Neurology 2: Stroke Portal
A stroke occurs when a vascular blockage or intracranial bleeding disrupts the blood supply to the brain. Brain cells can die rapidly from lack of oxygen and nutrients caused by the sudden prolonged decrease in blood flow and resulting lack of oxygen. Stroke is referred to as a brain attack and is the third leading cause of death in the United States and the leading cause of adult disability.1 Rapid recognition of symptoms and transport to a stroke center/facility that is certified as "stroke ready" is essential to save lives and prevent disability. Time is brain and lost time is lost brain. It is important to have treatment protocols established and to follow clinical pathways. There are two types of stroke: those caused by a blockage of blood flow (ischemic) and those caused by bleeding (hemorrhage).
An ischemic stroke is the most frequent type of stroke and is responsible for over 80% of strokes.2 Ischemic strokes occur when arteries are blocked by blood clots or by the gradual build up of plaque or other fatty deposits. An ischemic stroke can be caused by an embolism or a thrombus.
An embolism is the movement of a clot from another part of the body, such as the heart, to the neck or brain. It usually occurs in a large vessel due to a blood clot, from another site, occluding the vessel. This causes a white infarction (non-hemorrhagic) initially. However, the embolus can break off into smaller pieces and partially restore perfusion to the brain (but also may lead to other stroke symptoms as it travels down the blood vessel). This may later result in an open artery and the development of a hemorrhagic or red infarction. Embolic strokes account for 30% of ischemic strokes.3
A thrombosis is the formation of a clot within a blood vessel of the brain or neck. This forms a white infarct (non-hemorrhagic) of dead CNS tissue, due to large vessel disease and accounts for approximately 50% of ischemic strokes. Thrombosis in large vessels is the most common and is often associated with coronary artery disease. Small vessel thrombosis is referred to as lacunar infarction and is closely linked to hypertension. Lacunar infarctions (little lakes) are < 1 cm. These are secondary to hypertension (particularly if poorly controlled) where the significant increase in BP causes the arterial wall to hypertrophy and result in choking off or closing the vessels.
Biochemistry and Physiology of Ischemic Stroke: The extent of brain injury in ischemic stroke is determined by the duration and degree of ischemia. Diminished cerebral blood flow triggers a cascade of events that includes defective protein synthesis, increased lactate production, glutamate release, depletion of ATP stores, and calcium influx into cells. The lactic acid is toxic to neurons. Excitatory amino acids (EAA) are released during cerebral ischemia. Glutamate is one of these excitatory amino acids that are released from astrocytes and presynaptic neurons. The glutamate interacts with N-methyl-D-aspartate (NMDA) receptors, triggering a cascade of calcium influx and activation of a host of intracellular enzymes (including lipases) which leads to cell death.
Hemorrhagic stroke is the second most common type of stroke and is responsible for about 16% of all strokes. Hemorrhagic strokes are responsible for more than 30% of the deaths due to strokes. Hemorrhagic stroke occurs when a vessel in the brain ruptures and bleeding occurs into the brain or the spaces surrounding the brain.3
Two Types of Hemorrhagic Strokes
Intracerebral
Hemorrhage is a stroke where the cerebral vessel ruptures and causes
bleeding into the brain. These are usually associated with
hypertension, amyloid, or a vascular malformation. Sudden onset is
common with this type of stroke. The symptoms vary according to the
amount of bleeding and the location of the brain involved and may
include: loss of consciousness, vomiting or severe nausea, severe
headache with no other known cause, sudden numbness or weakness of
face, arm or leg (especially on one side of the body)
Treatment of an intracerebral hemorrhage can include both medical and surgical interventions depending on the cause and the size of the bleed. Consult with your stroke center or neurologist for treatment recommendations.
Statins are used widely for both primary and secondary prevention of ischemic cardiac and cerebrovascular disease. However, a recent clinical trial4 suggests an increased risk of intracerebral hemorrhage ICH associated with statin use in patients with previous stroke or TIA. Consider avoiding statin use in patients who have baseline elevated risk of ICH, particularly those patients who have a previous ICH.5
Subarachnoid hemorrhage can have a variety of causes but usually occurs when an aneurysm bursts in a large artery on or near the thin, delicate membrane surrounding the brain. Blood spills into the area around the brain which is filled with the cerebral spinal fluid. This causes the brain to be surrounded by blood-contaminated fluid. More than half of SAH are caused by the rupture of an aneurysm.
