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1.
Circ Res ; 134(6): 770-790, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38484031

RESUMO

Time-of-day significantly influences the severity and incidence of stroke. Evidence has emerged not only for circadian governance over stroke risk factors, but also for important determinants of clinical outcome. In this review, we provide a comprehensive overview of the interplay between chronobiology and cerebrovascular disease. We discuss circadian regulation of pathophysiological mechanisms underlying stroke onset or tolerance as well as in vascular dementia. This includes cell death mechanisms, metabolism, mitochondrial function, and inflammation/immunity. Furthermore, we present clinical evidence supporting the link between disrupted circadian rhythms and increased susceptibility to stroke and dementia. We propose that circadian regulation of biochemical and physiological pathways in the brain increase susceptibility to damage after stroke in sleep and attenuate treatment effectiveness during the active phase. This review underscores the importance of considering circadian biology for understanding the pathology and treatment choice for stroke and vascular dementia and speculates that considering a patient's chronotype may be an important factor in developing precision treatment following stroke.


Assuntos
Relógios Circadianos , Demência Vascular , Acidente Vascular Cerebral , Humanos , Ritmo Circadiano , Sono/fisiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Relógios Circadianos/fisiologia
2.
Clin Med (Lond) ; 23(3): 219-227, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37236792

RESUMO

This narrative review provides an overview of the posterior circulation and the clinical features of common posterior circulation stroke (PCS) syndromes in the posterior arterial territories and how to distinguish them from mimics. We outline the hyperacute management of patients with suspected PCS with emphasis on how to identify those who are likely to benefit from intervention based on imaging findings. Finally, we review advances in treatment options, including developments in endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT), and the principles of medical management and indications for neurosurgery. Observational and randomised clinical trial data have been equivocal regarding EVT in PCS, but more recent studies strongly support its efficacy. There have been concomitant advances in imaging of posterior stroke to guide optimal patient selection for thrombectomy. Recent evidence suggests that clinicians should have a heightened suspicion of posterior circulation events with the resultant implementation of timely, evidence-based management.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/complicações , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Isquemia Encefálica/complicações , Procedimentos Endovasculares/métodos , Trombectomia/métodos , AVC Isquêmico/complicações , Resultado do Tratamento , Terapia Trombolítica/métodos
3.
Emerg Med J ; 38(1): 33-39, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33172878

RESUMO

BACKGROUND: Mechanical thrombectomy (MT) is a time-sensitive emergency procedure for patients who had ischaemic stroke leading to improved health outcomes. Health systems need to ensure that MT is delivered to as many patients as quickly as possible. Using decision modelling, we aimed to evaluate the cost-effectiveness of secondary transfer by helicopter emergency medical services (HEMS) compared with ground emergency medical services (GEMS) of rural patients eligible for MT in England. METHODS: The model consisted of (1) a short-run decision tree with two branches, representing secondary transfer transportation strategies and (2) a long-run Markov model for a theoretical population of rural patients with a confirmed ischaemic stroke. Strategies were compared by lifetime costs: quality-adjusted life years (QALYs), incremental cost per QALY gained and net monetary benefit. Sensitivity and scenario analyses explored uncertainty around parameter values. RESULTS: We used the base case of early-presenting (<6 hours to arterial puncture) patient aged 75 years who had stroke to compare HEMS and GEMS. This produced an incremental cost-effectiveness ratio (ICER) of £28 027 when a 60 min reduction in travel time was assumed. Scenario analyses showed the importance of the reduction in travel time and futile transfers in lowering ICERs. For late presenting (>6 hours to arterial puncture), ground transportation is the dominant strategy. CONCLUSION: Our model indicates that using HEMS to transfer patients who had stroke eligible for MT from remote hospitals in England may be cost-effective when: travel time is reduced by at least 60 min compared with GEMS, and a £30 000/QALY threshold is used for decision-making. However, several other logistic considerations may impact on the use of air transportation.


