For the section on intra-arterial thrombectomy with mechanical devices, we searched PubMed between 1965 and March, 2013, with the terms (and synonyms) “acute stroke”, “cerebral ischaemia”, “cerebral infarction”, “interventional”, “mechanical”, “thrombectomy”, and “device”. Abstracts of retrieved citations were reviewed and prioritised by relevant content, particularly the quality of evidence reported. We selected mainly studies with a prospective design or those that reported findings in at
ReviewNon-pharmacological strategies for the treatment of acute ischaemic stroke
Introduction
In the USA and Europe, stroke has dropped from being the third leading cause of death to the fourth.1 However, stroke remains the leading cause of physical disability and can also lead to post-stroke dementia, depression, personality changes, and sometimes pain. While improved management of risk factors for, and cardiovascular causes of, ischaemic stroke has contributed to a decline in the frequency of both primary and recurrent stroke, intravenous fibrinolysis with alteplase remains the only approved medical treatment specific for patients with acute ischaemic stroke presenting within 4·5 h after symptom onset.2, 3
In 1995, findings of a National Institute of Neurological Disorders and Stroke (NINDS) trial showed a benefit of intravenous thrombolytic treatment if started within 180 min after the onset of symptoms.2 A pooled analysis of data from alteplase trials showed that early treatment led to better outcomes, although benefit was seen up to 4·5 h after onset.4 This finding was confirmed by the ECASS III trial, which showed that intravenous alteplase administered 3–4·5 h after the onset of symptoms significantly improved clinical outcomes in patients with acute ischaemic stroke, compared with placebo.3 Results of the observational SITS-MOST study verified that alteplase is safe in a clinical setting when given 3–4·5 h after the onset of symptoms in patients with acute ischaemic stroke,5, 6 and in November, 2011, the European Medicines Agency (EMEA) approved the use of alteplase within 4·5 h after symptom onset (the US Food and Drug Administration have only approved alteplase for use within 3 h).
However, the heterogeneity of individual responses to intravenous alteplase has led to the use of additional intra-arterial thrombolytic and mechanical endovascular treatments for acute ischaemic stroke. Optimisation of early recanalisation rates, augmentation of collateral blood supply, and, in turn, improvement of clinical outcomes are the challenging goals of non-pharmacological strategies for the treatment of acute ischaemic stroke and the subject of many ongoing studies.
In this Review, we describe current ideas and knowledge about the mode of action of non-pharmacological stroke treatment strategies that aim at recanalisation, reperfusion, neuroprotection, and collateral flow augmentation. Furthermore, we present safety and efficacy data from clinical trials of these non-pharmacological strategies. We discuss surgical procedures that aim to improve survival and outcome in malignant infarction. Finally, we highlight how standard intravenous thrombolysis might be complemented by additional or alternative treatment options.
