueductal gray stimulation). Random-effects meta-analysis assessed electrical stimulation modification of final infarct volume. Study-level risk of bias and intervention-level readiness-for-translation were assessed using formal rating scales. Results- Systematic search identified 28 experiments in 21 studies, including a total of 350 animals, of electrical stimulation in preclinical acute cerebral ischemia. Overall, in animals undergoing electrical stimulation, final infarct volumes were reduced by 37% (95% CI, 34%-40%; P<0.001), compared with control. There was evidence of heterogeneity of efficacy among stimulation strategies (I2=93.1%, Pheterogeneity<0.001). Among the within-ischemic zone stimulation strategies, only CHS significantly reduced the infarct volume (27 %; 95% CI, 22%-33%; P<0.001); among the remote-from ischemic zone approaches, all (fastigial nucleus stimulation, subthalamic vasodilator area stimulation, and dorsal periaqueductal gray stimulation) reduced infarct volumes by approximately half. On formal rating scales, CHS studies had the lowest risk of bias, and CHS had the highest overall quality of intervention-level evidence supporting readiness to proceed to clinical testing. Conclusions- Electrical stimulation reduces final infarct volume across preclinical studies. CHS shows the most robust evidence and is potentially appropriate for progression to early-stage human clinical trial testing as a promising neuroprotective intervention.
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Isquemia Encefálica/patologia , Estimulação Elétrica/métodos , Acidente Vascular Cerebral/patologia , Animais , Modelos Animais de Doenças , CamundongosRESUMO
BACKGROUND: Telestroke is an efficient, cost-effective way to standardize care and improve access to immediate neurologic expertise for rural hospitals and other underserved areas. Hands-free wearable technology potentially allows for faster evaluations that fit easily within prehospital workflows and could improve prehospital triage of stroke patients to appropriate receiving stroke centers. The goal of this study is to assess the feasibility and inter-rater reliability of wearable eyeglass video technology in assessing stroke-related neurologic deficits in patients with suspected acute stroke. METHODS: Consecutive patients with suspected stroke were evaluated concurrently by an on-site neurologist using wearable eyeglass video technology and a remotely located neurologist viewing the patient through an online platform. Inter-rater reliability in assigning National Institutes of Health Stroke Scale (NIHSS) scores was evaluated using inter-rater correlation coefficient (ICC) and weighted kappa scores. RESULTS: Among 17 enrolled patients, mean age was 58 (SD ± 20) and 29% were female. There was a high degree of correlation in total NIHSS score (ICC .99 and weighted kappa .88) and across all NIHSS subitems (ICC .81-1 and weighted kappa .68-1) between the examiner evaluating remotely via wearable eyeglass video technology with access to the patient and the in-person examiner. The maximum difference between the 2 NIHSS scores was 3. CONCLUSIONS: The use of wearable eyeglass video technology in telestroke is feasible and reliable. Use of this technology in the prehospital setting has the potential to improve early assessment of patients with acute stroke symptoms and to facilitate transfer to appropriate stroke centers in the regional systems of care.
