A stroke is the acute neurologic injury that occurs as a result of impaired blood flow to the brain. It is a devastating disease that effects all people of all ages. It negatively impacts the patient as well as their families and the community in which they live.
Stroke is ubiquitous throughout the world. It is the second leading cause of death worldwide and is the fourth leading medical cause of death in the U.S. and within Georgia. Georgia is located within the “Stroke Belt,” a region in the southeastern United States that has been recognized by public health authorities for having an unusually high incidence of stroke and other forms of cardiovascular disease.
The “Stroke Belt” is usually defined as an 11-state region consisting of Alabama, Arkansas, Georgia, Indiana, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee and Virginia. These 11 states have stroke mortality rates that are more than 10% above the national average.
Overall, there are more than 140,000 deaths each year from stroke; 60% of stroke deaths occur in females and 40% in males. In the United States alone, more than 795,000 people suffer a stroke each year, with a stroke occurring every 40 seconds and death every 4 minutes. These numbers are in parallel to heart attacks, with approximately 805,000 heart attacks each year and one every 40 seconds. Sadly, around 25% of people who recover from their first stroke will have another stroke within 5 years.
In addition to being a leading cause of death, stroke is a leading cause of serious long-term disability. Stroke reduces mobility in more than half of stroke survivors that are over the age of 65. Currently, there are more than 7 million stroke survivors living in United States, and unfortunately, two-thirds of them are disabled. Stroke-related costs are astronomical. In the United States alone, they amounted to nearly $46 billion between 2014 and 2015.
Definition of Stroke
A stroke occurs when the brain is deprived of blood flow, oxygen and nutrients, causing parts of the brain to become damaged or die. The brain is extremely sensitive to this lack of blood flow, known as ischemia, with damage beginning immediately. In one second, 32,000 brain cells die, and within 1 minute of an ischemic stroke 1.9 million brain cells die. As a result, stroke can cause lasting brain damage, long-term disability or even death.
The majority of strokes are from ischemia, which accounts for over 80% of strokes; 20% are due to a brain hemorrhage. Transient ischemic attack (TIA) is defined clinically by the temporary nature of the associated neurologic symptoms, which last less than 24 hours by the classic definition. There are two types of stroke that we classify as either ischemic or hemorrhagic.
An ischemic stroke results from a reduction or complete blockage of blood flow. This reduction can be due to decreased systemic perfusion, severe vessel narrowing (stenosis) or occlusion of a blood vessel. Decreased systemic perfusion can be the result of low blood pressure, heart failure or loss of blood. The main causes of ischemia are thrombosis, embolization and lacunar infarction from small vessel disease.
Symptoms of Acute Stroke
The most common signs and symptoms of a stroke are sudden numbness or weakness in the face, arm or leg, especially on one side of the body. The person may experience sudden confusion, have trouble speaking or have difficulty understanding speech. Sudden trouble seeing in one or both eyes. Sudden trouble walking, dizziness, loss of balance or lack of coordination. Sudden severe headache with no known cause.
The use of the acronym BE FAST is an easy way to remember the signs of stroke and what to do if someone near you is experiencing them. B – Balance, E – Eyes (blurry or double vision, sudden loss of vision), F – Face (drooping or numb), A – Arm Weakness, S – Speech Difficulty (Slurred, hard to understand), T – Time to Call 911 (If a person shows any of these signs or symptoms call 911 immediately).
The National Institutes of Health Stroke Scale/Score (NIHSS) is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The maximum possible score is 42 (severe impairment), with the minimum score being a 0.
Treatment of Acute Ischemic Stroke (AIS)
Stroke is a treatable disease with new technology and devices being developed every year. The most recent advances have evolved over only the last 5-10 years.
An acute stroke is diagnosed by performing a series of tests such as brain imaging, including a magnetic resonance imaging (MRI) or computed tomography (CT) scan, tests of the brain’s electrical activity and blood flow tests. Non-contrast computed tomography (NCCT) is typically the first diagnostic study in patients with a suspected stroke. The main advantages of NCCT are widespread access and speed of acquisition.
