Ischemic Stroke Flashcards
Please read through the case and keep it in mind as you move through this self-learning session. See whether you can identify her anatomic, neurologic, and etiologic diagnoses.
What is a stroke?
Stroke is an injury to the brain caused by interruption of its blood flow (ischemic), or by bleeding (hemorrhagic) into or around the brain. Stroke produces the abrupt onset of focal neurologic deficits that frequently result in permanent disability or death (or they may be reversible, in which case it is called a “transient ischemic attack” (TIA).)
Define transient ischemic attacks
TIAs are defined as the abrupt onset of focal neurological deficits that fully resolve within less than 1 hour. TIAs are an important warning sign for future stroke.
Acute focal neurologic symptoms and signs that resolve completely but take longer than 1 hour to do so are invariably associated with detectable injury on MRI brain scans and thus represent silent strokes. The latter may at times be referred to as Resolving Ischemic Neurologic Deficits (RINDs) and although the clinically detectable neurologic deficit may appear to have resolved the MRI brain scan will show evidence of focal brain injury.
Stroke comes in two flavors, hemorrhagic stroke or ischemic stroke. Hemorrhagic strokes comprise approximately 20% of all strokes and may be caused by bleeding into the parenchyma of the brain (intracerebral hemorrhage) or bleeding around the surface of the brain (subarachnoid hemorrhage). Intracerebral and subarachnoid hemorrhages occur in roughly equal proportions.
Ischemic stroke accounts for the great majority of strokes. Ischemic stroke may occur as a consequence of atherosclerotic occlusion of an intra- or extracerebral blood vessel, as the result of an embolus (blood clot) traveling to the brain from either the heart or a cerebral blood vessel, or from disease of the lumen of small arterioles (lacunar infarcts). Also note that a sizable proportion of ischemic stroke is cryptogenic, i.e. the etiology of the stroke is undetermined.
The slide presents CT scans of intracerebral hemorrhage on the top left (note the blood seen as the bright white area in the basal ganglia) and
subarachnoid hemorrhage in the lower left scans (note the blood in the basilar cistern around the midbrain seen as a star shaped silhouette).
The upper right figure is a digital subtraction arteriogram showing an atherosclerotic plaque in the internal carotid artery (red arrow), the middle figure depicts an embolus occluding the lumen of the middle cerebral artery, and the lower figure presents a coronal section through the pons showing a lacunar infarct in the mid-pons (yellow arrow).
In the U.S. and developed countries, stroke is the third leading cause of death and the leading cause of adult disability. Approximately three quarters of a million U.S. citizens suffer a stroke each year. While stroke is predominantly a disorder of the elderly, there are significant numbers of young individuals who suffer a stroke, e.g. the case presented at the beginning of this self-learning session.
This slide presents the death rate from stroke in the U.S. that is adjusted for age. Note the extremely high mortality rate, reflective of stroke incidence, in the Southeast. This area of the country has become euphemistically known as the “Stroke Belt”. Note that the numbers within the state borders represent the national ranking with South Carolina having the highest death rate, and Arkansas and Tennessee following immediately behind.
What are the non-modifiable risk factors for stroke?
These risk factors include age, gender, race, and family history (genetics).
Stroke incidence doubles for each decade above age 55, men have approximately a 1.5 higher stroke incidence than women, and African Americans carry a twofold greater stroke risk than European Americans.
What are the modifiable risk factors for stroke?
- Hypertension
- Diabetes
- Hyperlipidemia
- Smoking
- Carotid artery stenosis
- Atrial fibrillation
- Obesity/Physical inactivity
This slide attempts to depict the relationship between comparative (relative) risk and the prevalence of individual risk factors.
The combination of the two factors determines the quantitative impact on the population. Thus although the relative risk of stroke from atrial fibrillation is extremely high (5-17 fold), its prevalence is comparatively low and its impact on stroke incidence is diminished. In contrast the relative risk of hypertension is lower (3 – 5 fold) but its prevalence is very high in the population; thus hypertension is the number one risk factor for stroke.
The pathological consequence of focal brain ischemia is a cerebral infarct. Infarction being defined as the focal necrosis of all cellular elements of brain, i.e. neurons, glia, and other supporting brain cells.
It is important to distinguish cerebral infarction from another type of ischemic brain injury called:
‘selective ischemic necrosis’ where only brain neurons are injured. Selective ischemic necrosis is encountered most commonly in patients suffering transient global brain ischemia from cardiac arrest and successful cardiac resuscitation. Selective ischemic necrosis affects only specific populations of highly vulnerable neurons, e.g. the CA1 pyramidal neurons of the hippocampus or the cerebellar Purkinje cells of the cerebellum.
