causes approx. 200,000 deaths in the US each year as well as considerable neurologic disability; 3rd leading killer in US
these diseases cause either ischemia-infarction (85-90%) or intracranial hemorrhage (10-15%)
morbidity and mortality from cerebrovascular diseases has been diminishing in recent years, due largely to better recognition and treatment of the underlying arterial and cardiac diseases, including hypertension
Co-morbidity of atherosclerotic disease: CAD, cerebrovascular disease, PAD
most cerebrovascular diseases present as the abrupt onset of a focal neurologic deficit
the deficit may remain fixed, or it may rapidly improve or progressively worsen
this abrupt onset of nonconvulsive and focal neurologic deficit is referred to as stroke or cerebrovascular accident (CVA)
Classification Of Cerebrovascular Diseases:
(1) Cerebral Ischemia-Infarction: Thrombotic occlusion and embolic occlusion (artery to artery and cardiogenic)
is caused by a reduction in blood flow that lasts for several seconds or a few minutes.
If the cessation of flow lasts for more than a few minutes, infarction of brain tissue results.
reduction in cerebral blood flow due to systemichypotension (e.g., cardiac arrhythmia, myocardial infarction, or hemorrhagic shock) usually produces syncope, infarction in the border zones between the major cerebral artery distributions, or widespread brain necrosis, depending on the duration of hypotension
ischemia or infarction, on the other hand, is usually caused by disease in the cerebral vessels themselves or by emboli from a proximal arterial source or the heart.
Thrombotic strokes occur without warning symptoms in 80-90%. 10-20% are heralded by one or more transient ischemic attacks (TIA’s). Thrombotic strokes often present with stuttering and fluctuating symptoms that worsen over several minutes or hours.
(2) Embolism (35%)
: can be cardiac source or atherothromboticarterial source
Embolic strokes usually present with a neurologic deficit that is maximum at onset
: Vasospasm and reversible cerebral vasoconstriction
: Dehydration, pericranial infection, postpartum and postoperative states, systemic cancer
(2) Intracranial Hemorrhage
: Intracerebral, Subarachnoid, Subdural (usually traumatic), and Epidural (traumatic)
and epidural hematomas are usually the result oftrauma, not cerebrovascular disease
the majority of intracerebral hemorrhages are associated with hypertension
hemorrhage (SAH) is usually due to a ruptured saccular aneurysm or, less commonly, an arteriovenous malformation
General Pathophysiology Of Cerebral Ischemia And Infarction:
within 10 sec after cerebral blood flow ceases: metabolic failure of brain tissue and EEG shows slowing of electrical activity
if the circulation is immediately restored Þ abrupt and complete recovery of function
if persists for a few minutes Þ neuronal injury
with restoration of flow, recovery of function takes several min/hr and may be incomplete. In addition, during the circulatory failure, the blood elements may sludge, the capillary endothelium may swell, and the blood flow may not reestablish itself, even when primary cause of the flow failure is corrected (the "no-reflow" phenomenon)
more prolonged periods of ischemia Þ frank tissue necrosis
Cerebral edema follows and progresses over the subsequent 2 to 4 days
if the region of infarction is large, edema may produce considerable mass effect with its attendant consequences
decreased CO Þ decreased cerebral blood flow Þ ischemic (border zone areas most vulnerable – watershed areas)
of cerebral ischemia and infarction are atherosclerosiswith thromboembolism and cardiogenicembolism
Atherosclerotic Ischemia and Infarction
is maximal at arterial bifurcations, and it commonly affects the origin of the internal carotid artery in the neck and the origin of major and minor arterial branches inside the head
atherosclerotic plaques can cause an arterial stenosis that produces a hemodynamic obstruction to flow. If this regional ß in cerebral blood flow falls below a critical level, it will cause a transient or permanent ischemic event.
– important cause of retinal and hemispheric ischemia and infarction. When an atherosclerotic plaque on the arterial wall ulcerates, the necrotic material may dislodge and serve as emboli or may provide a surface on which aggregation of platelets and coagulation of fibrin occurs. The resulting fibrin clot also may dislodge into the arterial circulation, or it may enlarge and produce thrombotic occlusion of the artery
are small infarcts in the deep white matter of the hemisphere or brainstem. Due to HTN-induced lipohyalinosis or arteriosclerosis of small penetrating arteries
although the exact cause of ischemia or infarction in a given patient with atherosclerosis is not always known, the primary abnormality is clearly atherosclerosis with its complicating lesion, the fibrous plaque. The plaque may result in stenosis or ulceration, with subsequent thrombosis or embolization
Clinical Manifestations Of Ischemic Stroke
typical ischemic stroke presents with the abrupt onset of a focal neurologic deficit
A TIA is manifested by a neurologic deficit lasting < 24 h (usually 5 to 20 min). It is often referred to as a mini-, warning, or transient stroke, because it quickly resolves but often portends an impending stroke. The deficit is focal and confined to an area of the brain perfused by a specific artery.