The time window for the treatment of an acute ischemic stroke has been extended over the years from originally 3 hours in 1996 to now up to 24 hours from last known well (2018). Timely restoration of blood flow in an ischemic stroke is the most effective way to salvage ischemic brain tissue that is not already infarcted or irreversibly damaged but is vulnerable to being permanently damaged if blood flow is not restored.
Removal of an occlusive intracranial thrombus must be accomplished quickly, since the benefit of reperfusion therapy for ischemic stroke decreases in a continuous fashion over time. One of the most important aspects of treating AIS is determining if the patient is eligible for intravenous thrombolysis and/or mechanical thrombectomy.
Alteplase (recombinant tissue-type plasminogen activator or rt-PA) was FDA approved for the treatment of stroke and has been the standard medical therapy since 1996. Intravenous thrombolytic therapy with alteplase improves outcomes in patients who can be treated within 3 to 4.5 hours from stroke onset and meet additional eligibility criteria. Studies have shown that administration of rt-PA improves outcome when compared to no treatment at all.
More recently, Tenecteplase (TNK) has seen increasing use in the treatment of acute ischemic stroke. A recent study evaluating TNK versus rt-PA showed more patients had successful reperfusion of the involved ischemic territory with TNK. Additionally, TNK resulted in better functional outcomes at 90 days.
In 2019, the American Heart Association (AHA) Guidelines incorporated TNK into the treatment of acute ischemic stroke and state that it may be reasonable to choose Tenecteplase over rt-PA in patients without contraindications for IV fibrinolysis who are also eligible to undergo mechanical thrombectomy. In addition, TNK might be considered as an alternative to rt-PA in patients with minor neurological impairment and no major intracranial occlusion.
Despite increased community awareness of stroke, many patients go untreated, worsening their outcome. Studies show that only 3.4% to 5.2% of patients with a stroke receive rt-PA and nearly one-third of eligible patients do not receive rt-PA. Approximately 25% to 33% of eligible patients do not receive rt-PA. Moreover, residents of the “Stroke Belt” are 31% less likely to receive rt-PA.
Endovascular Acute Ischemic Stroke Treatment (Mechanical Thrombectomy).
Many stroke patients are unable to receive intravenous alteplase because they either present to the hospital more than 4.5 hours after last known normal or have a contraindication to receiving intravenous thrombolysis because of the increased risk of bleeding such as recent surgery, novel oral anticoagulants or elevated INR. Moreover, some may not respond to intravenous thrombolysis. In these patients endovascular stroke treatment is performed.
Intra-arterial, endovascular, therapy is a treatment of AIS that is relatively new and has been shown to be very effective at safely restoring blood flow and improving outcome. The endovascular techniques used for the treatment of AIS continue to improve.
Prior to 2015, endovascular treatment was largely considered a rescue therapy and was not part of the standard of care for the treatment of acute ischemic stroke. Numerous trials have shown that people having an acute ischemic stroke do better when they receive both intravenous rt-PA and endovascular stroke treatment.
In 2015, mechanical thrombectomy was adopted into the American Heart Association/American Stroke Association as a new recommendation based on Class I evidence. Subsequent studies have reinforced the benefit of endovascular stroke treatment, and today’s guidelines recommend that patients should receive endovascular therapy if they meet certain criteria, such as last known well within 6 hours, were functionally independent prior to the stroke and have a significant neurological deficit from a large vessel occlusion (LVO). AHA Guidelines recommend endovascular stroke therapy for patients who are experiencing a severe stroke even if they received intravenous rt-PA.
More recent studies using advanced imaging such as CT Perfusion as an additional inclusion criterion for treating stroke have shown a significant benefit and improved outcome, with endovascular stroke therapy in patients up to 24 hours from last known well. CT Perfusion helps to identify areas of brain that are being impacted by a lack of blood flow but have not been irreversibly damaged (penumbra).