In normal conscious man, brain activity consumes approximately 1000 umole of high energy fuel per 100 gm of brain every minute. If one totals up all of the high energy stores in brain in the form of ATP, PCr, glucose, and glycogen one finds that brain energy stores are very meager. In fact, in the absence of the blood supply providing glucose to the brain, each 100 gm of brain has sufficient energy stores to last only two and one-half minutes.
This slide depicts a normal neuron during normal oxygenated metabolism in the upper box and an ischemic or hypoxic neuron in the lower box. Describe the normal conditions
Under normal conditions the mitochondria function to generate adequate ATP and PCr to sustain the membrane ion pumping mechanisms that maintain the fluctuating membrane ion gradients and membrane potential associated with normal depolarization and repolarization.
However, within minutes of the loss of the blood supply (ischemia), what happens to brain energy stores?
They are depleted through the metabolism of glucose via glycolytic pathways with the accumulation of lactic acid (lower box).
If this condition is not rapidly reversed, catabolic mechanisms are triggered and the cell will die.
T or F. Elevated brain temperature will accelerate this process of neuronal ischemic cell death and exacerbate stroke brain injury.
T. Likewise, elevated brain glucose/glycogen stores or elevated circulating glucose will provide further fuel for glycolysis resulting in higher concentrations of lactic acid that also exacerbate ischemic brain injury. Accordingly, a goal for acute stroke intervention is to normalize elevated body temperatures and to rapidly treat hyperglycemia.
This slide depicts the left hemisphere of a human brain with the pre-rolandic branch of the middle cerebral artery occluded by an embolus.
The downstream area of the brain distal to the embolus has experienced reduced blood flow. Note that the reduction of blood flow to this territory is not uniform. The center of the territory, i.e. the area most remote from surrounding blood vessels that may provide collateral blood flow to the area, experiences the most severe loss of blood flow while the more peripheral areas suffer a less severe blood flow reduction. What are these regions called?
The central area with severe blood flow reduction is called the ‘ischemic core’ and the peripheral areas with less severe ischemia is called the ‘ischemic penumbra’.
The clinically relevant aspect of this information is that the ischemic core suffers irreversible injury within 1 hour or less while the area of the ischemic penumbra may survive for several hours. Thus, acute intervention that restores blood supply to this territory has the potential for salvaging brain tissue otherwise destined to die.
This pathophysiology of focal brain ischemia and the temporal profile of the evolving ischemic infarct represents the basis for acute stroke intervention having a therapeutic window of 4 to 6 hours.
This slide summarizes important aspects of the autoregulation of cerebral blood flow (CBF). CBF measured in ml/100 gm brain/min is proportionally related to:
the mean arterial pressure (MAP) divided by the cerebral vascular resistance (CVR).
The slide presents CBF on the vertical axis and MAP on the horizontal axis. Note the relationship between CBF and MAP for the normal individual (shown in red) is a sigmoid curve with a virtual plateau of CBF existing between MAPs of 55 and 155 mm Hg. Thus in this range of MAPs, CBF is relatively constant, i.e. it is independent of MAP. This is important since MAP can fluctuate rapidly and widely with changing position; thus CBF does not fluctuate with body position changes in normal individuals.
Note that when the MAP falls below 55 mm Hg or climbs above 155 mm Hg, CBF then becomes proportionately related to MAP. Thus severe hypotension leads to reduced CBF and syncope. Likewise, elevation of MAP above 155 mm HG may cause hypertensive encephalopathy.
Now note that in individuals with chronic hypertension, i.e. elevated blood pressure for more than two weeks, the CBF curve is shifted to the right. The critical point at which CBF becomes proportionately related to MAP has been raised from 55 to approximately 75 mm Hg. Thus less severe hypotension or even levels of BP that would be considered normal can now result in decreased CBF.
Since the majority of patients that present with a stroke are hypertensive, i.e. they follow the black curve, one must be careful not to acutely lower the BP because of the risk of further reducing CBF to an already ischemic vascular bed.
Accordingly, the American Heart/Stroke Association Guidelines for acute stroke therapy counsels against the lowering of blood pressure in patients who are not candidates for thrombolytic therapy unless:
the systolic pressure exceeds 220 or diastolic exceeds 120 mm Hg and then to lower BP only by 10 to 15% within the first 24 hours.
Neurologic signs and symptoms commonly caused by a stroke include:
the acute onset of weakness or paralysis in one limb or one side of the body,
decreased or lost sensation in one limb or one side of the body,
loss of vision in one eye (amaurosis fugax) or one visual field,
difficulty with language,
clumsiness or loss of balance, and difficulty with cognitive abilities.
Ischemic stroke may be categorized by blood vessel location or blood vessel size. What is an ‘Anterior circulation stroke’?