Assuntos
Resgate Aéreo/economia , Transferência de Pacientes/economia , Acidente Vascular Cerebral/cirurgia , Trombectomia/economia , Idoso , Aeronaves , Árvores de Decisões , Inglaterra , Feminino , Humanos , Masculino , Cadeias de Markov , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida
4.
Clin Med (Lond) ; 20(3): e40-e45, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32414740

RESUMO

INTRODUCTION: The clinical efficacy and cost-effectiveness of mechanical thrombectomy (MT) for the treatment of large vessel occlusion stroke is well established, but uncertainty remains around the true cost of delivering this treatment within the NHS. The aim of this study was to establish the cost of providing MT within the hyperacute phase of care and to explore differences in resources used and costs across different neuroscience centres in the UK. METHOD: This was a multicentre retrospective study using micro-costing methods to enable a precise assessment of the costs of MT from an NHS perspective. Data on resources used and their costs were collected from five UK neuroscience centres between 2015 and 2018. RESULTS: Data were collected on 310 patients with acute ischaemic stroke treated with MT. The mean total cost of providing MT and inpatient care within 24 hours was £10,846 (95% confidence interval (CI) 10,527-11,165) per patient. The main driver of cost was MT procedure costs, accounting for 73% (£7,943; 95% CI 7,649-8,237) of the total 24-hour cost. Costs were higher for patients treated under general anaesthesia (£11,048; standard deviation (SD) 2,654) than for local anaesthesia (£9,978; SD 2,654), mean difference £1,070 (95% CI 381-1,759; p=0.003); admission to an intensive care unit (ICU; £12,212; SD 3,028) against for admission elsewhere (£10,179; SD 2,415), mean difference £2,032 (95% CI 1,345-2,719; p<0001).The mean cost within 72 hours was £12,440 (95% CI 10,628-14,252). The total costs for the duration of inpatient care before discharge from a thrombectomy centre was £14,362 (95% CI 13,603-15,122). CONCLUSIONS: Major factors contributing to costs of MT for stroke include consumables and staff for intervention, use of general anaesthesia and ICU admissions. These findings can inform the reimbursement, provision and strategic planning of stroke services and aid future economic evaluations.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Isquemia Encefálica/cirurgia , Humanos , Estudos Retrospectivos , Medicina Estatal , Acidente Vascular Cerebral/terapia , Trombectomia , Reino Unido
5.
BMC Health Serv Res ; 19(1): 821, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703684

RESUMO

BACKGROUND: We have previously modelled that the optimal number of comprehensive stroke centres (CSC) providing endovascular thrombectomy (EVT) in England would be 30 (net 6 new centres). We now estimate the relative effectiveness and cost-effectiveness of increasing the number of centres from 24 to 30. METHODS: We constructed a discrete event simulation (DES) to estimate the effectiveness and lifetime cost-effectiveness (from a payer perspective) using 1 year's incidence of stroke in England. 2000 iterations of the simulation were performed comparing baseline 24 centres to 30. RESULTS: Of 80,800 patients admitted to hospital with acute stroke/year, 21,740 would be affected by the service reconfiguration. The median time to treatment for eligible early presenters (< 270 min since onset) would reduce from 195 (IQR 155-249) to 165 (IQR 105-224) minutes. Our model predicts reconfiguration would mean an additional 33 independent patients (modified Rankin scale [mRS] 0-1) and 30 fewer dependent/dead patients (mRS 3-6) per year. The net addition of 6 centres generates 190 QALYs (95%CI - 6 to 399) and results in net savings to the healthcare system of £1,864,000/year (95% CI -1,204,000 to £5,017,000). The estimated budget impact was a saving of £980,000 in year 1 and £7.07 million in years 2 to 5. CONCLUSION: Changes in acute stroke service configuration will produce clinical and cost benefits when the time taken for patients to receive treatment is reduced. Benefits are highly likely to be cost saving over 5 years before any capital investment above £8 million is required.


