Frontiers in Neurosurgery

Stroke is a pathology that has a heavy socio-economic impact, considering that the annual incidence is 15 million new cases and only one-third of these has a positive clinical outcome. Stroke is the cause of 4% of all disabilities and it does, therefore, have very high indirect social costs. The purpose of this chapter is to analyse the societal costs of stroke and compare the various treatments in order to determine which gives the best results for a contained cost.

Clinical outcome was analysed using the modified Rankin Scale (mRS), in which patients are allocated a score that depends on the presence of neurological symptoms and an impaired capacity to perform daily-life activities. The indirect costs related to reduced productivity were calculated through the analysis of various indices: disabilityadjusted life years (DAYLs), years of life lost (YLL) and years lived with disability (YLD).

We calculated that a mRS score <2 obtained in 13.5% more of cases by using endovascular treatment in patients with occlusion of large vessels rather than venous fibrinolysis would lead to a saving of about 56 billion euros. Using data on the lifetime cost of a stroke, we calculated that a saving of about 11,400 billion euros could be achieved with endovascular treatment.

Clearly the savings are related to positive results that avoid indirect costs, in an ideal situation in which all patients are treated with endovascular methods. In any case, the analysis is a mathematical demonstration of the notable potential of this therapeutic technique.

Brain function and viability strictly depend on blood flow. In case of arrest of the cerebral circulation the brain cells would survive for only a few minutes. In the perinecrotic area, where a residual blood flow is present, the brain tissue may survive for a few hours or probably days to eventually die or regain function. Both innate and adaptive immune responses, together with oxidative stress and excitotoxicity activate a damage maturation process. The interplay of the events within the neurovascular unit includes both deleterious and protective mechanisms. The complexity of the postischemic damage offers a number of potential therapeutic opportunities. The same complexity, however, makes it likely that each individual, potentially therapeutic, approach embraces antithetical effects, by affecting both the deleterious and protective mechanisms that drive the maturation process. The perinecrotic area seems therefore to express a heterogeneous scenario, where a patchy pattern reflects different pathologic states, depending on the intensity of the ischemic insult and on both local and systemic variables.

Stroke represents an important cause of death and permanent disability in the industrialized world. Diagnostic imaging plays a key role in the clinical process, distinguishing, early in the acute phase, ischaemic stroke from primary haemorrhagic stroke. Nowadays, new imaging techniques, such as Computed Tomography Angiography (CTA), Magnetic Resonance Angiography (MRA) and perfusion imaging represents important tools in the definition of the severity of ischaemic stroke. The aim of advanced imaging techniques is to identify cerebral ischaemia within the first few hours and distinguish normal cerebral tissue from that at risk. This chapter focuses on imaging characteristics of stroke, with their anatomic-radiologic correlations, emphasizing the role of new imaging techniques, with their strengths and weaknesses.

Despite the stroke burden has globally increased, particularly due to high rates of mortality and dependency in developing countries [1], advances are being made. In the last two decades, we witnessed important successes in the management of acute stroke patients, the principal of them being the development of stroke units, aspirin for the early secondary prevention, thrombolysis for the reperfusion of ischemic areas and decompressive craniectomy for malignant strokes.

This chapter will focus on the medical management of acute stroke, in particular on the thrombolytic treatment.

Acute ischemic stroke (AIS) is a significant medical disease with relevant mortality and morbidity associated, that, especially in recent years, has undergone a major development of drugs and devices used for its treatment. A poor number of patients respects the criteria for treatment with intravenous drug (IVT) with recombinant tissue plasminogen activator, and the efficacy of this treatment in large vessel occlusion is percentually low. Recently, incresead percentage number of patients with AIS are treated with mechanical embolectomy if IVT is ineffective or controindicated. An important technological upgrading of devices used for the endovascular treatment of AIS, has allowed a significant increase in rates of recanalization and neurological improvement of patients treated, completely replacing the old device. Furthermore the use of these new devices has not caused an increase in intracerebral hemorragic (ICH). This chapter highlights the devices used in current practice for endovascular treatment of AIS, the different endovascular approaches and a brief review about the recent randomized trials, which have evaluated the efficacy of these new devices.

Acute ischemic stroke secondary to large vessel occlusion (LVO) is a devastating condition resulting in death and disability in a high proportion of patients. Over the last 2 decades, we have witnessed a tremendous progress in the treatment of this disease. In fact, from an observational and mostly supportive care we are now in the era of acute endovascular intervention.

The first step in the right direction was the NIH/NINDS intravenous (IV) tissue plasminogen activator (tPA) trial. The trial introduced the concept of time-sensitive intervention in acute ischemic stroke. Subsequently, the endovascular approach was pioneered as treatment for this condition. However, 3 clinical randomized trials SYNTHESIS Expansion, IMS III and MR RESCUE failed to demonstrate superiority of the endovascular approach over standard IV tPA therapy. There were several drawbacks in these trials including i) not always demonstration of a LVO ii) long time to intervention and iii) most importantly, use of first generation thrombectomy devices. In fact, while these trials were ongoing, retrievable stents in SWIFT and TREVO 1 and 2 showed to be superior to first generation thrombectomy devices.

Using latest generation technology, MR CLEAN, ESCAPE, EXTEND IA, SWIFTPRIME and REVASCAT, 5 multicenter, controlled, randomized, clinical trials showed overwhelming superiority of the endovascular approach over medical management for acute LVO.

Ischemic strokes caused by the complete occlusion of an intracranial artery are associated with poor outcomes overall, and high mortality rates. To improve the survival and the outcome otherwise not afforded by the available medical and interventional therapies a neurosurgical approach must be considered. In selected patients a microsurgical embolectomy and a decompressive craniectomy are effective therapies with which to treat occlusions of the middle cerebral artery or other territories when thrombolysis or an interventional endovascular embolectomy does not restore the vascular flow. A bypass procedure that employs a superficial temporal artery-to-middle cerebral artery (STA-to-MCA) surgical anastomosis can be performed to improve the blood flow in a deficient artery chronic angiopathic disorder.