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Avaliação da Deficiência , Consulta Remota/instrumentação , Óculos Inteligentes , Acidente Vascular Cerebral/diagnóstico , Comunicação por Videoconferência/instrumentação , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Fluxo de TrabalhoRESUMO
BACKGROUND AND PURPOSE: Impaired cerebrovascular reserve in chronic steno-occlusive disease has been shown to be associated with poor leptomeningeal collaterals (LMCs) on digital subtraction angiography and increased stroke risk. We examined the relationship between the degree of LMCs and the flow change with Diamox challenge measured using quantitative magnetic resonance angiography (QMRA). METHODS: Patients with steno-occlusion in the internal carotid artery or middle cerebral artery (MCA) at our institution between 2007 and 2013 were retrospectively studied. Intracranial flows were obtained using QMRA, and flow change with Diamox (QMRAΔd) was calculated as follows: ([flow after Diamox-flow before Diamox]/[flow before Diamox])×100%. Poor LMC was defined as grade 1 or 2, and robust LMC was defined as grade 3 or 4 based on the ASITN/SIR (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology) grading system on digital subtraction angiography. RESULTS: Thirty-eight patients had angiographic and flow data. Ipsilateral MCA QMRAΔd was significantly lower versus the contralateral side (flow, 85.5 versus 135.9 mL/min; P<0.001 and QMRAΔd, 24.0% versus 45.6%; P=0.01). If LMCs were robust (n=12), MCA QMRAΔd was significantly higher (21.4% versus -26.8%; P=0.04) compared with patients with poor LMC (n=4). CONCLUSIONS: We show that patients with more robust LMC have better MCA QMRAΔd. Therefore, QMRAΔd may be used for the functional assessment of LMC as a surrogate for cerebrovascular reserve in chronic internal carotid artery or MCA steno-occlusive disease.
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Acetazolamida , Inibidores da Anidrase Carbônica , Doenças das Artérias Carótidas/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Circulação Colateral/fisiologia , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodos , Meninges/irrigação sanguínea , Idoso , Biomarcadores , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Importance: Cathodal transcranial direct current stimulation (C-tDCS) provides neuroprotection in preclinical models of acute ischemic stroke (AIS) by inhibiting peri-infarct excitotoxic effects and enhancing collateral perfusion due to its vasodilatory properties. Objective: To report the first-in-human pilot study using individualized high-definition (HD) C-tDCS as a treatment of AIS. Design, Setting, and Participants: This randomized clinical trial was sham controlled with 3 + 3 dose escalation design, and was conducted at a single center from October 2018 to July 2021. Eligible participants were treated for AIS within 24 hours from onset, had imaging evidence of cortical ischemia with salvageable penumbra, and were ineligible for reperfusion therapies. HD C-tDCS electrode montage was selected for each patient to deliver the electric current to the ischemic region only. Patients were followed for 90 days. Main Outcomes and Measures: Primary outcomes were feasibility, assessed as time from randomization to study stimulation initiation; tolerability, assessed by rate of patients completing the full study stimulation period; and safety, assessed by rates of symptomatic intracranial hemorrhage at 24 hours. The efficacy imaging biomarkers of neuroprotection and collateral enhancement were explored. Results: A total of 10 patients with AIS were enrolled, 7 were randomized to active treatment and 3 to sham. Patient age was mean (SD) 75 (10) years old, 6 (60%) were female, and National Institutes of Health Stroke Scale score was mean (SD) 8 (7). Two doses of HD C-tDCS (1 milliamp [mA] for 20 minutes and 2 mA for 20 minutes) were studied. The speed of HD C-tDCS implementation was a median (IQR) 12.5 minutes (9-15 minutes) in the last 4 patients. Patients tolerated the HD C-tDCS with no permanent stimulation cessation. The hypoperfused region was reduced by a median (IQR) 100% (46% to 100%) in the active group vs increased by 325% (112% to 412%) in sham. Change in quantitative relative cerebral blood volume early poststimulation was a median (IQR) 64% (40% to 110%) in active vs -4% (-7% to 1%) sham patients and followed a dose-response pattern. Penumbral salvage in the active C-tDCS group was median (IQR) 66% (29% to 80.5%) vs 0% (IQR 0% to 0%) in sham. Conclusion and Relevance: In this randomized, first-in-human clinical trial, HD C-tDCS was started efficiently and well tolerated in emergency settings, with signals of beneficial effect upon penumbral salvage. These results support advancing HD C-tDCS to larger trials. Trial Registration: ClinicalTrials.gov Identifier: NCT03574038.