for TIA’s are:
low flow in an artery due to tight stenosis or occlusion
embolism from heart, proximal arterial/atherosclerotic plaque debris, thrombus
any obstructive vascular process in extra- or intracranial arteries can cause low-flow TIA if collateral flow to potentially ischemic brain is also impaired, and can lead to arterial thrombosis; if symptoms persist >24hrs, infarction has occurred
TIA’s are highly predictable for stroke – risk of stroke is 33% within 5 yrs of last TIA; also age and frequency of TIA’s increase risk (>5 TIA’s in 2 wks Þ 20% have stroke in 3 months, and 30% in 6 months)
Internal Carotid Artery Disease
Þ attacks of transient monocular blindness; TIA’s; frequent unaccustomed headaches; associated history of CAD or PVD; neck bruits, retinal infarcts or cholesterol plaques
ACA (anterior cerebral artery) stroke
: contralateral hemiplagia
Posterior circulation (large vessel disease)
: cranial nerve dysfunction; cerebellar involvement; Horner syndrome; ANS nuclei and tracts; abnormal respiratory control; altered LOC; corticospinal, spinothalamic involvement
Reversible ischemic neurologic deficit (RIND)
is an infrequently used term that defines an ischemic event in which the deficit usually recovers over a 24- to 72-h period, but which may take as long as 1 week to resolve
(cerebral infarction) of the thrombotic type is generally nonhemorrhagic. It typically evolves to its maximal deficit within a few hours. Often, patient awakens with a completed deficit. A completed stroke is sometimes heralded by one or more TIA’s in preceding days/weeks/months, most likely when tight arterial stenosis is causative.
In progressing stroke, or stroke-in-evolution, the focal ischemia worsens from min to min or hr to hr. There are usually stepwise incremental increases in neurologic deficit occurring over a several-hour period. While there may be several pathogenic mechanisms producing a progressing stroke, one such mechanism appears to be a thrombus-in-evolution, with a thrombus extending from its site of origin in a primary artery and progressively obliterating collateral branches, thereby interfering with anastomotic vessels.
the hallmark presentation is the abrupt onset of a hemiparesis in an individual in the atherosclerotic age group.
refers to infarction following atherothrombotic or lipohyalinotic occlusion of one of the penetrating branches of the circle of Willis, middle cerebral artery stem, or vertebral and basilar arteries.
deficit evolves gradually with frequent fluctuations and progression
the middle cerebral artery stem, the arteries comprising the circle of Willis, and basilar and vertebral arteries all give rise
to 100- to 300-
m m diameter branches that penetrate the deep gray and white matter of the cerebrum or brainstem
each of these small branches can thrombose either by atherothrombotic disease at its origin or by the development of lipohyalinotic thickening. Thrombosis of these vessels causes small infarcts that are referred to as lacunes
HTN (also DM) is principal risk factor for such small-vessel disease. Lacunar infarcts cause ~20% of all strokes.
Penetrating and branch artery disease
Þ subintimal foam cells and deposition of fibrinoid material within vessel walls, therefore NO penumbrum (no collateral flow); whorles, tangles of connective tissue
Þ pure motor hemiparesis, dysarthria-clumsy hand, pure sensory deficit (thalamic syndrome), and sensory-motor strokes
Laboratory And Imaging Evaluation
accurate diagnosis is based largely on the history and examination, supplemented by judicious use of blood tests and imaging of the brain [CT and MR imaging (MRI)] and its blood vessels (arterial Doppler ultrasonography, MRA (magnetic resonance angiogram) and x-ray angiography, and invasive angiogram (gold standard))
electrocardiogram (ECG) may demonstrate conduction abnormalities and arrhythmias or reveal evidence of recent MI
will often demonstrate an area of infarction and will confirm or exclude the presence of an intracerebral, subdural, or epidural hemorrhage or other mass lesion. Moreover, it may demonstrate large aneurysms and AVM’s and subarachnoid or intraventricular blood.