Typically there are no warning signs unless there has been a "warning leak" with a resultant headache. Other symptoms include sudden, severe headache (“worst headache of their life"), stiff neck, nausea or vomiting, light intolerance, and loss of consciousness.
Treatment includes surgery to clip the aneurysm on the outside or to use endovascular embolization. During this procedure a metal coil is inserted through a catheter inserted through the femoral artery in the inguinal area. Clipping or embolization of the aneurysm is done to prevent additional bleeding.
A transient ischemic attack (TIA) is sometimes called a “mini-stroke” since the stroke symptoms disappear on their own in a short period of time (< 24 hours). The typical TIA resolves gradually over 15 to 30 minutes. The majority of TIA patients have resolution of their symptoms within 1 hour, although by definition, the symptoms can last as long as 24 hours. If symptoms last from 1 to 3 days, they are sometimes classified as reversible neurologic deficits. If neurologic symptoms last for only a few seconds, the episode is not considered a TIA. The symptoms of a TIA are the same or similar to stroke symptoms.
TIAs and ischemic stroke represent 2 points on an ischemic continuum of similar pathophysiology. TIAs are risk factors for an ischemic stroke and a patient with a TIA should receive a full medical evaluation for stroke to identify the underlying cause of the stroke symptom. An estimated 35% of patients presenting with a TIA will go on to have a full blown stroke within a year.3
Pseudo-strokes are non-strokes which manifest rapid neurologic deficit progression and therefore mimic a stroke. These account for 2% to 3% of strokes. Causes of pseudo-strokes are included in the differential diagnosis of a stroke/TIA.
Differential diagnosis of a stroke/TIA:
- Ischemic–atherothrombotic stroke due to a narrowed vessel becoming occluded with a thrombus
- Ischemic-embolic stroke due the embolization of a clot from some source outside of the brain
- Intracranial hemorrhagic stroke due the bleeding of a cerebral vessel bleeding within the brain
- Intracranial hematoma such as an epidural, subdural, or subarachnoid hematoma
- Systemic condition causing a focal neurologic deficit such as hypoglycemia, hyperglycemia, or toxin ingestion
- Rapidly progressive tumors, such as gliomas
- Herpes simplex encephalitis that may show rapid neurologic deterioration
- Todd’s paralysis, a temporary post-ictal paralysis
- Migraine with focal deficit
- Meningitis or encephalitis
- Vasculitis
- Septic embolus
The determination on clinical grounds of the cause for an acute neurologic deficit can be difficult. Some clinical clues include:
- Headache may accompany an ischemic stroke, but a severe headache increases the suspicion of intracranial hemorrhage.
- While migraine headache patients may have focal neurologic deficit, for the migraine to be considered a cause of the deficit, the patient should have a migraine history and other conditions must be excluded.
- In general, a hemispheric ischemic stroke does not cause a depressed level of consciousness (LOC) unless it is (1) very large and associated with mass affect, (2) multifocal, or (3) compresses or involves the brain stem and reticular activating system.
-
An intracranial hemorrhage is more likely to result in a
depressed LOC than an ischemic stroke. Thus, when a patient presents
with an acute neurologic deficit associated with a depressed LOC,
consider the following differential diagnosis:
- Large hemispheric stroke with or without mass effect
- Intracranial hemorrhage with or without hydrocephalus
- Cerebellar stroke/bleed/tumor with mass effect and brain stem displacement
- Intracranial mass (tumor)
- Post-traumatic concussion or coma
- Brain stem stroke involving the reticular activating system
- Meningitis/encephalitis
- Toxic metabolic encephalopathy
-
Subarachnoid hemorrhage
- A stiff neck (meningismus) may suggest meningitis or subarachnoid hemorrhage.
- An irregular pulse may indicate atrial fibrillation and thus increase the chance of an embolic stroke.