Stroke involving occlusion of the internal carotid, middle cerebral, anterior cerebral arteries or any of their branches.
What is a posterior circulation stroke defined as?
Posterior circulation strokes involve occlusion of the posterior cerebral, superior cerebellar, anterior inferior cerebellar, posterior inferior cerebellar, or vertebro-basilar arteries or any of their branches.
Large vessel strokes involve the large diameter cerebral blood vessels shown in the slide and small diameter strokes involve the long and short penetrating branches of the larger cerebral vessels.
This slide summarizes in pink the anterior circulation cerebral blood vessels that you should be familiar with and likewise in blue the posterior circulation blood vessels.
This slide depicts several functional brain areas supplied by the middle cerebral artery. Visualize the types of neurologic symptoms and signs that result from the occlusion of one of the MCA branches or occlusion of the entire MCA.
This slide presents a coronal section through the cerebral hemispheres once again showing functional neuroanatomy and the MCA supply to these areas. Note the small penetrating branches of the MCA called the lenticulostriate arteries. Once again envision the types of neurologic signs and symptoms that may result from occlusion of these branches.
This slide presents a midsagittal view of the right cerebral hemisphere and the blood supply provided by the anterior (grape) and posterior (blue) cerebral arteries.
This is a view of the base of the brain re-acquainting you with material we covered earlier. It shows the cerebral vessels comprising the Circle of Willis.
Recall the Circle of Willis functions to provide collateral blood flood in instances of proximal occlusions (closer to the heart) of cerebral blood vessels
This is an expanded view of the brainstem and cerebellum showing the blood supply to these structures.
There are several clinical brainstem stroke syndromes that I believe are useless for clinical decision making but unfortunately questions involving these syndromes have popped up on Board Exams. Thus I suggest you learn them at this time. To provide you with the needed stimulus, I also may ask a question about these syndromes on an Assessment exam. Your textbook (Krebs et al.) nicely summarizes these syndromes in three figures on pages 235 (lateral medullary syndrome), 236 (pontine syndrome), and 237 (midbrain syndrome). I will not elaborate on these here but have included these figures on the next three slides.
What causes Benedikt’s syndrome?
Infarcts at the midbrain level, more often than not, involve most of the small arteries originating from the tip of the basilar artery and from the P1 segments (PCA segment between the basilar and PCOM), resulting in a central midbrain infarct with bilateral upward extension to the thalami.
This is shown in an MRI diffusion weighted image
How does Benedikt’s syndrome classically present?
- ipsilateral CN III palsy and loss of pupillary contriction
- loss of discriminative touch on the contralateral side of the body due to a lesion of thed medial lemniscus
- contralateral tremor and ataxia due to a lesion of the red nucleus
How does pontine stroke syndrome present?
- gaze disorder due a lesion of the MLF
- loss of dsicriminative touch, vibration, and conscious proprioception on the contralateral side due to medial lemniscus lesion
contralateral hemiparesis due to corticospinal tract lesion
lesion of the pontine nuclei cause cerebellar lesions on both sides of the body
How does lateral medullary stroke syndrome (Wallenberg syndrome) present?
note that dysarthria and dysphagia via invovlement of the nucleus ambiguus or caudal NTS
It is clinically important that you be able to distinguish between the signs and symptoms of anterior versus posterior circulation strokes since these two vascular territories carry slightly different prognoses and treatment options. This slide describes the principle signs and symptoms of anterior circulation strokes. Describe them
For example, a right sided inferior quadrantanopsia will be caused by occlusion of the parietal-temporal branches of the left MCA.
This slide is from the Netter series and presents an man with possible signs/symptoms of an anterior circulation stroke. Describe it.
The upper figure depicts monocular visual loss of the right eye secondary to an embolus broken off from a clot in the internal carotid artery and traveling to and blocking the ophthalmic and central retinal arteries.
The lower figure depicts the same man with motor and sensory symptoms/signs on the left secondary to the occluded right internal carotid artery. Deficits of language or neglect will occur depending on which hemisphere is involved and which hemisphere is dominant for language in the patient.
How might a posterior circulation stroke present?
For example, a left posterior cerebral artery occlusion will cause homonymous hemianopsia of the right visual field. Review the material on the brainstem syndromes and clarify for yourself how the crossed-sign syndromes, e.g. weakness of the right face and left body are created in a patient.
This is a Netter series slide showing a man with signs/symptoms of a posterior circulation stroke.
The full figure of the man on the upper left depicts crossed extremity symptoms/signs (right arm and left leg) which while possible are very rarely, if ever, caused by a lesion above the foramen magnum. However, it is not uncommon to have crossed motor or sensory symptoms/signs involving the face ipsilateral to the lesion and the limbs contralateral to the same lesion.