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AVC Isquêmico , Estimulação Transcraniana por Corrente Contínua , Estados Unidos , Humanos , Feminino , Idoso , Masculino , Estimulação Transcraniana por Corrente Contínua/efeitos adversos , Estimulação Transcraniana por Corrente Contínua/métodos , AVC Isquêmico/etiologia , Projetos Piloto , Terapia CombinadaRESUMO
BACKGROUND: Infarct growth on multimodal imaging is a common lead outcome in phase 2 proof-of-concept and dose-optimization neuroprotective agent stroke trials. However, the effect size in infarct growth reduction that correlates with clinically meaningful differences in clinical global disability outcomes has not been well delineated. METHODS: A systematic literature search identified all endovascular thrombectomy randomized trials reporting magnitude of treatment effect on both infarct growth reduction and increase in functional independence (modified Rankin Scale (mRS) 0-2). Data aggregation determined the size of infarct growth reductions salient to four types of clinically meaningful effect sizes of increase in functional independence: (1) the minimal clinically important difference (MCID)-outcome specific; (2) the MCID-practice changing; (3) the realistic target difference; and (4) the reasonable comparability effect size. RESULTS: A systematic search identified four trials enrolling 612 imaged participants. Across the trials, the amount of functional independence (mRS 0-2) increase associated with each 1 mL reduction in infarct growth was mean 2.3±0.6%. An infarct growth reduction of 0.57 mL correlated with the mRS 0-2 increase MCID of 1.3%. Infarct growth reductions of 2.27 mL, 4.35 mL, and 6.53 mL correlated with realistic effect and reasonable comparability effects sizes of mRS 0-2 increases of 5%, 10%, and 15%, respectively. CONCLUSION: In formal meta-analysis of randomized treatment trials, every 1 mL reduction in infarct growth was associated with a 2.3% increase in functional independence (mRS 0-2) at 3 months. This conversion factor can inform selection of infarct growth effect size targets for phase 2 trials of neuroprotective agents.
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BACKGROUND AND PURPOSE: Perfusion-based collateral indices such as the perfusion collateral index and the hypoperfusion intensity ratio have shown promise in the assessment of collaterals in patients with acute ischemic stroke. We aimed to compare the diagnostic performance of the perfusion collateral index and the hypoperfusion intensity ratio in collateral assessment compared with angiographic collaterals and outcome measures, including final infarct volume, infarct growth, and functional independence. MATERIALS AND METHODS: Consecutive patients with acute ischemic stroke with anterior circulation proximal arterial occlusion who underwent endovascular thrombectomy and had pre- and posttreatment MRI were included. Using pretreatment MR perfusion, we calculated the perfusion collateral index and the hypoperfusion intensity ratio for each patient. The angiographic collaterals obtained from DSA were dichotomized to sufficient (American Society of Interventional and Therapeutic Neuroradiology [ASITN] scale 3-4) versus insufficient (ASITN scale 0-2). The association of collateral status determined by the perfusion collateral index and the hypoperfusion intensity ratio was assessed against angiographic collaterals and outcome measures. RESULTS: A total of 98 patients met the inclusion criteria. Perfusion collateral index values were significantly higher in patients with sufficient angiographic collaterals (P < .001), while there was no significant (P = .46) difference in hypoperfusion intensity ratio values. Among patients with good (mRS 0-2) versus poor (mRS 3-6) functional outcome, the perfusion collateral index of ≥ 62 was present in 72% versus 31% (P = .003), while the hypoperfusion intensity ratio of ≤0.4 was present in 69% versus 56% (P = .52). The perfusion collateral index and the hypoperfusion intensity ratio were both significantly predictive of final infarct volume, but only the perfusion collateral index was significantly (P = .03) associated with infarct growth. CONCLUSIONS: Results show that the perfusion collateral index outperforms the hypoperfusion intensity ratio in the assessment of collateral status, infarct growth, and determination of functional outcomes.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/terapia , Imageamento por Ressonância Magnética/métodos , Trombectomia , Perfusão , Infarto , Circulação Colateral , Isquemia Encefálica/terapiaRESUMO