Assessment of Stroke Patients
Rapid
assessment is essential to identifying a stroke patient. Several stroke
scales are available for public, EMS, and hospital personnel. The type
of stroke (ischemic or hemorrhagic) and the location of the brain
injury determine observable symptoms. The stroke symptoms most commonly
used to assess for stroke include one or more of the following signs
and symptoms:
- Sudden numbness/weakness of the face, arm or leg, especially on one side of the body
- Sudden confusion, trouble speaking or understanding
- Sudden trouble seeing in one or both eyes
- Sudden trouble walking, dizziness, loss of balance or coordination
- Sudden severe headache with no known cause.
Other less common symptoms include:
- Altered LOC, ranging from dizziness to coma
- Difficulty swallowing,a
- Unequal pupils
- Respiratory distress
- Seizures
- Loss of bladder or bowel control
- Nausea and vomiting
The public is now being trained in the FAST scale and encouraged to know the nearest hospital specializing in stroke care.
The FAST scale:
| F= | FACE—Ask the person to smile. Does one side of the face droop? |
| A= | ARM—Ask the person to hold both arms outstretched. Does one side drift downward? |
| S= | SPEECH—Ask the person to repeat a simple sentence. Is their speech slurred? |
| T= | TIME—If anyone experiences any of these symptoms, call 911 and ask to be taken to the neart stroke center hospital. |
EMS professionals are often trained in the pre-hospital Cincinnati Stroke Scale which also uses facial droop, arm drift and speech as determining factors.
The NIH Stroke Scale (NIHSS) is a relatively reproducible and standardized evaluation tool which can be used to help estimate the severity of a patient’s stroke and follow the patient’s progression of improvement or deterioration over time. (Vol III—NEU3 NIH Stroke Scale) Since the NIHSS is standardized and based on objective findings during the evaluation of the patient, repeat evaluations, even if the evaluation is conducted by different observers or in different locations, tend to be reproducible and useful in determining changes in the clinical course of the patient.
The NIHSS can also be useful in the evaluation and decision-making process about the relative risks versus benefits of the use of thrombolytic therapy in the treatment of a patient’s stroke. For example, patients with a higher NIH Stroke Score are at increased risk for an intracranial hemorrhage but may also have the most dramatic positive results from the successful use of thrombolytic therapy. Thus the NIHSS (coupled with other risk factors like increased age, hypertension, atrial fibrillation, coronary heart disease and high cholesterol) is helpful to the provider needing to make a decision about whether thrombolytic therapy should be recommended for use or not. No specific score from the NIHSS determines whether thrombolytics should be used in a given patient. Rather, the decision is made by considering individual information together.
Hospital personnel should be competent in performing the NIHSS. Online training is available at no costs through the American Heart Association (http://www.heart.org), National Stroke Association (http://www.stroke.org), and NINDS (http://intra.ninds.nih.gov) websites.
Treatment of Acute Stroke Patients
- Maintaining and supporting an adequate airway and ventilation is key to the stroke patient’s survival. Both maintaining adequate oxygenation and preventing aspiration are essential. Patients with respiratory insufficiency, who are fighting against a compromised airway, have increased intrathoracic pressure, which results in increased ICP. RSI may be necessary to safely and effectively intubate patients. Etomidate 0.3 mg/kg is useful for sedation because it tends to lower intracerebral pressure. Lidocaine 1.5 mg/kg may help to decrease ICP. Succinylcholine 2 mg/kg is an appropriate paralyzing medication to use.
- Treatment of increased ICP is important. Be sure the airway is maintained; if the patient is intubated, maintain adequate ventilation to prevent hypercarbia. For stroke patients with cerebral edema, giving mannitol 20% IV 250 to 500 cc (rapidly) may be helpful. Hypertonic saline IV has also been utilized for this indication. CALS recommends consultation with a stroke center before using any of the above treatments of increased ICP associated with stroke.
- Maintain adequate circulation. Do not over-hydrate and avoid the use of D5W. Do not over-treat hypertension. (See number 2 below for more on treatment of hypertension in stroke patients.)
Minimize the Damage of the Stroke
- Rule out pseudo-strokes that need treatment, such as herpes simplex encephalitis, tumors, hypoglycemia, or hematomas.
