Acute Brain Impairment: Scientific Discoveries and Translational Research
348
Acute Brain Impairment: Scientific Discoveries and Translational Research
348eBook
Available on Compatible NOOK devices, the free NOOK App and in My Digital Library.
Related collections and offers
Overview
A rise in the number of young and old patients suffering from a stroke or traumatic brain injury has led to the need for better drug development and treatment, as well as diagnosis and prevention of ischemic stroke and traumatic brain injury. This book provides a comprehensive overview of scientific advancements in these areas.
Chapters provide the latest knowledge in neuroscience, biotechnology, and personalized medicine applicable to acute brain injuries. Development of neuroprotective drugs is treated in detail. Chemical biomarkers for detection, imaging and preventative strategies are covered to provide medicinal chemists with a broad view of translational aspects of the field.
This book will be useful to postgraduate students and researchers in medicinal chemistry and pharmacology as well as specialists in the acute brain injury field.
Product Details
| ISBN-13: | 9781788013376 |
|---|---|
| Publisher: | Royal Society of Chemistry |
| Publication date: | 11/17/2017 |
| Series: | ISSN |
| Sold by: | Barnes & Noble |
| Format: | eBook |
| Pages: | 348 |
| File size: | 4 MB |
Read an Excerpt
CHAPTER 1
Transient Ischemic Attack, Traumatic Brain Injury, and Ischemic Stroke: Risk Factors and Treatments
PHILIP V. PEPLOW AND JACQUELINE J. T. LIAW
1.1 Introduction
The overall burden of stroke in the number of people affected is increasing, especially in the younger age groups and in lower-to-middle-income countries. Despite some improvements in stroke prevention and management in high-income countries, the growth and aging of the global population is leading to a rise in the number of young and old patients with stroke. Closely related to this is the increasing number of people, including young children, who are overweight or obese. Obesity is a risk factor for stroke on account of it leading to atherosclerosis, which promotes thrombosis and obstruction to the flow of blood. Moreover, there is an increasing prevalence of hypertension, which also leads to atherosclerosis, and this in turn can lead to blockage of small blood vessels in the brain, causing stroke.
In people experiencing a transient ischemic attack (TIA), the incidence of subsequent stroke is as high as 11% over the next 7 days and 24–29% over the following 5 years. Unlike a stroke, the symptoms of a TIA can resolve within a few minutes or within 24 hours. However, brain injury may still occur in a TIA lasting only a few minutes. A strong association has been shown between traumatic brain injury (TBI) and later development of ischemic stroke, which remained significant even after several potential confounders, such as vascular risk factors and comorbidities, were taken into consideration. The association was similar in magnitude to that of hypertension, which is the leading stroke risk factor.
1.2 Definition of TIA, TBI, and Stroke
Early definitions of stroke and TIA focused on the duration of symptoms and signs. More recently, using clinical observation and modern brain imaging, it has been shown that the duration and reversibility of brain ischemia are variable. While brain tissue deprived of needed nutrients undergoes irreversible damage (infarction) in most individuals, in some patients it can survive for a considerable period of time, which may be several hours or even, rarely, days. In 2009, an expert committee of the American Heart Association/American Stroke Association (AHA/ASA) published a scientific statement defining TIA as a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia without acute infarction. The word 'transient' indicates a lack of permanence. However, modern brain imaging has shown that many patients in whom symptoms and signs of brain ischemia are clinically transient have evidence of brain infarction. Similarly, ischemia may produce symptoms and signs that are prolonged (and would qualify as strokes in older definitions) and yet no permanent brain infarction has occurred. In 2013, the AHA/ASA published a scientific statement defining ischemic stroke as an episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction. Stroke caused by intracerebral hemorrhage was defined as rapidly developing clinical signs of neurological dysfunction attributable to a focal collection of blood within the brain parenchyma or ventricular system that is not caused by trauma. Likewise, stroke caused by subarachnoid hemorrhage was defined as rapidly developing clinical signs of neurological dysfunction and/or headache because of bleeding into the subarachnoid space between the arachnoid membrane and the pia mater of the brain or spinal cord, which is not caused by trauma. TBI has been defined as a non-degenerative, non-congenital insult to the brain from an external mechanical force, possibly leading to permanent or temporary impairment of cognitive, physical, and psychosocial functions, with an associated diminished or altered state of consciousness. It usually results from a violent blow or jolt to the head or body. The resulting brain damage can be focal or diffuse. A focal TBI is usually caused by sudden contact; diffuse injury is more likely to be caused by an acceleration/ deceleration trauma. The severity of TBI is determined by the nature, speed, and location of the impact, and by complications such as hypotension, intracranial hemorrhage, or increased intracranial pressure. These complications may cause secondary injury hours or even days after the trauma.