Assuntos
Procedimentos Endovasculares/economia , Acidente Vascular Cerebral/economia , Trombectomia/economia , Idoso , Instituições de Assistência Ambulatorial/economia , Orçamentos , Análise Custo-Benefício , Atenção à Saúde/economia , Inglaterra , Feminino , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Medicina Estatal/economia , Acidente Vascular Cerebral/terapia , Trombectomia/métodos , Tempo para o Tratamento , Resultado do Tratamento
6.
BMC Health Serv Res ; 18(1): 135, 2018 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-29471828

RESUMO

BACKGROUND: Intra-arterial thrombectomy is the gold standard treatment for large artery occlusive stroke. However, the evidence of its benefits is almost entirely based on trials delivered by experienced neurointerventionists working in established teams in neuroscience centres. Those responsible for the design and prospective reconfiguration of services need access to a comprehensive and complementary array of information on which to base their decisions. This will help to ensure the demonstrated effects from trials may be realised in practice and account for regional/local variations in resources and skill-sets. One approach to elucidate the implementation preferences and considerations of key experts is a Delphi survey. In order to support commissioning decisions, we aimed using an electronic Delphi survey to establish consensus on the options for future organisation of thrombectomy services among physicians with clinical experience in managing large artery occlusive stroke. METHODS: A Delphi survey was developed with 12 options for future organisation of thrombectomy services in England. A purposive sampling strategy established an expert panel of stroke physicians from the British Association of Stroke Physicians (BASP) Clinical Standards and/or Executive Membership that deliver 24/7 intravenous thrombolysis. Options with aggregate scores falling within the lowest quartile were removed from the subsequent Delphi round. Options reaching consensus following the two Delphi rounds were then ranked in a final exercise by both the wider BASP membership and the British Society of Neuroradiologists (BSNR). RESULTS: Eleven stroke physicians from BASP completed the initial two Delphi rounds. Three options achieved consensus, with subsequently wider BASP (97%, n = 43) and BSNR members (86%, n = 21) assigning the highest approval rankings in the final exercise for transferring large artery occlusive stroke patients to nearest neuroscience centre for thrombectomy based on local CT/CT Angiography. CONCLUSIONS: The initial Delphi rounds ensured optimal reduction of options by an expert panel of stroke physicians, while subsequent ranking exercises allowed remaining options to be ranked by a wider group of experts within stroke to reach consensus. The preferred implementation option for thrombectomy is investigating suspected acute stroke patients by CT/CT Angiography and secondary transfer of large artery occlusive stroke patients to the nearest neuroscience (thrombectomy) centre.


Assuntos
Acidente Vascular Cerebral/terapia , Trombectomia , Consenso , Técnica Delphi , Inglaterra , Previsões , Pesquisa sobre Serviços de Saúde , Humanos , Estudos Prospectivos , Inquéritos e Questionários
7.
Int J Stroke ; 13(4): 348-361, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29171362