The upper right figure depicts a Horner’s syndrome, the middle figures show a right homonymous hemianopsia, a man with vertigo/nausea/vomiting, a man with dysphagia, paralysis of a vocal cord, and loss of consciousness (coma).
Trivial Pursuit Point: The full figure of the man on the upper left is a curiosity since this presentation is extremely rare with only a handful of cases ever reported in the literature. Neuroanatomically there is one site above the foramen magnum where a single lesion could produce this picture.
This slide presents an coronal autopsy brain section (left) with arrows pointing to two of several lacunar infarcts. The figure on the right is a CT scan showing arrows pointing to bilateral thalamic lacunes.
This slide presents a simplified and diagrammatic depiction of the temporal development of atherothrombosis and the formation of atheroemboli.
Note the gradual buildup of the atheromatous plaque in the walls of the common carotid and bifurcation of the internal and external carotid arteries. The figure demonstrates the ulcerative process leading to platelet deposition and the formation of a red clot that may enlarge with time to totally occlude the vessel or fragment and send small platelet and/or thromboemboli downstream to distal cerebral blood vessels.
This slide presents serial sections through plaque in the carotid bifurcation and the histological appearance of a plaque stained with hematoxylin and eosin under a low power microscope.
This slide shows Netters depiction of a lacunar stroke in the pons (left middle figure), multiple basal ganglia and capsular lacunes (lower right figure), and the histological appearance of a small penetrating blood vessel occluded by the process of lipohyalinosis.
Lacunar infarcts may be caused by the same process that affects large cerebral vessels, i.e. atherothrombosis, but in this case the cause is microatheroma. They may also be caused by:
microemboli from more proximal blood vessels or the heart, but most commonly by a process called lipohyalinosis and fibrinoid necrosis. The two latter terms describe the histological transformation that occurs in the smooth muscle and intima of small penetrating cerebral vessels as a consequence of chronic hypertension.
This slide presents figures of most of the major causes of cardiogenic emboli that travel to brain. Since the brain receives 20% of cardiac output it is unfortunately a common target for embolic material released from the heart. The most common cause of cardiogenic emboli affecting the brain is:
atrial fibrillation (lower figure).
Valvular heart disease including mitral stenosis (top left), bacterial endocarditis (top right), and prosthetic heart valves (middle) may all be causes of cardioembolic stroke. Coronary artery disease with myocardial infarction and the formation of mural thrombi also are a source of cardiogenic emboli.
This slide shows a cardiogenic thrombus (blood clot) that has traveled from the heart to occlude the tip of the basilar artery. The figure on the right presents the histological appearance of such a thrombus in the basilar artery.
Inflammation of cerebral blood vessels producing CNS vasculitis may occur for a variety of reasons. Strokes from CNS vasculitis present differently than the usual garden variety ischemic strokes since multiple cerebral blood vessels may be involved instead of occlusion of a single blood vessel. The neurologic presentation reflects this multiple blood vessel involvement in that the patient develops multifocal signs.
The radiologic appearance of vasculitis on the cerebral arteriogram (CAG) is segmental narrowing and multiple occlusions of small blood vessels (arrows in the two radiographic pictures of CAG.)
Other causes of CNS vasculitis?
Well, not quite. We need to address a couple of queries Dr. Pulsinelli brought up. Recall the 26 year old woman who fell in the ice rink and developed left head and neck pain, difficulty speaking and right arm weakness. Hopefully you were able to recognize that the neurological deficit included a Broca’s expressive aphasia. With the right sided weakness, you should have identified the anterior branch of the middle cerebral artery as the vessel affected.
What was the pathophysiology?
The left neck pain radiating to the temple should have alerted you to “carotidynia” or pain involving the carotid artery. The left Horner syndrome supported carotid injury since the ascending sympathetic fibers from the superior cervical ganglion were affected by local injury. So, why would a young individual suffer a stroke from a carotid lesion? Carotid dissection. This can involve sudden twists and turns of the neck, trauma to the neck but carotid dissection can also occur spontaneously.
You may recall the unusual crossed motor deficit in the Netter figure on slide 31. Essentially, Netter dropped the ball on this one. He should have painted a crossed motor deficit involving the ipsilateral face and contralateral body. Producing a crossed limb deficit is pretty hard but can happen in an ipsilateral lesion of the pyramidal decussation. Recall that the arm fibers in the pyramidal decussation cross first (rostral) and then the leg fibers cross afterwards (caudal) so that a right rostral lesion of the decussation would catch the crossed fibers meant for the right arm and catch the uncrossed leg fibers heading for the left leg (just about to cross). That is an exceedingly rare phenomenon for stroke but might happen in head and neck trauma, if a fractured odontoid impaled one side of the pyramidal decussation.