Cerebral venous thrombosis is a quite infrequent condition (3-4 per million) that affects predominantely young patients. It is typically characterized by a variable clinical spectrum and prognosis is influenced by several factors. Diagnosis is sometimes difficult since symptomatology is often non-specific. Imaging work-up by CT and MRI plays an important role in patient triage and diagnosis. Modern modalities allow an excellent visualizaion of the venous system and a precise identification of the intra-luminal thrombus. Imaging may also add an interesting prognostic value. Medical management mainly consists in anticoagulation, reduction of intracranial hypertension and treatment of underlying triggering conditions. In recent years, endovascular techniques have emerged as a new interesting option in patients poorly responding to medical therapy, with promising results. In this chapter, we sought to review the current knowledge on the clinical management, imaging diagnosis, medical and endovascular treatment of this pathology.

Intra-Cranial Arterial Stenosis (ICAS) represents a source of risk to develop stroke. There is some genetic and ethnic determinant in having a major risk. Non invasive diagnosis rely on Trans-Cranial Doppler (TCD) and Magnetic Resonance Angiography, while Computed Tomography has the best accuracy to be compared to the more invasive Digital Subtraction Angiography. The endovascular and medical therapy options are compared, passing through WASID and SAMMPRIS trials.

This chapter contains detailed, up-to-date information about the nature, diagnosis, and treatment of those relatively uncommon types of cerebrovascular disease that cause strokes. Although many of the conditions discussed are rare, the chapter covers the causes of up to 10% to 15% of all strokes and of up to 40% of strokes in young adults. This chapter may be an essential resource to help physicians diagnose and treat stroke patients who do not fit well into the usual clinical categories.

Discussed within are the dissection of carotid and vertebral arteries, the more relevant cause of stroke in the young. The collagen vascular disorders causing stroke as a consequence of dissection , occlusion and, more rarely, rupture of extracranial and intracranial arteries are reported in detail. Various forms of cerebral angiitis, with focus on the primary central system vasculitis and reversible cerebral vasoconstriction syndrome are discussed.

This chapter contains detailed, up-to-date information about the nature, diagnosis, and treatment of those relatively uncommon types of cerebrovascular disease that cause strokes. Although many of the conditions discussed are rare, the chapter covers the causes of up to 10% to 15% of all strokes and of up to 40% of strokes in young adults. This chapter may be an essential resource to help physicians diagnose and treat stroke patients who do not fit well into the usual clinical categories.

Discussed in this chapter are the various form of inherited small vessel disease such as CADASIL but even the less known Col 4A1/2 related syndromes, CARASIL, TREX1- gene mutations disorders and the cerebroretinal microangiopathy with calcifications and cysts. Three form of metabolic disorders causing stroke such as Fabry disease, Homocystinuria and MELAS as well as the most relevant form of hematological disorders (antifospholipid syndrome and sickle cell disease) are discussed. Finally intriguing disorders such as migrainous infarction and drugs related stroke disorders are detailed as well as some other rare disease such as Kohlmeier–Degos disease and acute posterior multifocal placoid pigment epiteliopathy.

Treatment of lesions of the extracranial internal carotid artery plays an important role in the management of ischemic stroke, particularly in the secondary prevention of further events, but sometimes also in the acute phase. The endovascular management of atherosclerotic stenosis is not just an alternative to endarterectomy but frequently is the treatment of choice. Moreover, treatment of dissections of the carotid arteries, when not exclusively medical, is in almost all cases endovascular. Experience in the neurointerventional field is necessary to correctly deal with both types of lesions of the extracranial internal carotid artery.

Acute ischemic stroke represents a leading cause of mortality and morbidity worldwide. An increasing number of patients with massive stroke require admission to ICU for neurological monitoring and management of acute complications. Medical treatment in ICU consists of sedation, analgesia, ventilator support, hemodynamic monitoring, neuromonitoring, fluid management, thromboprophylaxis and treatment of complications. Principal complications are: cerebral edema, hemorrhage, seizures, myocardial complications, hyperglycemia and fever. Severe cerebral edema after stroke represents an important complication. In this case, decompressive craniectomy successfully decreases mortality and morbidity in patients with severe cerebral edema. Therapy with mannitol is the standard treatment for intracranial hypertension. Therapeutic hypothermia may also be considered for its neuroprotective effect but its role is not demonstrated in stroke. These aspects of critical care are considered in this chapter.

In this chapter, we focus on the recently published randomized controlled trials examining combined endovascular therapy with IV tPA versus IV tPA alone. In October 2014, the first evidence was presented from a randomized clinical trial conducted in the Netherlands showing the benefit of endovascular therapy in acute ischemic stroke secondary to emergent large vessel occlusion in the anterior circulation. Four randomized controlled trials later confirmed these results. The advances in techniques and devices which enabled these positive findings for intraarterial therapy, including aspiration thrombectomy, stent retrievers, and combination strategies will be discussed herein. We will also consider where opportunities remain to maximize favorable outcomes while minimizing costs as these recent trial results are translated into clinical practice.

Acute ischemic stroke is a major cause of mortality and morbidity and its treatment has attracted great interest in the last decades. Innovative instruments such as stent-retrievers, intermediate catheters, and large-bore catheters have recently been introduced to perform endovascular thrombectomy. In cases of large vessel occlusion, this technique produces better results than intravenous pharmacological treatment.

In this chapter, we discuss the history of devices developed for thrombectomy, concluding with the state-of-the-art devices in each category.