RESUMO

Endovascular mechanical thrombectomy (MT) for the treatment of acute stroke due to large vessel occlusion has evolved significantly with the publication of multiple positive thrombectomy trials. MT is now a recommended treatment for acute ischemic stroke. Mechanical thrombectomy is associated with a number of intra-procedural or post-operative complications, which need to be minimized and effectively managed to maximize the benefits of thrombectomy. Procedural complications include: access-site problems (vessel/nerve injury, access-site hematoma and groin infection); device-related complications (vasospasm, arterial perforation and dissection, device detachment/misplacement); symptomatic intracerebral hemorrhage; subarachnoid hemorrhage; embolization to new or target vessel territory. Other complications include: anesthetic/contrast-related, post-operative hemorrhage, extra-cranial hemorrhage and pseudoaneurysm. Some complications are life-threatening and many lead to increased length of stay in intensive care and stroke units. Complications increase costs and delay the commencement of rehabilitation. Some may be preventable; the impact of others can be minimized with early detection and appropriate management. Both neurointerventionists and stroke specialists need to be aware of the risk factors, strategies for prevention, and management of these complications. With the increasing use of mechanical thrombectomy for the treatment of acute ischemic stroke, incidence and outcome of complications will need to be carefully monitored by stroke teams. In this narrative review, we examine the frequency of complications of MT in the treatment of acute ischemic stroke with an emphasis on periprocedural complications. Overall, from recent randomized controlled trials, the risk of complications with sequelae for patient from mechanical thrombectomy is ∼15%. We discuss the management of complications and identify areas with limited evidence, which need further research. Search strategy and selection criteria Relevant evidence was found by searches of Medline and Cochrane Library, reference list, cross-referencing and main journal content pages. Search terms included "brain ischemia", "acute ischemic stroke", "cerebral infarction" AND "mechanical thrombectomy", "endovascular therapy", "endovascular treatment", "endovascular embolectomy", "intra-arterial" AND "randomized controlled trial", "non-randomised trials", "observational studies" AND "complications", "procedural complications", "peri-procedural complications", "device-related complications", "management", "treatment", "outcome". The search included only human studies, and was limited to studies published in English between January 2014 and November 2016. The final reference list was selected on the basis of relevance to the topics covered in the Review. Guidelines for management of acute ischaemic stroke by the American Heart Association, the European Stroke Organisation, multi-disciplinary guidelines and the National Institute for Health and Care Excellence (NICE) were also reviewed.


Assuntos
Isquemia Encefálica/terapia , Procedimentos Endovasculares/efeitos adversos , Trombólise Mecânica/efeitos adversos , Acidente Vascular Cerebral/terapia , Artérias/lesões , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/prevenção & controle , Ensaios Clínicos como Assunto , Humanos , Embolia Intracraniana/etiologia , Embolia Intracraniana/prevenção & controle , Complicações Intraoperatórias/etiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Falha de Prótese/efeitos adversos , Punções/efeitos adversos , Doses de Radiação , Ensaios Clínicos Controlados Aleatórios como Assunto , Stents/efeitos adversos , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/prevenção & controle , Dispositivos de Oclusão Vascular/efeitos adversos , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/prevenção & controle
8.
Eur Stroke J ; 2(4): 308-318, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31008323

RESUMO

PURPOSE: Intra-arterial mechanical thrombectomy combined with appropriate patient selection (image-based selection of acute ischaemic stroke patients with large artery occlusion) yields improved clinical outcomes. We conducted a systematic review and meta-analysis, with trial sequential analysis to understand the benefits, risks and impact of new trials reporting in 2016 on the magnitude/certainty of the estimates for clinical effectiveness and safety of mechanical thrombectomy. METHOD: Random effects' models were conducted of randomised clinical trials comparing mechanical thrombectomy (stent retriever or aspiration devices) with/without adjuvant intravenous thrombolysis with intravenous thrombolysis and other forms of best medical/supportive care in the treatment of acute ischaemic stroke. Study inclusion and risk of bias were assessed independently by two reviewers. Functional independence (modified Rankin Scale 0-2) and mortality at 90 days, including symptomatic intracranial haemorrhage rate were extracted. Trial sequential analysis established the strength of the evidence derived from the meta-analyses. FINDINGS: Eight trials of mechanical thrombectomy with a total sample size of 1841 (916 patients treated with mechanical thrombectomy and 925 treated without mechanical thrombectomy) fulfilled review inclusion criteria. The three most recent trials more precisely defined the effectiveness of mechanical thrombectomy (modified Rankin Scale 0 to 2; OR = 2.07, 95% CI = 1.70 to 2.51 based on data from eight trials versus OR = 2.39, 95% CI = 1.88 to 3.04 based on data from five trials). Meta-analyses showed no effect on mortality (OR = 0.81, 95% CI = 0.61 to 1.07) or symptomatic intracranial haemorrhage (OR = 1.22, 95% CI = 0.80 to 1.85) as found in analysis of first five trials. Trial sequential analysis indicated that the information size requirement was fulfilled to conclude the evidence for mechanical thrombectomy is robust. DISCUSSION: The impact of three recent trials on effectiveness and safety of mechanical thrombectomy was a more precise pooled effect size for functional independence. Trial sequential analysis demonstrated sufficient evidence for effectiveness and safety of mechanical thrombectomy. CONCLUSION: No further trials of mechanical thrombectomy versus no mechanical thrombectomy are indicated to establish clinical effectiveness. Uncertainty remains as to whether mechanical thrombectomy reduces mortality or increases risk of symptomatic intracranial haemorrhage.