Section snippets
Pharmacological treatment and the bridging concept
As the only evidence-based and approved treatment strategy for acute ischaemic stroke, administration of intravenous alteplase to patients in whom symptoms started no more than 3 h or 4·5 h earlier is, in general, advised by US and European guidelines, respectively, for stroke management.7, 8 Additional or alternative treatment options are selected on the basis of national or international recommendations and institutional standards. In most centres that offer intravenous thrombolysis for
Intra-arterial thrombectomy with mechanical devices
Table 1 presents data from prospective studies of thrombectomy devices.26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 The first neurovascular system designed for embolectomy—the Merci retriever (Concentric Medical, Hertogenbosch, Netherlands)—was approved by the US Food and Drug Administration (FDA) in August, 2004, for the restoration of blood flow by removal of a thrombus from the neurovasculature. In the prospective, non-randomised MERCI trial,26 the device was used in 141 patients
Ultrasound-enhanced thrombolysis
The idea of using ultrasound to amplify thrombolytic treatment is based on the finding, first described in the 1970s,48 that recanalisation is facilitated by ultrasonic mechanical pressure waves. Microstreaming—the motion of fluid around a thrombus—is another noted effect of ultrasound, possibly enhancing contact with alteplase. However, only a few trials of ultrasound-enhanced thrombolysis have been reported (table 3).11, 12, 49, 50, 51, 52, 53
CLOTBUST was a randomised, open-label, multicentre
Decompressive surgery for malignant stroke
Removal of the cranium to allow space for brain tissue to expand after infarction is a surgical option used for patients who have large supratentorial infarcts that otherwise could lead to death by brainstem herniation (figure 2). Even though decompressive surgery is done in many stroke centres worldwide, the ideal candidates for the procedure, the best time to undertake the treatment, and the technique of the surgery itself are still a matter of debate. Data from three small controlled trials
Conclusions
Here, we have reported several strategies for the treatment of acute ischaemic stroke beyond pharmacological interventions. The need for new therapeutic options is attributable to the inherent limitations of intravenous alteplase, which remains the only evidence-based treatment for patients with acute ischaemic stroke within 4·5 h after the onset of symptoms. Many acute stroke patients do not receive this treatment because of the limited time-window or different approval restrictions;
Search strategy and selection criteria
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Cited by (33)
Ageing as a risk factor for cerebral ischemia: Underlying mechanisms and therapy in animal models and in the clinic
2020, Mechanisms of Ageing and DevelopmentCitation Excerpt :Higher body temperatures before or after endovascular thrombectomy were associated with poorer clinical outcomes (Diprose et al., 2020). Therefore, to minimize the incapacitating sequelae of stroke during the acute and post-acute phase of stroke, a promising focus of research is physical cooling, or hypothermia, either confined to the head or including the entire body (Esposito et al., 2014; Hennerici et al., 2013; Kollmar et al., 2007; Wu and Grotta, 2013; Kurisu and Yenari, 2017). The feasibility of hypothermia to reduce sequelae after stroke and improve functional recovery has been addressed by several studies in stroke patients.
Acute Stroke Management
2018, Neurocritical Care Management of the Neurosurgical PatientTwenty-four hours hypothermia has temporary efficacy in reducing brain infarction and inflammation in aged rats
2016, Neurobiology of AgingCitation Excerpt :To minimize the incapacitating sequelae of stroke, a promising focus of research is on long-term neuroprotective strategies that minimize functional impairment by preventing the death of neurons, which continues for days to weeks after focal cerebral ischemia. A viable alternative to conventional drug-based therapies is physical cooling, or hypothermia, either confined to the head or including the entire body (Esposito et al., 2014; Hennerici et al., 2013; Kollmar et al., 2007; Wu and Grotta, 2013). The feasibility of hypothermia (either by surface or endovascular cooling) has been addressed by several studies both in traumatic brain injury (for a review, see Dietrich and Bramlett, 2010) and stroke patients.
Therapeutic hypothermia applicable to cardiac surgery
2015, Veterinary Anaesthesia and AnalgesiaCitation Excerpt :Deep hypothermic circulatory arrest (DHCA) has also been recommended for surgical procedures which carry a high risk for profound intraoperative haemorrhage, such as renal tumours with caval invasion (Conolly et al. 2010). Moreover, TH has become an integral part of treatment regimens for traumatic brain injury (TBI) (Mrozek et al. 2012; Adelson et al. 2013) and spinal cord injury (SCI) (Kwon et al. 2008; Batchelor et al. 2013; Ahmad et al. 2014), and in comatose human patients after successful cardiopulmonary resuscitation after out-of-hospital cardiac arrest (Kabon et al. 2003; Kelly & Nolan 2010; Diao et al. 2013) and for acute stroke (Berger et al. 2004; Lyden et al. 2006; Hennerici et al. 2013). Furthermore, systemic reviews have indicated that TH may reduce the risk for mortality and neurodevelopmental disability in paediatric patients suffering from neonatal hypoxic-ischaemic encephalopathy (HIE) attributable to acute perinatal asphyxia or TBI (Shankaran et al. 2005; Shah 2010; Adelson et al. 2013).