A lumbar puncture (LP) will confirm or exclude subarachnoid hemorrhage or meningitis due to syphilis or other chronic infections. An LP should not be performed on patients with intracranial mass lesions
is the most sensitive method to detect embolic infarction
Ex: large MCA infarct
Þ 1st step is CT Þ 2nd MRI of brain Þ 3rd diffusion weighted MRI (shows abnormal perfusion)
Treatment and Prevention
of the atherosclerosis factors, hypertension is of the greatest importance. In general, all HTN should be treated.
prevent atherothrombotic events, including TIA and stroke. They inhibit the formationof intraarterial platelet aggregates that can form on diseased arteries, induce thrombus formation, and occlude the artery or embolize into the distal circulation. Aspirin and ticlopidine are used most.
– Its antiplatelet effect is accomplished by acetylating the cyclooxygenase enzyme in platelets. This irreversibly inhibits the formation in platelets of thromboxane A2, a platelet aggregating and vasoconstricting prostaglandin. Aspirin also inhibits the formation in endothelial cells of prostacyclin, an antiaggregating and vasodilating prostaglandin.
(and clopidogrel bisulfate) – blocks the ADP receptor on platelets and thus prevents the cascade resulting in activation of the glycoprotein IIb/IIIa receptor that leads to fibrinogen binding to the platelet and consequent platelet aggregation. Ticlopidine is more effective than aspirin. Side effects: neutropenia, diarrhea, and skin rash
is an antiplatelet agent that acts by inhibiting platelet phosphodiesterase, which is responsible for the breakdown of cyclic AMP. The resulting elevation in cyclic AMP inhibits aggregation of platelets
(2) Anticoagulation therapy:
(ie nadroparin) is widely used for "unstable TIA " (i.e., crescendo or recent-onset TIA)
if long-term anticoagulation is chosen, warfarin is administered.
surgery for atherosclerotic occlusive disease is largely limited to carotid endarterectomy for plaques located at the origin of the internal carotid artery in the neck; clamp off arteries
Þ make incision Þ clean out plaque Þ stitch up
surgery in the proximal common carotid, the subclavian, and the vertebral arteries is uncommon.
anastomosing extracranial scalp arteries to major intracranial arteries to bypass inoperable obstructions in the internal carotid artery is of no value.
Stenosis < 50%
Þ antiplatelet therapy; no benefit with surgery
Þusually surgical benefit; individualize to patient
Þ surgery benefits
Asymptomatic patients and stenosis > 60%
Þ carotid endarterectomy provides absolute risk reduction of 5.8% over 5 yrs; relative risk reduction of 55% (decrease risk from 2% to 1% so not as overwhelming as it looks); no effect shown in women, only helpful for men
Þ minimally invasive surgery Þ carotid artery stenting; no more effective than surgery
(HTN, hemodilution, hypervolemia) Þ present with vasospasms, thus Ý BP and flow to areas of brain
Treatment (Acute management)
when cerebral infarction occurs, the immediate goal is to optimize cerebral perfusion of the ischemic area
– lyse the clot
give if within 3 hrs of deficit; IV administer if within 6 hrs – anti-coagulant
do not give to patients with hemorrhage or people with signs of infarct on CT
Þ may increase chance of hemorrhage
cerebral infarcts may be pale (nonhemorrhagic) or red (hemorrhagic).
of varying degree is common in all infarcts, but extravasation of blood is usually associated with embolic infarcts.
because emboli migrate and lyse, recirculation into the infarcted brain may cause petechial hemorrhages.
sometimes there is enough seepage of blood into the infarct to cause visible hemorrhagic infarction on a CT scan.
infarcts in the distribution of small, penetrating arteries leave small cavities or lacunes (lacunar infarcts), whereas major arterial occlusions produce a wide area of necrosis that leaves a large, fluid-filled cavity in the brain.
invariably accompanies the tissue necrosis. In small infarcts it may be relatively insignificant. In large infarcts, however, massive edema compresses adjacent tissue and adds to the ischemic process; it also increases intracranialpressure and may cause herniation of the brain from one intracranial compartment to another.
most common type of nontraumatic intracranial hemorrhage. Important cause of stroke, esp. in Asians and blacks.
and cerebral amyloid angiopathy cause the majority of these hemorrhages. Minor causes Þ tumors and vascular malformations
advanced age and heavy alcohol consumption increase the risk. Cocaine-induced hemorrhage is one of the most important causes in the young.
Bleeding with brain tumors; Systemic bleeding disorders, including anticoagulation therapy; Hemorrhagic infarction
Pathophysiology And Pathology
intracerebral hemorrhage usually results from spontaneous rupture of a small penetrating artery deep in the brain.
the most common sites are:
(1) the basal ganglia (putamen, thalamus, and adjacent deep white matter)
(2) the deep cerebellum
(3) the pons
the small arteries in these areas seem most prone to hypertension-induced vascular injury
the leak may be small, or a large clot may form and compress adjacent tissue, causing herniation and death
rupture or seepage into the ventricular system often occurs; primary intraventricular hemorrhage is rare
if the patient survives, the clot liquefies, is absorbed, and leaves only a small residual cleft
most hypertensive intracerebral hemorrhages develop over 30 to 90 min, whereas those associated with anticoagulant therapy may evolve for as long as 24 to 48 h. Once bleeding stops, it generally does not start again. Within 48 h macrophages begin to phagocytize the hemorrhage at its outer surface. After 1 to 6 months, the hemorrhage is generally resolved.
