Joyce S. Balami

Complications of intracerebral haemorrhage

Intracerebral haemorrhage (ICH) is the most devastating type of stroke and is a leading cause of disability and mortality. By contrast with advances in ischaemic stroke treatment, few evidence-based targeted treatments exist for ICH. Management of ICH is largely supportive, with strategies aimed at the limitation of further brain injury and the prevention of associated complications, which add further detrimental effects to an already lethal disease and jeopardise clinical outcomes. Complications of ICH include haematoma expansion, perihaematomal oedema with increased intracranial pressure, intraventricular extension of haemorrhage with hydrocephalus, seizures, venous thrombotic events, hyperglycaemia, increased blood pressure, fever, and infections. In view of the restricted number of therapeutic options for patients with ICH, improved surveillance is needed for the prevention of these complications, or, when this is not possible, early detection and optimum management, which could be effective in the reduction of adverse effects early in the course of stroke and in the improvement of prognosis. Further studies are needed to enhance the evidence-based recommendations for the management of this important clinical problem.

Neuroprotection for ischaemic stroke: Translation from the bench to the bedside

Neuroprotection seeks to restrict injury to the brain parenchyma following an ischaemic insult by preventing salvageable neurons from dying. The concept of neuroprotection has shown promise in experimental studies, but has failed to translate into clinical success. Many reasons exist for this including the heterogeneity of human stroke and the lack of methodological agreement between preclinical and clinical studies. Even with the proposed Stroke Therapy Academic Industry Roundtable criteria for preclinical development of neuroprotective agents for stroke, we have still seen limited success in the clinic, an example being NXY-059, which fulfilled nearly all the Stroke Therapy Academic Industry Roundtable criteria. There are currently a number of ongoing trials for neuroprotective strategies including hypothermia and albumin, but the outcome of these approaches remains to be seen. Combination therapies with thrombolysis also need to be fully investigated, as restoration of oxygen and glucose will always be the best therapy to protect against cell death from stroke. There are also a number of promising neuroprotectants in preclinical development including haematopoietic growth factors, and inhibitors of the nicotinamide adenine dinucleotide phosphate oxidases, a source of free radical production which is a key step in the pathophysiology of acute ischaemic stroke. For these neuroprotectants to succeed, essential quality standards need to be adhered to; however, these must remain realistic as the evidence that standardization of procedures improves translational success remains absent for stroke.

Ischemic stroke in the elderly: an overview of evidence

Stroke mostly occurs in elderly people and patient outcomes after stroke are highly influenced by age. A better understanding of the causes of stroke in the elderly might have important practical implications not only for clinical management, but also for preventive strategies and future health-care policies. In this Review, we explore the evidence from both human and animal studies relating to the effect of old age—in terms of susceptibility, patient outcomes and response to treatment—on ischemic stroke. Several aging-related changes in the brain have been identified that are associated with an increase in vulnerability to ischemic stroke in the elderly. Furthermore, risk factor profiles for stroke and mechanisms of ischemic injury differ between young and elderly patients. Elderly patients with ischemic stroke often receive less-effective treatment and have poorer outcomes than younger individuals who develop this condition. Neuroprotective agents for ischemic stroke have been sought for decades but none has proved effective in humans. One contributing factor for this translational failure is that most preclinical studies have used young animals. Future research on ischemic stroke should consider age as a factor that influences stroke prevention and treatment, and should focus on the management of acute stroke in the elderly to reduce the incidence and improve outcomes in this vulnerable group.

Neurological complications of acute ischaemic stroke

Complications after ischaemic stroke, including both neurological and medical complications, are a major cause of morbidity and mortality. Neurological complications, such as brain oedema or haemorrhagic transformation, occur earlier than do medical complications and can affect outcomes with potential serious short-term and long-term consequences. Some of these complications could be prevented or, when this is not possible, early detection and proper management could be effective in reducing the adverse effects. However, there is little evidence-based data to guide the management of these neurological complications. There is a clear need for improved surveillance and specific interventions for the prevention, early diagnosis, and proper management of neurological complications during the acute phase of stroke to reduce stroke morbidity and mortality.

A systematic review and meta-analysis of randomized controlled trials of endovascular thrombectomy compared with best medical treatment for acute ischemic stroke.

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.

Complications Associated with Recombinant Tissue Plasminogen Activator Therapy for Acute Ischaemic Stroke

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.

Endovascular Stroke Treatment Today

SUMMARY: The purpose of this study was to review current treatment options in acute ischemic stroke, focusing on the latest advances in the field of mechanical recanalization. These devices recently made available for endovascular intracranial thrombectomy show great potential in acute stroke treatments. Compelling evidence of their recanalization efficacy comes from current mechanical embolectomy trials. In addition to allowing an extension of the therapeutic time window, mechanical recanalization devices can be used without adjuvant thrombolytic therapy, thus diminishing the intracranial bleeding risk. Therefore, these devices are particularly suitable in patients in whom thrombolytic therapy is contraindicated. IV and IA thrombolysis and bridging therapy are viable options in acute stroke treatment. Mechanical recanalization devices can potentially have a clinically relevant impact in the interventional treatment of stroke, but at the present time, a randomized study would be beneficial.

Thrombolytic Agents for Acute Ischaemic Stroke Treatment: The Past, Present and Future

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.

The transient intraluminal filament middle cerebral artery occlusion model as a model of endovascular thrombectomy in stroke

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.

Different factors influence recanalisation rate after coiling in ruptured and unruptured intracranial aneurysms.

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.