9.
J Cereb Blood Flow Metab ; 36(2): 363-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26661175

RESUMO

The clinical relevance of the transient intraluminal filament model of middle cerebral artery occlusion (tMCAO) has been questioned due to distinct cerebral blood flow profiles upon reperfusion between tMCAO (abrupt reperfusion) and alteplase treatment (gradual reperfusion), resulting in differing pathophysiologies. Positive results from recent endovascular thrombectomy trials, where the occluding clot is mechanically removed, could revolutionize stroke treatment. The rapid cerebral blood flow restoration in both tMCAO and endovascular thrombectomy provides clinical relevance for this pre-clinical model. Any future clinical trials of neuroprotective agents as adjuncts to endovascular thrombectomy should consider tMCAO as the model of choice to determine pre-clinical efficacy.


Assuntos
Procedimentos Endovasculares/métodos , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/cirurgia , Trombectomia/métodos , Animais , Circulação Cerebrovascular , Modelos Animais de Doenças , Humanos
10.
Int J Stroke ; 10(8): 1168-78, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26310289

RESUMO

BACKGROUND: Acute ischemic strokes involving occlusion of large vessels usually recanalize poorly following treatment with intravenous thrombolysis. Recent studies have shown higher recanalization and higher good outcome rates with endovascular therapy compared with best medical management alone. A systematic review and meta-analysis investigating the benefits of all randomized controlled trials of endovascular thrombectomy where at least 25% of patients were treated with a thrombectomy device for the treatment of acute ischemic stroke compared with best medical treatment have yet to be performed. AIM: To perform a systematic review and a meta-analysis evaluating the effectiveness of endovascular thrombectomy compared with best medical care for treatment of acute ischemic stroke. SUMMARY OF REVIEW: Our search identified 437 publications, from which eight studies (totaling 2423 patients) matched the inclusion criteria. Overall, endovascular thrombectomy was associated with improved functional outcomes (modified Rankin Scale 0-2) [odds ratio 1·56 (1·32-1·85), P < 0·00001]. There was a tendency toward decreased mortality [odds ratio 0·84 (0·67-1·05), P = 0·12], and symptomatic intracerebral hemorrhage was not increased [odds ratio 1·03 (0·71-1·49), P = 0·88] compared with best medical management alone. The odds ratio for a favorable functional outcome increased to 2·23 (1·77-2·81, P < 0·00001) when newer generation thrombectomy devices were used in greater than 50% of the cases in each trial. CONCLUSIONS: There is clear evidence for improvement in functional independence with endovascular thrombectomy compared with standard medical care, suggesting that endovascular thrombectomy should be considered the standard effective treatment alongside thombolysis in eligible patients.


