Definition and Causes:

Sudden loss of brain function due to reduced or complete blockage of blood flow to the brain or bleeding in the brain leading to the death of the brain cells in the affected area.

There are 2 major types of stroke:

A) Ischemic (non-bleeding) stroke:

Accounts for approximately 80-85% of all strokes. Blood supply to the brain comes directly from the heart and is pumped up into the brain through blood vessels called arteries. Obstruction of blood flow with a blood clot within an artery supplying the brain is the most common cause of ischemic stroke. Arteries can become hard with aging and sometimes has plaque buildup (or atherosclerosis) within the vessel walls (think of it as rust within a pipe). Plaques within the arteries can cause the formation of blood clots. During an ischemic stroke blood clots may either form directly within the arteries inside the brain or sometimes blood clots form along the arteries in the neck (two carotids arteries at the front and 2 vertebral arteries), which then dislodges (breaks off) and travel into the brain to block an artery causing a stroke. In other circumstances, clots may form within the heart itself (often associated with an irregular heartbeat called atrial fibrillation), and then travel throughout the heart within the arteries to the brain. When it eventually blocks a blood vessel in the brain an ischemic stroke would occur.

The formation of a clot within the blood vessels is called thrombosis. A clot within the heart or within an artery in the neck, that dislodges and travel into the brain to cause stroke is called an embolus

B) Hemorrhagic stroke:

Refers to bleeding in and around the brain, and accounts for 15-20% of all strokes. As with ischemic (non-bleeding) strokes, brain hemorrhages leads to the death of the brain cells in the affected area.

There are 2 main types of hemorrhagic strokes, usually caused by the defects in the structure of the blood vessels.

• Subarachnoid hemorrhage (SAH): A thin 3-layered membrane called the meninges surrounds the brain. The arachnoid is the middle layer. Rupture of an aneurysm (out-pouching of a blood vessel wall) leads to bleeding under the arachnoid layer overlying the brain

• Intracerebral hemorrhage: The brain has a very rich supply of blood vessels. Rupture of any of these vessels leads to bleeding within the brain tissue

Comparison of Ischemic and Hemorrhagic Stroke

Image showing Blood Vessel rupture and Bleeding

Symptoms:

Stroke symptoms depend on the area of the brain affected and the extent of brain damage. Sometimes small stroke may not cause any symptoms, such strokes are sometimes referred to as “silent strokes”, but they still cause brain tissue damage, which may go unrecognized.

Stroke signs and symptoms:

• Sudden weakness of the face, arm, or leg, especially on one side of the body. May lead be seen as drooling due to facial weakness, or difficulty moving an arm or a leg. Walking may become unsteady
• Sudden numbness (loss of sensation) of the face, arm, or leg, especially on one side of the body. Loss of sensation to sharp objects such as a pin
• Trouble speaking or understanding
• Loss of vision problems in one or both eyes
• Sudden difficulty walking (with or without weakness)
• Dizziness in association with weakness, numbness, speech, or swallowing difficult. Dizziness or vertigo without other neurological symptoms, and particularly if made worse by head movements might suggest inner ear dysfunction rather than a stroke
• Sudden explosive headache that comes on within seconds might suggest an aneurysm rupture. Gradual onset, severe headache that comes on over minutes are often due to migraine or other type headaches. However, seek medical attention if concerned

Note: Strokes occur suddenly and so too do the symptoms i.e. gradual worsening of symptoms may suggest some other process rather than a stroke. Again, always seek medical advice if in doubt.

Investigations and Treatment:

A detailed history will be obtained and a physical examination will be performed. The time of onset of the symptoms should be noted as this is important for using clot-busting agents for treating acute ischemic stroke.

INVESTIGATIONS:

There is a very narrow time window (less than 4.5 hours from onset of symptoms) to intervene in an acute ischemic stroke with medications to reverse the loss of blood supply to the affected part of the brain. Patients or family members/friends should call emergency medical services promptly for transport to an emergency room equipped to handle acute stroke.

Investigations for emergency cases:

Most commonly used investigations in the ER when clot-busting drugs are being considered include:

• Blood work
• Electrocardiogram (ECG)
• Computed tomography (CT) scan of the brain: Used to visualize the brain and exclude bleeding or other conditions (e.g. tumors). This device uses x-rays. Patients will lie on a table with the head placed inside of the scanner (resembles a large donut). Computer analysis of X-ray images produces detailed images of the brain. The scanning time is usually very rapid (less than 1 minute). The scan is done to exclude hemorrhages and other conditions (e.g. tumor) that might be causing the patient’s symptoms

• Note: Most CT scans of the brain, completed in the first 2-4 hours following an ischemic stroke, would appear normal.