BACKGROUND: Application of machine learning (ML) algorithms has shown promising results in estimating ischemic core volumes using non-contrast CT (NCCT). OBJECTIVE: To assess the performance of the e-Stroke Suite software (Brainomix) in assessing ischemic core volumes on NCCT compared with CT perfusion (CTP) in patients with acute ischemic stroke. METHODS: In this retrospective multicenter study, patients with anterior circulation large vessel occlusions who underwent pretreatment NCCT and CTP, successful reperfusion (modified Thrombolysis in Cerbral Infarction ≥2b), and post-treatment MRI, were included from three stroke centers. Automated calculation of ischemic core volumes was obtained on NCCT scans using ML algorithm deployed by e-Stroke Suite and from CTP using Olea software (Olea Medical). Comparative analysis was performed between estimated core volumes on NCCT and CTP and against MRI calculated final infarct volume (FIV). RESULTS: A total of 111 patients were included. Estimated ischemic core volumes (mean±SD, mL) were 20.4±19.0 on NCCT and 19.9±18.6 on CTP, not significantly different (P=0.82). There was moderate (r=0.40) and significant (P<0.001) correlation between estimated core on NCCT and CTP. The mean difference between FIV and estimated core volume on NCCT and CTP was 29.9±34.6 mL and 29.6±35.0 mL, respectively (P=0.94). Correlations between FIV and estimated core volume were similar for NCCT (r=0.30, P=0.001) and CTP (r=0.36, P<0.001). CONCLUSIONS: Results show that ML-based estimated ischemic core volumes on NCCT are comparable to those obtained from concurrent CTP in magnitude and in degree of correlation with MR-assessed FIV.
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Many neuroprotective and other therapies for treatment of acute ischemic stroke have failed in translation to human studies, indicating a need for more rigorous, multidimensional quality assessment of the totality of preclinical evidence supporting a therapy prior to conducting human trials. A consensus panel of stroke preclinical model and human clinical trial experts assessed candidate items for the translational readiness scale, compiled from prior instruments (STAIR, ARRIVE, CAMARADES, RoB 2) based on importance, reliability, and feasibility. Once constructed, the tool was applied by two independent raters to four current candidate acute stroke therapies, including two pharmacologic agents [nerinetide and trans-sodium crocetinate] and two device interventions [cathodal transcranial direct current stimulation and fastigial nucleus stimulation]. The Preclinical evidence of Readiness In stroke Models Evaluating Drugs and Devices (PRIMED2) assessment tool rates the totality of evidence available from all reported preclinical animal stroke model studies in 11 domains related to diversity of tested animals, time windows, feasibility of agent route of delivery, and robustness of effect magnitude. Within each content domain, clearly operationalized rules assign strength of evidence ratings of 0-2. When applied to the four assessed candidate agents, inter-rater reliability was high (kappa = 0.88), and each agent showed a unique profile of evidentiary strengths and weaknesses. The PRIMED2 assessment tool provides a multidimensional assessment of the cumulative preclinical evidence for a candidate acute stroke therapy on factors judged important for successful basic-to-clinical translation. Further evaluation and refinement of this tool is desirable to improve successful translation of therapies for acute stroke.