Assuntos
Isquemia Encefálica/cirurgia , Procedimentos Endovasculares , Acidente Vascular Cerebral/cirurgia , Trombectomia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
EuroIntervention ; 10(2): 271-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24531258

RESUMO

AIMS: The aim was to determine the incidence of new ischaemic lesions on diffusion-weighted MR imaging (DWI) in a non-randomised cohort of patients after protected and unprotected carotid artery stent placement using the Parodi Anti-Emboli System (PAES). METHODS AND RESULTS: A retrospective review was conducted on 269 patients who received DWI prior to, and 24-72 hours after, stent placement. All patients were enrolled in one centre. Forty patients stented with the PAES device were matched with 229 patients stented without protection (control group). New diffusion restriction on DWI was detected in 25.8% (PAES) versus 32.3% (control group); p=0.64. On average there were 0.7 lesions (PAES) versus 0.8 lesions (control group) per patient. The area of lesions was 1.7 (PAES) versus 5.6 mm2. In a subanalysis of patients (32 PAES, 148 non-protected) with >80% stenosis, the area of restricted diffusion was less when proximal protection was used (p<0.05). The number and area of DWI lesions did not differ on the contralateral, non-stented side. When the PAES system was used, patients were more likely not to have any lesion at all (p=0.028). CONCLUSIONS: In high-grade stenosis, the use of the Gore PAES device significantly reduced the area of new DWI lesions and patients were more likely not to have any new DWI lesion at all.


Assuntos
Angioplastia/instrumentação , Isquemia Encefálica/prevenção & controle , Estenose das Carótidas/terapia , Imagem de Difusão por Ressonância Magnética , Dispositivos de Proteção Embólica , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia/efeitos adversos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Desenho de Prótese , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
14.
J Invasive Cardiol ; 26(1): 30-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24402809

RESUMO

The purpose of this article is to give an overview of the management of the most common complications encountered during subarachnoid hemorrhage and endovascular treatment of intracranial aneurysms. We reviewed the literature and identified the complications encountered during endovascular treatment of intracranial aneurysms. We report current management strategies of complications associated with subarachnoid hemorrhage and the interventional procedure. Aneurysmal subarachnoid hemorrhage remains a devastating condition, with high mortality and poor outcome among survivors. The successful treatment of intracranial aneurysms requires a multidisciplinary approach and the treating physicians need to be aware of predisposing factors for complications, their frequency, and also their management.


Assuntos
Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Hemorragia Subaracnóidea/cirurgia , Humanos , Hidrocefalia/epidemiologia , Hidrocefalia/etiologia , Incidência , Convulsões/epidemiologia , Convulsões/etiologia , Hemorragia Subaracnóidea/mortalidade , Resultado do Tratamento , Vasoespasmo Intracraniano/epidemiologia , Vasoespasmo Intracraniano/etiologia
15.
Brain ; 136(Pt 12): 3528-53, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24038074

RESUMO

The science of metric-based patient stratification for intravenous thrombolysis, revolutionized by the landmark National Institute of Neurological Disorders and Stroke trial, has transformed acute ischaemic stroke therapy. Recanalization of an occluded artery produces tissue reperfusion that unequivocally improves outcome and function in patients with acute ischaemic stroke. Recanalization can be achieved mainly through intravenous thrombolysis, but other methods such as intra-arterial thrombolysis or mechanical thrombectomy can also be employed. Strict guidelines preclude many patients from being treated by intravenous thrombolysis due to the associated risks. The quiet art of informed patient selection by careful assessment of patient baseline factors and brain imaging could increase the number of eligible patients receiving intravenous thrombolysis. Outside of the existing eligibility criteria, patients may fall into therapeutic 'grey areas' and should be evaluated on a case by case basis. Important factors to consider include time of onset, age, and baseline blood glucose, blood pressure, stroke severity (as measured by National Institutes of Health Stroke Scale) and computer tomography changes (as measured by Alberta Stroke Programme Early Computed Tomography Score). Patients with traditional contraindications such as wake-up stroke, malignancy or dementia may have the potential to receive benefit from intravenous thrombolysis if they have favourable predictors of outcome from both clinical and imaging criteria. A proportion of patients experience complications or do not respond to intravenous thrombolysis. In these patients, other endovascular therapies or a combination of both may be used to provide benefit. Although an evidence-based approach to intravenous thrombolysis for acute ischaemic stroke is pivotal, it is imperative to examine those who might benefit outside of protocol-driven practice.