- Treat hypertension in stroke patients carefully. Surrounding the destroyed tissue of a stroke is an area of ischemic brain tissue. If the BP drops, cerebral blood flow decreases and oxygenation to these marginal tissues occurs. Therefore in strokes, unless the BP is very high, it is better not to lower BP. In patients with ischemic stroke who are candidates for alteplase (t-PA), blood pressure should be brought down to 185/110. In patients with ischemic stroke who will not be getting fibrinolytics, blood pressures ≤ 220 systolic and ≤ 120 diastolic may be tolerated unless end-organ damage (for example, MI, aortic dissection, CHF) is occurring. Agents that may cause a dramatic drop in blood pressure, like sublingual nifedipine, should not be used. For patients who have an intraparanchymal intracerebral hemorrhage, there is not total agreement as to the correct BP treatment. If an increase of ICP has occurred, it takes a higher MAP to perfuse the brain. Therefore for patients with intracerebral hemorrhage, if the BP is < 180/105, no treatment is recommended. If the BP ranges from 180 to 230 over 105 to 120 and persists for longer than 1 hour, then treatment may be initiated with oral labetalol or captopril. Labetalol 20 mg IV every 10 to 20 minutes may also be used. If the BP is > 230/120 for longer than 20 minutes, give labetalol 20 mg IV every 10 to 20 minutes. If the diastolic BP is > 140, then begin nitroprusside infusion IV. If decreasing the BP worsens the patient's neurologic deficit or mental status, decrease or discontinue the nitroprusside infusion.
- Fibrinolytic therapy aims to re-cannulize cerebral vessels in order to re-perfuse ischemic brain tissue. Studies have restricted patient entry to treatment with t-PA within 3 to 4.5 hours of stroke onset.b Time is brain, so earlier is better. Treat patients as early as possible. Despite a small risk of serious brain hemorrhage with t-PA, t-PA has been shown to improve clinical outcomes when used for acute ischemic stroke. The NINDS study found patients treated with t-PA were 33% more likely to have minimal or no disability after 3 months. This was as compared with patients given placebo. t-PA (Alteplase) is the only approved fibrinolytic for use in ischemic stroke. Baseline CT brain scans should show no hemorrhage or significant early infarction signs. The presence of early infarction signs on CT scan suggests significant ischemic injury, and these patients are at increased risk for hemorrhage if treated with fibrinolytic agents. Streptokinase studies found that the risk of brain hemorrhage outweighed the clinical benefits. Consult with a neurologist or stroke center expert for guidance with acute stroke management involving decisions to use t-PA. If you are transferring to a stroke center, the window of opportunity may be extended if interventional options are available. (See below for a more detailed discussion of the use of fibrinolytic therapy in the treatment of ischemic strokes.)
- Interventional Drug Therapy. Stroke centers are also using t-PA intra-arterially. The drug is administered directly at the thrombus or embolus site in the artery. This can increase the treatment opportunity to 6 hours. Directing the drug at the site also decreases the amount needed and thus reduces the risk of intracranial hemorrhage.
- The MERC I Retriever received FDA approval in 2004. The MERC I Retriever is an endovascular embolectomy device that can restore vascular patency of the ischemic stroke patient within 8 hours of the presentation of stroke symptoms. The catheter has a coiled tip that is used to grasp a clot and remove it from the brain of patients with ischemic stroke.
- The Penumbra System, available since the beginning of 2008, can be used up to eight hours following the onset of symptoms. In ischemic strokes, the Penumbra System uses suction to remove blood clots from the brain. It also allows for safe revascularization of occluded vessels following an ischemic stroke.
- Avoid excess glucose in stroke patients. Hyperglycemia causes ischemic brain tissue to form lactic acid from the glucose, and this is toxic to the ischemic brain tissue surrounding the infarcted tissue. Obtain a glucose level on arrival. Treat blood glucose levels 140 to 185 mg/dL with insulin. If the patient is hypoglycemic, bolus with 50% dextrose.
- Avoid hyponatremia since it may accelerate cerebral edema.
- Consider heparin IV therapy for strokes in evolution, large vessel atherothrombotic disease in the vertebral basilar region, and non-massive cardioembolic strokes. Low molecular weight heparin has been useful in ischemic strokes when initiated within 48 hours after the onset of the stroke.