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Isquemia Encefálica , AVC Isquêmico , Fármacos Neuroprotetores , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Animais , Isquemia Encefálica/tratamento farmacológico , Modelos Animais de Doenças , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
BACKGROUND: The potential heterogeneity in occlusive thrombi caused by in situ propagation by secondary thrombosis after embolic occlusion could obscure the characteristics of original thrombi, preventing the clarification of a specific thrombus signature for the etiology of ischemic stroke. We aimed to investigate the heterogeneity of occlusive thrombi by pretreatment imaging. METHODS: Among consecutive stroke patients with acute embolic anterior circulation large vessel occlusion treated with thrombectomy, we retrospectively reviewed 104 patients with visible occlusive thrombi on pretreatment non-contrast computed tomography admitted from January 2015 to December 2018. A region of interest was set on the whole thrombus on non-contrast computed tomography under the guidance of computed tomography angiography. The region of interest was divided equally into the proximal and distal segments and the difference in Hounsfield unit densities between the two segments was calculated. RESULTS: Hounsfield unit density in the proximal segment was higher than that in the distal segment (mean difference 4.45; p < 0.001), regardless of stroke subtypes. On multivariate analysis, thrombus length was positively correlated (ß = 0.25; p < 0.001) and time from last-known-well to imaging was inversely correlated (ß = -0.0041; p = 0.002) with the difference in Hounsfield unit densities between the proximal and distal segments. CONCLUSIONS: The difference in density between the proximal and distal segments increased as thrombi became longer and decreased as thrombi became older after embolic occlusion. This time/length-dependent thrombus heterogeneity between the two segments is suggestive of secondary thrombosis initially occurring on the proximal side of the occlusion.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Trombectomia/métodos , Trombose/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The ubiquitous vascular response to transcranial electrical stimulation (tES) has been attributed to the secondary effect of neuronal activity forming the classic neurovascular coupling. However, the current density delivered transcranially concentrates in: A) the cerebrospinal fluid of subarachnoid space where cerebral vasculature resides after reaching the dural and pial surfaces and B) across the blood-brain-barrier after reaching the brain parenchyma. Therefore, it is anticipated that tES has a primary vascular influence. OBJECTIVES: Focused review of studies that demonstrated the direct vascular response to electrical stimulation and studies demonstrating evidence for tES-induced vascular effect in coupled neurovascular systems. RESULTS: tES induces both primary and secondary vascular phenomena originating from four cellular elements; the first two mediating a primary vascular phenomenon mainly in the form of an immediate vasodilatory response and the latter two leading to secondary vascular effects and as parts of classic neurovascular coupling: 1) The perivascular nerves of more superficially located dural and pial arteries and medium-sized arterioles with multilayered smooth muscle cells; and 2) The endothelial lining of all vessels including microvasculature of blood-brain barrier; 3) Astrocytes; and 4) Neurons of neurovascular units. CONCLUSION: A primary vascular effect of tES is highly suggested based on various preclinical and clinical studies. We explain how the nature of vascular response can depend on vessel anatomy (size) and physiology and be controlled by stimulation waveform. Further studies are warranted to investigate the mechanisms underlying the vascular response and its contribution to neural activity in both healthy brain and pathological conditions - recognizing many brain diseases are associated with alteration of cerebral hemodynamics and decoupling of neurovascular units.
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Acoplamento Neurovascular , Estimulação Transcraniana por Corrente Contínua , Arteríolas , Astrócitos , EncéfaloRESUMO
BACKGROUND: Targeted eloquence-based tissue reperfusion within the primary motor cortex may have a differential effect on disability as compared with traditional volume-based (thrombolysis in cerebral infarction, TICI) reperfusion after endovascular thrombectomy (EVT) in the setting of acute ischemic stroke (AIS). METHODS: We explored the impact of eloquent reperfusion (ER) within primary motor cortex (PMC) on clinical outcome (modified Rankin Scale, mRS) in AIS patients undergoing EVT. ER-PMC was defined as presence of flow on final digital subtraction angiography (DSA) within four main cortical branches, supplying the PMC (middle cerebral artery (MCA) - precentral, central, postcentral; anterior cerebral artery (ACA) - medial frontal branch arising from callosomarginal or pericallosal arteries) and graded as absent (0), partial (1), and complete (2). Prospectively collected data from two centers were analyzed. Multivariate analysis was conducted to assess the impact of ER-PMC on 90-day disability (mRS) among patients with anterior circulation occlusion who achieved partial reperfusion (TICI 2a and 2b). RESULTS: Among the 125 patients who met the study criteria, ER-PMC distribution was: absent (0) in 19/125 (15.2%); partial (1) in 52/125 (41.6%), and complete (2) in 54/125 (43.2%). TICI 2b was achieved in 102/125 (81.6%) and ER-PMC was substantially higher in those patients (P<0.001). In multivariate analysis, in addition to age and symptomatic intracranial hemorrhage, ER-PMC had a profound independent impact on 90-day disability (OR 6.10, P=0.001 for ER-PMC 1 vs 0 and OR 9.87, P<0.001 for ER-PMC 2 vs 0), while the extent of total partial reperfusion (TICI 2b vs 2a) was not related to 90-day mRS. CONCLUSIONS: Eloquent PMC-tissue reperfusion is a key determinant of functional outcome, with a greater impact than volume-based (TICI) degree of partial reperfusion alone. PMC-targeted revascularization among patients with partial reperfusion may further diminish post-stroke disability after EVT.
Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Córtex Motor , Acidente Vascular Cerebral , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/cirurgia , Humanos , Córtex Motor/diagnóstico por imagem , Reperfusão , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia , Terapia Trombolítica , Resultado do TratamentoRESUMO
BACKGROUND: Sphenopalatine ganglion stimulation (SPG-Stim) for ischemic stroke, starting 8-24 h after onset and continuing through five days in a pooled analysis of two recent, randomized, sham-controlled trials, improved outcome of acute ischemic stroke patients with confirmed cortical involvement. As a neuromodulatory therapy, SPG-Stim differs substantially from existing pharmacologic (lytic and antiplatelets) and device (endovascular thrombectomy) acute ischemic stroke treatments. AIM: Focused review of SPG anatomy, physiology, and neurovascular and neurobiologic mechanisms of action mediating benefit of SPG-Stim in acute ischemic stroke. SUMMARY OF REVIEW: Located posterior to the maxillary sinus, the SPG is the main source of parasympathetic innervation to the anterior circulation. Preclinical and human studies delineate four distinct mechanisms of action by which the SPG-Stim may confer benefit in acute ischemic stroke: (1) collateral vasodilation and enhanced cerebral blood flow, mediated by release of neurotransmitters with vasodilatory effects, nitric oxide, and acetylcholine, (2) stimulation frequency- and intensity-dependent stabilization of the blood-brain barrier, reducing edema (3) direct acute neuroprotection from activation of the central cholinergic system with resulting anti-inflammatory, anti-apoptotic, and anti-excitatory effects; and (4) neuroplasticity enhancement from enhanced central cholinergic and adrenergic neuromodulation of cortical networks and nitrous oxide release stimulating neurogenesis. CONCLUSION: The benefit of SPG-Stim in acute ischemic stroke is likely conferred not only by potent collateral augmentation, but also blood-barrier stabilization, direct neuroprotection, and neuroplasticity enhancement. Further studies clarifying the relative contribution of these mechanisms and the stimulation protocols that maximize each may help optimize SPG-Stim as a therapy for acute ischemic stroke.
Assuntos
Isquemia Encefálica , Gânglios Parassimpáticos , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/terapia , Circulação Cerebrovascular , Humanos , Acidente Vascular Cerebral/terapiaRESUMO
Neuroimaging provides detailed information regarding the hemodynamic, metabolic and cellular parameters of cerebral ischemia (CI). Although providing just a snapshot in time, it assists in delineating the boundaries and extent of this continually evolving process, from the irreversibly damaged infarct core to the penumbral tissue, where salvage via reperfusion has been the focus of acute stroke therapies. Beyond the extent of the ischemic lesion, neuroimaging elucidates the topography and underlying mechanism of CI. Finally, based on the pathophysiological information, neuroimaging assists in the selection of optimal therapeutic strategies, from hyperacute to chronic phases of CI. Here we review different neuroimaging techniques by which the pathophysiology of cerebral ischemia can be delineated. This article is part of the Special Issue entitled 'Cerebral Ischemia'.