Assuntos
Seleção de Pacientes , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Terapia Trombolítica/métodos , Guias como Assunto , Humanos , Neuroimagem
16.
CNS Neurol Disord Drug Targets ; 12(2): 145-54, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23394531

RESUMO

Despite advances in the diagnosis and treatment of acute ischaemic stroke in the past two decades, stroke has remained the third cause of mortality and the single leading cause of disability worldwide. The immediate goal of acute ischaemic stroke therapy is to salvage the ischaemic penumbra through recanalisation of the occluded cerebral blood vessel. This is currently achieved through thrombolytics, which are pharmacological agents that can break up a clot blocking the flow of blood. To date, the only approved thrombolytic for treatment of acute ischaemic stroke is recombinant tissue plasminogen activator (alteplase, rt-PA), however, alteplase is substantially underused because of concerns regarding adverse bleeding risk. This limitation has fuelled the search for other thrombolytic agents, which display greater fibrin dependence and selectivity, but lack detrimental effects within the central nervous system. Development of alternative fibrinolytic agents that might be easier and safer to administer could lead to wider acceptance and use of thrombolytic therapy for stroke. Although other thrombolytic agents (e.g. streptokinase) have failed to show benefit over alteplase, there is still on-going research in search of alternative agents with higher target specificity and better safety profile. The potential thrombolytic agents with trials in progress include desmoteplase, tenecteplase, reteplase, plasmin and microplasmin. This review summarises current therapies with thrombolytics (e.g. alteplase and urokinase), their limitations and side effects, and also discusses ongoing clinical studies with the various potential emerging thrombolytic agents.


Assuntos
Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Animais , História do Século XX , História do Século XXI , Humanos , Terapia Trombolítica/história , Terapia Trombolítica/métodos , Terapia Trombolítica/tendências
17.
CNS Neurol Disord Drug Targets ; 12(2): 155-69, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23394532

RESUMO

Intravenous recombinant human tissue plasminogen activator (rtPA, formulated as alteplase) is the primary therapy for acute ischaemic stroke by breaking down a clot of an occluded vessel. There are several randomised controlled trials and observational studies that support the use of rtPA to improve functional outcome following acute ischaemic stroke. However, thrombolytic therapy with rtPA can be associated with a number of complications. Many of the rtPArelated complications result from its thrombolytic action including bleeding (intracerebral and systemic haemorrhage), reperfusion injury with oedema, and angioedema. Other rtPA complications such as reocclusion and secondary embolisation are related to ineffective thrombolysis or redistribution of the lysed clot. In addition to its thrombolytic properties, rtPA can act upon the brain parenchyma leading to seizures and neurotoxicity. Many of these complications have been reported in both pre-clinical experiments and in clinical trials. In animal studies, these complications of rtPA can confound the experimental results achieved, and have to be taken into account in future experiments. In the clinical setting, these complications are not always life-threatening, but can be serious and often lead to prolonged stays in intensive care units, increase the need for medical treatment, lengthen hospital stays, delay rehabilitation and increase morbidity and mortality. Some of these complications could be prevented through adherence to treatment guidelines or at least minimised through early detection and proper management. It is imperative that physicians caring for stroke patients have knowledge of these complications associated with rtPA treatment, and their management.