1.3 Incidence of TIA, TBI, and Stroke
Precise estimates of the incidence and prevalence of TIAs are difficult to determine because of varying criteria used in epidemiological studies to identify TIA. Failure of recognition by both the public and health professionals of the transitory focal neurological symptoms associated with TIAs may also lead to significant underestimates. Given these limitations, the incidence of TIA in the United States has been estimated to be 200 000–500 000 per year, with a population prevalence of 2.3%, which equated to 5 million individuals in 1999. TIA incidence markedly increases with age and varies by race–ethnicity. The prevalence rate varies depending on the age distribution of the study population. The Cardiovascular Health Study estimated a prevalence of TIA in men of 2.7% for 65–69 years of age and 3.6% for 75–79 years of age. For women, TIA prevalence was 1.6% for 65–69 years of age and 4.1% for 75–79 years of age. In the Atherosclerosis Risk in Communities Study, the overall prevalence of TIAs among adults 45–64 years of age was 0.4%. Among patients who present with stroke, the prevalence of prior TIA may range from 7% to 40% depending on how TIA is defined, which stroke subtypes are evaluated, and whether the study is a population-based series or a hospital-based series. Variability in the use of brain imaging and the type of diagnostic imaging used can also affect estimates of the incidence and prevalence of TIAs. For example, a revision of the TIA definition to include the absence of changes on magnetic resonance imaging could lead to a decrease in the incidence of TIAs by 33% and a resultant 7% increase in the number of cases labeled as stroke.
Approximately 795 000 strokes occur each year in the United States. In total, 10–20% of patients have a stroke within 90 days following a TIA, and in up to 50% of these patients the stroke occurs within 24–48 hours. In 2000, there were 167 661 deaths in the United States attributable to stroke, which was nearly 24% of stroke patients. The AHA/ASA reported that among non-Hispanic blacks, the relative risk of stroke is four-times higher than among whites at 35–54 years of age and three-times higher at 55–64 years of age. Among Hispanics and American Indians/Alaska natives, the relative risk is about 1.3-times higher than in whites at 35–64 and 45–54 years of age, respectively. Ischemic stroke accounts for 87% of all strokes and can be divided into two main types: thrombotic and embolic. Thrombotic disease accounts for about 60% of acute ischemic strokes. It is estimated that 14–30% of ischemic strokes are cardioembolic in origin. The incidence of cardioembolic strokes increases with age.
TBI is the greatest cause of mortality and disability in young adults in modern Western societies. In the United States, 1.6 million people sustain a TBI each year, approximately 50 000 people die from a TBI, and 125 000 people are disabled 1 year after injury. However, the exact facts and figures on the incidence, prevalence, and long-term consequences of TBI are uncertain, and it is likely the incidence figures have to be multiplied by 5 or even 10 in order to include every unregistered patient. TBI is strongly associated with several neurological disorders 6 months or more after injury. Seizures are associated with most types of TBI. About 25% of patients with brain contusions or hematomas and about 50% of patients with penetrating head injuries will develop seizures within the first 24 hours of the injury.
1.4 Risk Factors for TIA and Stroke
1.4.1 Age
The most important of the non-modifiable risk factors associated with stroke is age. Stroke is most prevalent among the elderly and the majority of strokes occur in those aged >65 years. Age-related risk also increases for TIA, except for those in the oldest category (Z85 years), where it may decrease slightly.
1.4.2 Gender
Men are at greater risk of stroke, with the incidence rate being 1.25-times higher than in women. Some differences between the genders have also been noted for stroke subtype. Men have about a fourfold greater age-adjusted incidence rate of ischemic stroke due to large vessel atherosclerosis than women, which may account for their higher rate of undergoing carotid endarterectomy.
1.4.3 Race
Significant differences in stroke frequency have been found for race. Black Americans have a higher incidence of stroke than whites. The age- and gender-adjusted ischemic stroke incidence for blacks is 246 per 100 000, compared with 147 per 100 000 for whites. Racial differences have also been found for the distribution of stroke subtype. Stroke due to large vessel atherosclerosis occurs more often among whites (27 per 100 000) than blacks (17 per 100 000). Cardioembolic and small vessel infarcts were the two most important identifiable causes of ischemic stroke among black Americans, and most small vessel strokes in blacks can be attributed to hypertension and diabetes.