Other commonly used investigations that may be done after initial ER investigations include:

Magnetic resonance imaging (MRI):

• MRI uses magnetic fields over the body to produce images. The device looks like a long cylindrical tube. The patient lies on a table that slides into a hollow tube. Computer analysis of the magnetic fields generates images of the internal structures of the body, including the brain. In stroke patients, the MRI brain shows the normal structures, plus any area(s) of brain injury. MRI takes 30-60 min. In some circumstances, a dye may be injected into the veins (enhanced MRI) just before the scan to help improve the detection of abnormalities. Patients who complain of claustrophobia or discomfort may be given a mild sedative to help relax prior to MRI scanning

CT-angiogram (CTA) and MR- angiogram (MRA):

• Imaging techniques in which a dye is injected into the vein and a CT scan or MRI is performed while the dye is flowing in the blood vessels. Detailed images of the blood vessels are produced by computer analysis. In stroke patients, CTA or MRA is used to assess blood vessels in the neck and brain. CTA and MRA can show narrowing, blockages, dissections (a tear) within the vessels and aneurysms (pouches) on blood vessels

Carotid doppler:

• Ultrasound imaging of the neck, helpful in assessing blood flow in neck vessels

Holter monitor:

• A small portable device that can be fixed on the chest and records the electrical activity of the heart. Used to monitor heart rate for 24-72 hours

Cardiac ECHO:

• Imaging technique that uses ultrasound waves to generate an image of the heart; helpful in assessing the function of all chambers individually

CT and MR perfusion:

• Emerging investigative tool that might distinguish potentially unaffected brain tissue from fully injured areas and might assist in the decision to treat with clot-busting agents or clot retrieval devices

TREATMENT:

An acute stroke is an emergency situation where the time factor plays a major role in deciding which treatment should be given. When available, specially trained stroke teams are mobilized to assist with the management of acute stroke.

Treatment depends on:

1. Type of stroke (ischemic or hemorrhagic)
2. Duration of symptoms (event occurred less than 4.5 hours ago or more than 4.5 hours)
3. Severity of stroke symptoms (unchanged, improving or worsening)
4. What caused the event? (risk factors and associated medical conditions considered)

Treatment strategy for ischemic stroke:

A) Tissue plasminogen activator (tPA):

• A CT scan must be done to see whether the stroke is from a clot or from bleeding
• tPA is a drug used to dissolve the clot that is blocking the blood flow. The time frame to intervene is 4½ hours from the time symptoms first recognized. For patients who wake up from sleep with symptoms of stroke, the time of onset is considered to be the time the patient was last seen in a normal state
• tPA improves the stroke symptoms in 10-30% of patients, but may also cause intracranial bleeding in 6% of patients and can make the stroke symptoms worse or can cause death. However, the stroke itself can cause death and in studies with tPA, there was no difference in the amount of death caused in those treated with or without tPA, but there was a better clinical outcome in those treated with tPA

Note: If the stroke is caused by bleeding instead of clotting, then clot-busting drugs (tPA) are not used, i.e. contraindicated.

B) Treatment of carotid artery stenosis (narrowing):

• Carotid artery stenosis (or narrowing) is often due to plaque build-up from atherosclerosis (hardening) within the vessel. Blood clots can subsequently form on top of the plaque and can dislodge and go into the blood vessels within the brain, leading to stroke. Carotid Doppler studies as well as CTA and MRA (see above) can be used to assess the degree of narrowing. If the carotid artery is narrowed along the same side as the stroke,i.e. right or left the brain, then opening the vessel either surgically (called carotid endarterectomy) or through balloon angioplasty might be an option. Procedures might be considered for patients with stroke symptoms who have moderate 50-69% or severe greater than 70% narrowing of the carotids. Patients are usually referred to a neurologist to discuss this and assist with deciding on whether the patient may be a good candidate to have the vessel opened and if so, which procedure would be the best option. For patients with stroke due to vessel narrowing, if opening the vessel is advised (based on location and size of the stroke, and other medical factors), the procedure is often performed as soon as possible after the event and usually less than 4 weeks
• Sometimes the vertebral arteries in the posterior neck are narrowed and may be a cause of stroke at the back of the brain or deep brain areas (the brain stem). Surgery is not used in these areas but, angioplasty and stenting is sometimes an option

C) Treatment of asymptomatic carotid artery stenosis:

• If the narrowing of the carotid artery by greater than 60%, is detected on a carotid Doppler study and the patient does not have stroke symptoms, then the vessel is considered asymptomatic (no symptoms) and the annual risk of stroke is low ~2%. Surgically treating these asymptomatic carotid vessels, i.e to remove the plaque, lowers the annual stroke risk from 2% to 1%. Hence, given the very small 1% benefit of surgery, many patients are treated with medical management only. However, in selected cases, surgery might still be an option. This can be discussed with doctors (neurologists, neuro- or vascular surgeons) with expertise in stroke management

Medications to prevent stroke recurrence:

Antiplatelets:

• Antiplatelet agents are medicines used to prevent stroke recurrence by decreasing the formation of blood clots within the blood vessels. Examples include aspirin, Plavix (clopidogrel), Aggrenox, Ticlid (ticlopidine). Patients with acute non-bleeding (ischemic) stroke who are not eligible to receive tPA, are often prescribed antiplatelet drugs (usually aspirin) in the emergency room. Early use of aspirin after the onset of an acute ischemic stroke may have a small, but measurable benefit in reducing stroke recurrence and death. However, depending on the scenario some patients may be prescribed anticoagulants (see below)

Anticoagulation:

• These drugs can prevent the formation and/or expansion of blood clots. While they are often referred to as “blood thinners”, they do not really “thin” the blood, but they do interfere with the body’s ability to form clots. Anticoagulants are used in a situation where there might be a tendency to form blood clots. One such example is the heart condition called atrial fibrillation (AF). This condition becomes more prevalent with aging and associated with high blood pressure, previous heart attack, overactive thyroid, excessive alcohol consumption. In AF the top chambers of the heart (the atria) do not beat in a regular fashion but instead quivers or “fibrillates”. This causes the blood within the atria to pool and clot. These clots then drop into the lower chambers (the ventricles) and are pumped out of the heart. The circulating clots are called emboli. If they get pumped into the brain, they may block a blood vessel and cause a stroke

• AF causes clot formation within the heart. Clots then leave the heart and enter the bloodstream. The circulating clots are called emboli. A clot entering a blood vessel in the brain, can block the blood flow. The lack of oxygen from the stoppage of blood flow causes ischemic (non-bleeding) stroke

• Many patients with AF may be advised by their physicians to use a “blood thinner” i.e. an anticoagulant to prevent the formation of these clots. Intravenous (IV) heparin or low molecular weight heparin (LMWH), which can be injected under the skin, has not been shown to have any impact on reducing strokes caused by AF and is rarely used. The oral agent warfarin is an old drug that has been used for many years to help prevent strokes due to AF. However, it is somewhat difficult to get the blood levels (called INR) correct and so requires frequent blood work for monitoring. A number of different foods and medications also affect blood INR levels. The routine use of warfarin in patients with AF is gradually being replaced by the new anticoagulants including Pradaxa (dabigatran), Xarelto (rivaroxaban), Eliquis (apixaban) and Savaysa (edoxaban), which are just as good or better than warfarin and do not require any blood monitoring

Management of risk factors:

A stroke patient is ~9 times more likely to have a recurrent stroke and ~2.5 times more likely to have a heart attack. Hence it becomes important to affect healthy lifestyle changes including:

• Comply with medications and advice of the healthcare team
• Monitor, manage and control blood pressure and diabetes (if present)
• Treat cholesterol
• Stop smoking
• Lose weight (if overweight)
• Improve diet
• Exercise

Treatment of hemorrhagic stroke:

Subarachnoid hemorrhage (SAH):

• Most commonly caused by an aneurysm. SAH causes a sudden explosive headache. These headaches are instantaneous and can patients often described them as being hit off the head with a baseball bat
• The bleeding from a ruptured aneurysm can range from mild to severe and can lead to coma and death
• Usually investigated with (i) a brain CT scan, (ii) CT angiogram, or (iii)MR Angiogram (see investigations above). A lumbar puncture (spinal tap) is done in some patients to examine for blood in the spinal fluid (which would indicate the likelihood of a SAH)
• Most aneurysms are treated by inserting a thin tube called a catheter into one of the arteries in the groin area and extending it to the site of an aneurysm within the brain. Small coils at the tip of the catheter can be placed within an aneurysm, creating a seal. Procedures using catheters within the blood vessels are called “endovascular surgery”, and have largely replaced the now less commonly used neurosurgical aneurysmal clipping techniques

Non-SAH brain hemorrhage:

• Occurs from the breakage of one of the blood vessels within the brain. Aging and vascular risk factors such as long-standing high blood pressure, smoking, diabetes, cholesterol can lead to hardening and weakening of the small blood vessels with the brain, which can subsequently rupture
• Antiplatelet and anticoagulant (“blood-thinning”) medications (see above), as well as certain medical conditions such as those with low blood platelets, or inflammation of the blood vessels (vasculitis), can also cause hemorrhages
• Brain hemorrhages have higher morbidity (disability) and mortality (death) than non-bleeding ischemic stroke
• There is no specific treatment that is known to arrest bleeding and improve patient outcomes. For those with a hemorrhagic stroke occurring while using “blood thinners” (anticoagulants), attempts have been made to use certain intravenously administered blood products and compounds that promote blood clotting to help limit the bleed and hopefully improve outcome. However, there is no unequivocal data to suggest that this strategy is beneficial
• Treatment is largely supportive, such as controlling and treating blood pressure and blood sugar (in diabetics). Patients may not be able to swallow and so intravenous hydration and feeding tubes used when necessary

Rehabilitation

Once the patient is on the stroke ward, the goal is to maximize the individual’s functional abilities by providing inpatient rehabilitation. For those with minor stroke rehabilitation can also take place in an outpatient setting after discharge. For those with more severe stroke symptoms and slower recovery rehabilitation might be continued in a nursing facility (if available).

The rehabilitation process includes some or all of the following:

• Speech therapy
• Occupational therapy
• Physical therapy
• Family education to orient them in caring for their loved one at home and the challenges they will face

Since stroke leads to the permanent loss of brain cells, many patients do not make a total return to their pre-stroke functional status. Home healthcare advisors (e.g. occupational therapists) can assess the home living situation and make recommendations to ease the transition home.

Unfortunately, some stroke patients have such significant loss of functionality that they require long-term nursing, home care or assisted living.

Long-term treatment:

The goal is to help regain functionality and prevent future strokes. The recovery time and need for long-term treatment are different for each person. Problems moving, thinking, and talking often improve in weeks to months after a stroke.

Long-term problems:

• Persistent weakness
• Impaired balance
• Difficult walking
• Bladder and bowel problems
• Muscle spasms or rigidity (called spasticity)
• Speech problems/ difficulty communicating
• Chewing and swallowing difficulty
• Impaired memory and early dementia

MEDICATIONS

Some commonly used oral medications in stroke are as follows:

Risk Factors and Prevention:

Non-modifiable risk factors:

Age

• Risk of stroke increases with age. The risk of stroke doubles for each decade after the age of 55 and is more prevalent in those over 65 years. However, stroke may occur at any age, even in children

Gender

• Men may have a higher lifetime risk of stroke, but women have the worse outcome from strokes

Family history

• This most often refers to “premature” vascular disease. If parents or siblings sustain a stroke before the age 55yrs; then the risk of stroke is higher as compared to individuals who do not have the stroke in first degree relatives

Ethnicity

• First Nations people and those of African or South Asian descent are more likely to have high blood pressure and diabetes, and are at greater risk of heart disease and stroke than the general population. Hemorrhagic stroke is also more prevalent in some Asian (Oriental) populations

Prior stroke or TIA (transient ischemic attack)

• Previous stroke or a transient ischemic attack (often called “mini-strokes”), increases the risk of recurrent stroke

Modifiable risk factors:

• High blood pressure (hypertension)
• High blood cholesterol
• Atrial fibrillation (irregular heartbeat)
• Diabetes
• Overweight
• Excessive alcohol consumption
• Physical inactivity (sedentary lifestyle)
• Smoking
• Illicit drug use

Outcome:

Most stroke survivors will have varying degrees of recovery. In general better recovery is expected when the stroke is small versus a large stroke. Also, younger patients may recover faster than older patients with the same size stroke. However, the recovery is not predictable in any stroke patient. Some survivors may go on to lead full, meaningful lives.

The stroke outcome therefore usually depends on the following:

• The type of stroke (ischemic vs hemorrhagic)
• How much brain tissue is damaged (small vs large)
• What body functions have been affected (speech loss and paralysis vs numbness)
• Whether patients were treated tPA or not (patient who receives the clot-buster tPA have a better chance of recovery)

Recovery can be near an individual’s pre-stroke status, or there may be some permanent loss of function.

Nearly 50% of stroke patients are able to live independently at home.

The risk of the second stroke is highest during the first 3 months after the first stroke.

Treatment with clot-busting drugs could potentially bring about a full recovery, however, a challenge still remains with patient awareness and getting to the hospital soon enough to be considered for this therapy.

Mortality due to stroke:

Age-standardized case fatality rates are higher for women than for men. After 4 weeks of equally high risk for both sexes, women continue to have a higher risk of death than men for as long as 1 year after the stroke. The excess risk for death does not differ significantly between sexes after the first year.