Assuntos
Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Animais , Humanos , Ativador de Plasminogênio Tecidual/biossíntese
18.
CNS Neurol Disord Drug Targets ; 12(2): 209-19, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23394533

RESUMO

No pharmacological intervention has been shown convincingly to improve neurological outcome in stroke patients after the brain tissue is infarcted. While conventional therapeutic strategies focus on preventing brain damage, stem cell treatment has the potential to repair the injured brain tissue. Stem cells not only produce a source of trophic molecules to minimize brain damage caused by ischaemia/reperfusion and promote recovery, but also potentially turn to new cells to replace those lost in ischaemic core. Although preclinical studies have shown promise, stem cell therapy for stroke treatment in human is still at an early stage and it is difficult to draw conclusions from current clinical trials about the efficacy of the different treatments used in humans. This article reviews the potential of various types of stem cells, from embryonic to adult to induced pluripotent stem cells, in stroke therapy, highlights new evidence from the ongoing clinical trials and discusses some of the problems associated with translating stem cell technology to a clinical therapy for stroke.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Avaliação Pré-Clínica de Medicamentos , Células-Tronco/fisiologia , Acidente Vascular Cerebral/terapia , Pesquisa Translacional Biomédica , Animais , Humanos , Isquemia/complicações , Acidente Vascular Cerebral/etiologia
19.
CNS Neurol Disord Drug Targets ; 12(2): 228-32, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23394534

RESUMO

BACKGROUND: Most studies evaluating long-term efficacy after coil embolisation of intracranial aneurysms have not differentiated between ruptured and unruptured aneurysms. OBJECTIVES: The aim of this study was to analyse factors that influence recanalisation in ruptured and unruptured aneurysms. METHODS: We performed a retrospective analysis of 182 (98 ruptured, 84 unruptured) aneurysms, treated with coil embolisation alone that received follow-up with digital substraction angiography (DSA). RESULTS: At 6 months 26% of the aneurysms showed recanalisation. Multivariate variance analysis revealed that different factors influenced recanalisation in ruptured and unruptured aneurysms. In ruptured aneurysms patient age was a determinant, with younger patients recanalising more frequently than older ones (p = 0.016). Also, low initial packing density led to higher recanalisation rates (p = 0.015) than higher packing. In the unruptured aneurysm group these factors were not significant. Here, only a larger aneurysm volume led to higher recanalisation rates (p = 0.027). CONCLUSIONS: Our data suggest that in ruptured aneurysms, high packing density is a key factor to prevent recanalisation, while in unruptured aneurysms, aneurysm volume is the main predictor for recanalisation.


Assuntos
Aneurisma Roto/cirurgia , Embolização Terapêutica/instrumentação , Embolização Terapêutica/métodos , Aneurisma Intracraniano/cirurgia , Angiografia Digital , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Instrumentos Cirúrgicos , Resultado do Tratamento
20.
CNS Neurol Disord Drug Targets ; 12(2): 233-41, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23394535

RESUMO

Cerebral vasospasm is a common and serious complication of aneurysmal subarachnoid haemorrhage. Despite the improvements in treatment of aneurysmal subarachnoid haemorrhage (aSAH), cerebral vasospasm complicating aSAH has remained the main cause of morbidity and mortality. Subarachnoid haemorrhage (SAH)-induced vasospasm is a complex entity caused by vasculopathy, impaired autoregulation, and hypovolaemia, causing a regional reduction of cerebral brain perfusion which can then induce ischaemia. Cerebral vasospasm can present either asymptomatically detected only radiologically or symptomatically (delayed ischaemic neurologic deficit). The various diagnostic approaches include the use of transcranial doppler, digital subtraction angiography and multimodal computed tomography (CT) and magnetic resonance (MR) techniques. Although digital subtraction angiography is usually the gold standard for the diagnosis of cerebral vasospam, transcranial doppler is commonly the first-screening method for the detection of cerebral vasospam. The treatment of subarachnoid haemorrhage -induced vasospasm include the use of both medical and endovascular therapy. The aim of this review is to discuss the various current therapeutic options and future perspective measures for reducing cerebral vasospasm induced stroke after SAH.


Assuntos
Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Vasoespasmo Intracraniano/diagnóstico , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/terapia
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