Morbidity – 88% disability; 33% mortality
Þ very deadly disease
is the leading cause of primary cerebral hemorrhage. Prevention is primarily aimed at reducing hypertension, excessive alcohol use, and use of illicit drugs such as cocaine and amphetamines.
Treatment (Acute Management
) – ~75% with a hypertensive intracerebral hemorrhage die. Size/location of the hematoma determines prognosis.
surgical evacuation of hematoma in certain instances
Þ indications for surgery are uncertain!
(osmotic agent) ß intracranial pressure that has been raised by the volume of the hematoma and edema
the commonest cause of spontaneous SAH is a ruptured saccular aneurysm; can occur any time after adulthood
other causes – bleeding from an AVM or extension into the subarachnoid space from a primary intracerebral hemorrhage
Pathophysiology And Pathology
occur at the bifurcations of the large arteries at the base of brain and rupture into subarachnoid space in the basal cisterns
~85% of aneurysms occur on the anteriorcirculation (15% in posterior circulation), mostly on the circle of Willis.
Aneurysms can undergo small ruptures and leaks of blood into the subarachnoid space, so-called warning leaks
Sudden unexplained headache at any location should raise suspicion of SAH
At the moment of aneurysmal rupture with major SAH, the intracranial pressure suddenly rises. Abrupt, severe, and generalized vasospasm may occur transiently. These events may account for the sudden transient loss of consciousness that occurs in nearly half of patients
Þ the hemorrhage is not the problem, the increased intracranial pressure is!! (if it continues to increase, on perfusion to brain)
the headache (usually generalized) is often called by the patient "the worst headache of my life."
is common and when coupled with sudden headache should always raise the suspicion of SAH.
– differentiating from SAH
: sudden onset; no history of headaches – most likely to be SAH
: bilateral pain; contraction of neck or pericranial muscles; no neurologic events
: history of headache; gradual onset; visual disturbance; nausea; throbbing quality
: unilateral pain; no visual/cerebral symptoms; facial erythema; rhinorrhea; brief
Laboratory And Imaging Evaluation
(The hallmark of aneurysmal rupture is blood in CSF)
confirms 95% of SAH’s – if scan negative, or headache for > 4 days; lumbar puncture indicated
the extent and location of subarachnoid blood on CT scan help locate the underlying aneurysm and identify the cause of any neurologic deficit. The clot also will help predict delayed vasospasm.
A noncontrast CT scan should be done first, because on an enhanced scan normal arteries in the basal cisterns may be mistaken for clotted blood.
prior to scanning is indicated only if a CT scan is not available at the time of the suspected SAH.
Once the diagnosis of hemorrhage from ruptured saccular aneurysm has been established, four-vesselangiography (both carotids and vertebrals) is generally performed to localize and define the anatomic details of the aneurysm and to determine if other unruptured aneurysms exist.
: endovascular surgery (put platinium coils into the aneurysm); gamma knife surgery
, or angiomas, may be tiny and cryptic or massive anomalies that cause headaches, brain damage, seizures, and hemorrhages
AVM’s are the most important vascular malformations of the nervous system and consist of a tangle of abnormal vessels forming an abnormal communication between the arterial and venous systems
Most are developmental arteriovenous fistulas in which the involved vessels enlarge with the passage of time.
AVM’s vary in size from a small blemish a few millimeters in diameter to a huge mass of tortuous channels.
Hypertrophic and dilated arterial feeders approach the main lesion, disappear below the cortex, and break up into a network of thin-walled blood vessels that connect directly with draining veins. These often form huge, dilated, pulsating channels carrying away arterial blood.
the blood vessels forming the tangle interposed between arteries and veins are usually abnormally thin.
AVM’s occur in all parts of the brain, brainstem, and spinal cord, but the largest ones are most frequently in the posterior half of the hemispheres; AVM’s are more frequent in men
the chief clinical symptoms and signs are headache, seizures, and those associated with rupture.
AVM’s less than 0.5 cm in diameter are usually low-pressure venous angiomas that bleed infrequently and minimally
If they bleed, surgical or gamma-knife resection or obliteration should be considered.