- Neuroprotective therapy may allow brain tissue to withstand ischemic conditions for a longer period of time before developing irreversible neuronal injury. The amino acid glutamate appears to be a key mediator of ischemic injury. Therefore, drugs that interfere with glutamate transmission or other biochemical reactions that occur during ischemic neuronal injury may have substantial neuroprotective effects. Many medications are being tested for this purpose. (Neuroprotection has not been the panacea that was forecast years ago. However, they still keep trying. You might want to keep this in as a treatment goal – but therapies have been slow to come into practice.)
t-PA Therapy for Acute Ischemic Stroke
In adults, t-PA is indicated for the management of acute ischemic stroke for improving neurological recovery and reducing the incidence of disability. Initiate treatment only if the time since the onset of the patient’s stroke symptoms is less than 3 hours and after exclusion of intracerebral hemorrhage by a cranial CT scan or other diagnostic imaging method sensitive for the presence of hemorrhage. (See Contraindications for Use of t-PA below.)
Patient Selection
- Patient must be seen within 3 hours (in selected cases, within 4.5 hours) of onset of acute ischemic stroke symptoms.
- Obtain baseline brain CT to exclude intracerebral hemorrhage/ other risk factors.
- Review patient history for potential contraindications.
- The patient’s age must be 18 years or older.
Contraindications for Use of t-PA
- Evidence of intracranial hemorrhage on pretreatment evaluation
- Suspicion of subarachnoid hemorrhage
- Recent intracranial surgery
- Serious head injury or stroke within the past 3 months
- History of intracranial hemorrhage
- Uncontrolled hypertension at the time of treatment (eg, > 180 mm Hg systolic or > 110 mm Hg diastolic)
- Arterial puncture at noncompressible site in the past 7 days
- Active internal bleeding
- Intracranial neoplasm, arterial venous malformation, or aneurysm
- Blood glucose < 50 mg/dL
- Multilobar infarct on imaging
- Known bleeding diathesis, including but not limited to
- Current use of oral anticoagulants, such as warfarin with a PT > 15 seconds (INR > 1.7)
- Administration of heparin within 48 hours preceding the onset of the stroke and an elevated PTT at presentation
- Platelet count < 100 0003
Relative Contraindications
- Minor or rapidly improving stroke symptoms
- Seizure at stroke onset with residual neurologic symptoms
- Major trauma or surgery within 14 days
- Gastrointestinal or genitourinary hemorrhage within 21 days
- MI within 3 months
- Post-MI pericarditis
Warnings
Patients who exhibit severe neurological deficits are at increased risk
of intracranial hemorrhage with the use of t-PA.
Patients
with major early infarction signs on CT scan (such as substantial
edema, mass effect, or midline shifts) are at increased risk for the
use of t-PA with acute ischemic stroke.
Dosing Information for t-PA Use
Total dose is 0.9 mg/kg IV with a maximum dose of 90 mg. Administer 10% of this total dose as an IV bolus over the first minute. Infuse the remaining 90% over the following 60 minutes.
Follow-Up
Monitor vital signs and neurologic status. Maintain BP <
180/< 110 mm Hg.
No anticoagulant or anti-platelet therapy for 24 hours
New CVA Prevention Requires Identification and Treatment of Risk Factors
- Treat hypertension aggressively.
- The patient must stop smoking cigarettes.
- Consider anticoagulation for patients with atrial fibrillation. Geriatric patients with atrial fibrillation have an increased risk of embolic stroke.
- The effect of lowering elevated cholesterol in the prevention of stroke is controversial. Hemorrhagic stroke seems to be increased for patients with a cholesterol level < 160. Cholesterol levels > 240 are associated with an increased incidence of ischemic stroke. Statin drugs do decrease the incidence of strokes when given to patients with arteriosclerotic heart disease but do not seem to decrease incidence for patients without this disease. For patients with carotid plaque formation, statins do decrease carotid plaques; but whether statins decrease stroke risk is questionable, unless the patient has arteriosclerotic heart disease.
- Manage patients with diabetes carefully, although there is some controversy in the optimal level of blood sugars for stroke prevention.