1.4.4 Hypertension
Hypertension is the most important modifiable stroke risk factor, with an age-adjusted relative risk of approximately 3 and an attributable risk that may be as high as about 50%, depending on age. The risk for stroke increases proportionately with increasing blood pressure, with systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 95 mm Hg constituting a relative risk of approximately 4. Even small improvements in the control of hypertension can reduce stroke risk significantly. In the United States in 2011–2012, 29% of adults aged ≥ 18 years had hypertension, and this was similar among men and women. This figure varied considerably depending on ethnicity and race, with the age-adjusted prevalence being 42.1% for non-Hispanic blacks, 28.0% for non-Hispanic whites, 26.0% for Hispanics, and 24.7% for non-Hispanic Asians. Hypertension increases with age, and according to estimates in the United States in 2011–2012, in adults aged ≥ 60 years the prevalence was 65.0%. The percentage of those with hypertension controlled to a blood pressure of o140 mm Hg systolic and <90 mm Hg diastolic was <50%.
1.4.5 Diabetes Mellitus
Diabetes mellitus is a potentially modifiable risk factor with a relative risk of ischemic stroke of 1.8–3.0. In the United States in 2012, 29.1 million inhabitants had diabetes, of which 21.0 million were diagnosed and 8.1 million were undiagnosed. The rates of diagnosed diabetes varies in different subgroups of the population and was 15.9% for American Indians/ Alaskan Natives, 13.2% for non-Hispanic blacks, 12.8% for Hispanics, 9.0% for Asian Americans, and 7.6% for non-Hispanic whites. Diabetes is associated with the development of atherosclerosis, hypertension, obesity, abnormal blood lipid levels, and ultimately stroke.
1.4.6 Smoking
Active cigarette smoking has been attributed to causing approximately 18% of ischemic strokes, and the risk increases twofold among heavy smokers compared with light smokers. Former smoking has an attributable risk of 6%, with the level of risk varying according to the time since quitting, and major risk reduction occurs within 2–4 years of smoking cessation. Cigarette smoke may enhance platelet aggregation, increase coagulability, blood viscosity, and fibrinogen levels, and raise blood pressure.
1.4.7 Previous Stroke
Previous stroke is a major risk factor. The cumulative risk for recurrent stroke is 3–10% in the first 30 days and 5–14% in the first year. The 5-year estimated recurrence rate is 25–29% or higher.
1.4.8 TIA
TIA is a significant independent risk factor for ischemic stroke and has an average annual risk of approximately 4%. The greatest risk is in the first year following a TIA. In addition to TIA, the presence of other risk factors, including older age (>60 years), diabetes mellitus, duration of a TIA event >10 minutes, and signs or symptoms of weakness and speech impairment TIA, TBI, and Ischemic Stroke: Risk Factors and Treatments 5 are associated with increased risk of subsequent stroke. Half of all strokes occur within 23 days of the TIA, and the 90-day stroke risk is 11%.
1.4.9 Atrial Fibrillation
The risk of stroke in patients with non-valvular atrial fibrillation is approximately 3–5% per year, and approximately two-thirds of strokes are cardioembolic. Factors that increase risk in patients with atrial fibrillation include older age, prior TIA or stroke, hypertension, impaired left ventricular function, and diabetes mellitus. Atrial fibrillation is implicated in approximately 24% of strokes in patients aged 80–89 years.
1.4.10 Atherosclerosis of Carotid Arteries
Atherosclerosis of carotid arteries is implicated in 20–30% of ischemic strokes. Both TIA and ischemic stroke are more frequent in patients with severe carotid artery stenosis (>75%), with an annual risk of 3% in those with 60–90% stenosis.
1.4.11 Coronary Artery Disease
In the Framingham study, ischemic stroke occurred in 8% of men and 11% of women within 6 years of an acute myocardial infarction. Coronary artery bypass procedures and open heart surgery carry a risk of stroke, and perioperative stroke occurs in 1–7% of patients undergoing cardiac surgery.
1.4.12 Obesity
Obesity and in particular abdominal obesity are associated with greater stroke risk, with the risk rising as body weight increases. The relative risk in overweight women ranges from 1.8 for a body mass index (BMI) of 27–29 kgm-2 to a risk of 2.4 for a BMI of ≥ 32 kgm-2.
1.4.13 Diet
Increased salt intake is associated with hypertension, and a decrease in salt intake may lower both blood pressure and the associated stroke risk. A higher cereal fiber intake has been associated with a lower risk of total stroke and ischemic stroke.
1.4.14 Physical Activity
Physical activity reduces the risk of cardiovascular disease. Light to moderate physical activities such as walking, jogging, and swimming provide a stroke reduction benefit. Physical exercise may also have a beneficial effect on other risk factors, such as body weight and blood pressure.
(Continues…)
Excerpted from "Acute Brain Impairment"
by .
Copyright © 2018 The Royal Society of Chemistry.
Excerpted by permission of The Royal Society of Chemistry.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.