1. Introduction
1.1. Stroke Definitions
According to the World Health Organization, a stroke is defined as ‘a clinical syndrome consisting of rapidly developing clinical signs of focal (or global in case of coma) disturbance of cerebral function lasting more than 24 h or leading to death with no apparent cause other than a vascular origin’. On the other hand, a transient ischemic attack (TIA) presents the signs and symptoms of a stroke, but without tissue damage and the symptoms usually resolve within 24 h [1,2]. A stroke can be defined as a rupture or blockage of an artery of the brain, which results in bleeding into the brain parenchyma or in decreased blood supply and ischemic damage to specific brain areas respectively [3]. 1.2. Epidemiology of Illicit Drugs of Abuse Use and Stroke
The use of psychoactive substances has been known for thousands of years: From the ingestion of plant derivatives, such as the mushroom Psilocybe hispanica used in religious rituals performed 6000 years ago, to the abuse of synthetic drugs, such as heroin that was first synthesized in 1874 by C. R. Alder Wright, an English chemist working at St. Mary’s Hospital Medical School in London. Nowadays, substance abuse constitutes a major social and medical problem. According to the World Drug Report 2017, issued by the United Nations Office on Drugs and Crime, the number of estimated drug users worldwide has increased by 23% in 11 years, reaching 255 million individuals in 2015. At the same time, drug users with various health disorders, such as lung or heart disease, mental health diseases, infectious diseases, stroke and cancer, reached 29.5 million in 2015, with an increase of 13.5% compared to 2006. The number of deaths attributed to drug abuse has also significantly increased. Out of the total registered deaths due to drug abuse, 67.5% are attributed to amphetamine use, 49.7% to cocaine, 29.6% to opioids and the remaining 23% to other drugs [4].Stroke is the second leading cause of death in the world, responsible for 5.7 million deaths every year, which is expected to reach approximately 7.8 million by 2030 [5,6,7,8]. Moreover, stroke is the leading cause of major disability. A timely diagnosis by computed tomography (CT) and, depending on the circumstances, by CT angiography and CT perfusion is necessary to assure effective management [3,7].Read more A Beginner’s Guide to Japanese Stroke Order
1.3. Classic Concept of Stroke Pathophysiology
A stroke occurs when blood circulation of the brain is disturbed. There are two types of strokes: Ischemic stroke/transient ischemic attack (TIA) and hemorrhagic stroke. Brain tissue destruction is caused by different mechanisms with multifactorial character in the two types of strokes.Ischemic stroke represents the loss of brain function caused by a decreased blood flow and consequently reduced oxygen supply to the affected brain tissue [9].The knowledge of the latest physiopathological mechanisms in ischemic stroke is important for the development of new pharmacotherapies. Recent experimental studies in mice with transient middle cerebral artery occlusion (tMCAO) have shown the involvement of the Von Willebrandt factor (vWF) which interacts with and binds to the GPI platelet glycoprotein and the collagen receptor GP VI [10]. This vWF–GPIb axis combined with activated coagulation factor XII triggers the thrombo-inflammatory cascade in acute ischemic stroke [10,11]. In this thrombo-inflammatory process, platelets interact with T cells, which aggravate ischemia-reperfusion injury after recanalization [10,11]. However, targeting stroke-related neuroinflammation with anti-inflammatory drugs may be used with caution in order to detect any potential adverse effects to be avoided [11].Numerous other pathophysiological studies performed on patients with ischemic stroke demonstrated hemostatic abnormalities such as low serum levels of coagulation factor VII, FVII-activated antithrombin complex, tissue factor and increased serum levels of tissue factor-bearing microparticles (MPs-TF) [12,13].In hemorrhagic stroke the neuronal injury is supplemented by the compressive effect exerted by the hematoma, the systemic inflammatory response, the neuronal toxicity of the hemoglobin and the effect thrombolysis inside the intracerebral thrombus [14,15].A key role in controlling stroke mortality lies in controlling the so-called modifiable stroke risk factors [3]. There are several risk factors for stroke including age, gender, hypertension, diabetes mellitus, dyslipidemia, atheromatosis, thrombophilia, atrial fibrillation, sick sinus syndrome, patent foramen ovale or family history of cardiovascular events, hyperhomocysteinemia as well as lifestyle habits, such as low physical activity, obesity, tobacco smoking, poor diet, and alcohol consumption [3,5,6,8,16,17,18]. Controlling blood pressure and blood glucose levels, using statins for elevated blood lipid levels and reducing the use of oral contraceptives, along with lifestyle changes, can drastically reduce the risk for stroke [5].Drugs of abuse are also associated with stroke, especially in younger individuals. It has been shown that drug users, between 15 and 44 years old, were 6.5 times more likely to have a stroke compared with non-users [19]. The major classes of drugs linked to stroke are cocaine, amphetamines, heroin, morphine, cannabis, and the new synthetic cannabinoids, along with androgenic anabolic steroids, which are widely used both by professional and recreational athletes but also by the general public.This article aims to review epidemiological evidence related to drug abuse-associated stroke and elucidate the possible underlying mechanisms of stroke induced by different classes of drugs of abuse.