- Carotid endarterectomy is helpful for patients who have TIAs and a carotid stenosis > 70%. If the patient has a TIA and a carotid stenosis of < 30%, carotid endarterectomy is not helpful. For patients with a 30% to 70% stenosis and a TIA or stroke with symptoms that match the distribution of the stenotic carotid, endarterectomy is controversial but may be helpful if the patient's life expectancy is longer than 2 years.
Cause of Death, Post Stroke
- Respiratory insufficiency: either due to CNS bulbar dysfunction with resulting hypoxia and hypercapnia or the inability to protect the airway from secretions with resulting aspiration
- Increased ICP from brain swelling or edema: This is particularly present with intracerebral hemorrhage but may occur with large cerebral ischemic strokes. This cerebral edema may result in brain herniation. The cerebral edema usually becomes manifest 24 to 36 hours after the stroke. First, the patient becomes drowsy as the ICP increases. Later, localized neurologic symptoms become apparent. Third nerve findings follow the drowsiness and may initially be subtle with only slight asymmetry of the pupils or mild sluggishness of the reactivity of the pupils. Later, the patient may develop bilateral neurologic findings, such as bilateral up-going toes as the brain stem is involved. Papilledema is a late finding of increased ICP and does not occur for at least 12 hours after the ICP rises significantly. As a rule, you see pupillary changes prior to eye deviation or a totally blown pupil. CT scanning may be necessary to evaluate for increased ICP.
- Intracerebral hemorrhage has a higher mortality than ischemic stroke. The increased incidence of increased ICP, greater brain destruction, and the risk of recurrent bleeding after the initial bleed all contribute to this increased mortality associated with hemorrhagic strokes. There are many new interventional procedures available at Primary Stroke Centers and help to reduce the mortality of patients with hemorrhagic strokes.
- Underlying cardiovascular disease is common for patients who have strokes. Many stroke patients die from MI or arrhythmias. Risk of recurrent strokes increase in patients with atrial fibrillation (10% of strokes are from AF).
- Infections—such as pneumonia and especially aspiration pneumonia or urosepsis contribute to the deaths of stroke patients.
- Missed pseudo-strokes, many of which are potentially treatable, are another cause of death post stroke.
References
- Early Intervention in the Treatment of Stroke. Post Graduate Medicine. McGraw-Hill Companies, Inc, 1997.
- National Institute of Neurological Disorders and Stroke. Available at http://intra.ninds.nih.gov. Accessed July 24, 2008.
- National Stroke Association. Available at www.stroke.org. Accessed July 24, 2008.
- Amarenco P, Bogousslavsky J, Callahan A III, et al: Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549-559.
- Westover MB, Bianchi MT, Eckman MH, Greenberg SM. Statin use following intrancerebral hemorrhage: a decision analysis. Arch Neurol. 2011;68(5):573-579.
- Turner-Lawrence DE, Peebles M, Price MF, Singh SJ, Asimos AW. A feasibility study of the sensitivity of emergency physician dysphagia screening in acute stroke patients. Ann Emerg Med. 2009;54:344-348, 348.e1.
- Werner H, Kaste M, Bluhmki E, et al; ECASS investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Eng J Med. 2008;359:1317-1329.
- Wahlgren N, Ahmed N, Davalos A, et al; SITS investigators. Thrombolysis with alteplase 3-4.5 h after acute ischemic stroke (SITS-ISTR): an observational study. Lancet. 2008;372:1303-1309.
- Ahmed N, Wahlgren N, Grond M, et al; SITS investigators. Implementation and outcome of thrombolysis with alteplase 3-4.5 h after an acute stroke: an updated analysis from SITS-ISTR. Lancet Neurol. 2010;9:843-845.
Other Resources
- Minnesota Department of Health. A new Minnesota Stroke Registry will have stroke outcome data (in the future). www.mnstrokepartnership.org
- American Heart Association/American Stroke Association—various stroke management guidelines, www.strokeassociation.org
- Minnesota Stroke Association (chapter of NSA). Patient information materials and state resources. Available at http://www.strokemn.org. Accessed July 24, 2008.
- Hazinski MF, Field JM, Gilmore D, editors. Handbook of Emergency Cardiovascular Care. Dallas, TX: American Heart Association, 2010.