As a result of these studies, there have been recent revisions to the American Heart Association Guidelines for the Early Management of Patients with Acute Ischemic Stroke in 2018 and 2019, officially extending the time-window for treating acute ischemic stroke. In selected patients with AIS who have a large vessel occlusion in the anterior circulation and meet imaging criteria, mechanical thrombectomy is recommended in those who were last known well between 6 to 16 hours and is reasonable to consider in those last known well 16 to 24 hours.
Advances in technology and imaging continue to expand our understanding of acute stroke and as such help us to identify patients who will benefit from endovascular treatment with improved outcomes. Improved catheters and stroke devices have made it easier to access vessels and restore blood flow. Recent advances in artificial intelligence and automated processing of imaging now allow stroke physicians to obtain real-time data on stroke patients remotely.
The treatment of acute ischemic stroke is in constant evolution. Thankfully, with increasing community awareness and stroke reduction measures, the incidence of stroke is declining. Moreover, the treatment of stroke is improving each year and is becoming safer and more effective. Hopefully, together this will allow for many more patients to benefit.
Case representation: A 25-year-old male was at a hardware store with his father and was loading wood onto the roof of his car. His father noticed his son was leaning against the car and not able to tie the rope. His father called 911 and the patient was taken to a local acute stroke ready hospital in Jasper, Ga. The patient was rapidly diagnosed with an acute ischemic stroke.
The patient was unable to speak nor follow commands – an NIH Stroke Score of 7. A non-contrast CT scan did not show a hemorrhage and the patient was administered intravenous alteplase (rt-PA) within 27 minutes of arrival. Advanced stroke imaging that included a CT angiogram and a CT Perfusion was performed and processed on a commercially available automated and integrated software package (VIZ ai). The team at the comprehensive stroke center in Atlanta evaluated the imaging.
The CT angiogram showed the patient had decreased flow in the left middle cerebral artery (image 1) with a large area of brain that had decreased perfusion (image 2; green area) and was at risk of having a major stroke. The patient was transferred to the comprehensive stroke center. On arrival the patient had neurologically declined and was now unable to move his right side; NIHSS 15. A repeat CT scan in the endovascular neurosurgery operating room did not show a hemorrhage. The initial cerebral angiogram revealed complete occlusion of the left middle cerebral artery (image 3).
The patient underwent mechanical thrombectomy, and the blood flow was successfully restored (image 4). The patient was admitted to the Neuroscience ICU and was then discharged to inpatient rehabilitation.
Centers for Disease Control and Prevention. Underlying Cause of Death, 1999–2018. CDC WONDER Online Database. Atlanta, GA: Centers for Disease Control and Prevention; 2018. Accessed March 12, 2020.
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Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke. Stroke. 2019;50:e344–e418.
National Institutes of Health, National Institute of Neurological Disorders and Stroke. Stroke Scale. https://www.ninds.nih.gov/sites/default/files/NIH_Stroke_Scale_Booklet.pdf.
Tissue Plasminogen Activator for Acute Ischemic Stroke. The National Institute of Neurological Disorders and Stroke Rt-Pa Stroke Study Group. N Engl J Med. 1995 Dec 14;333(24):1581-7.
Dr. Stiefel is the Medical Director of Piedmont Atlanta’s Comprehensive Stroke Center and Piedmont Health System’s Stroke Program. He is a fellowship-trained neurosurgeon focusing on cerebrovascular and endovascular neurosurgery and neurosurgical oncology. He specializes in the treatment of vascular disorders of the brain, neck and spine as well as brain tumors. Dr. Stiefel is a nationally recognized leader in endovascular techniques for neurovascular disorders, including the treatment of aneurysms and acute stroke.
Dr. Schuette is a board-certified neurosurgeon at Piedmont Atlanta Hospital who is fellowship-trained in open cerebrovascular and endovascular neurosurgery. He was awarded Subspecialty Certification in Neuroendovascular Surgery by the American Board of Neurological Surgeons. He specializes in the treatment of aneurysms, arteriovenous malformations and ischemic stroke. Dr. Schuette serves as a system stroke quality director for Piedmont hospitals, working to build a world-class team for comprehensive stroke care.