Stroke

CVS-1
Definition:
• According to WHO, Stroke is defined as an accident to the brain with
“rapidly developing clinical signs of focal or global disturbance to cerebral
function, with symptoms lasting 24 hours or longer, or leading to death,
with no apparent cause other than of vascular origin and includes cerebral
infarction, intracerebral hemorrhage, and subarachnoid hemorrhage”
• Acute stroke is also commonly called a cerebrovascular accident which is
not a term preferred by most stroke neurologists
• Stroke is NOT an accident
• The better and more meaningful term is “brain attack”
“, similar. In
significance to “heart attack””
Types of strokes:
A. Ischemic stroke:
• caused by interruption of blood flow to a certain area of the brain.
Ischemic stroke
• Accounts for 85% of all acute strokes
• According to the TOAST classification (a system used in the field of stroke
medicine to categorize acute ischemic strokes based on their etiology). There
are five main types of ischemic strokes
1. large vessel atherosclerosis
2. small vessel diseases (lacunar infarcts)
3. cardioembolic strokes
4. stroke of other determined etiology
5. cryptogenic strokes/stroke of undetermined etiology
Cont’d
B. Hemorrhagic strokes
• 15% of acute strokes; caused by bursting of a blood vessel i.e. acute
hemorrhage
• two main types of hemorrhagic strokes,
1. Intracerebral hemorrhage (ICH): bleeding into the brain tissue
2. Subarachnoid hemorrhage:
• bleeding in the space between your brain and the membrane that
covers it (subarachnoid space)
• occurs when a weak area in a blood vessel (aneürysm) on the surface
of the brain bursts and leaks which
• accounts for about 5% of all strokes
Brain hemorrhage:
Etiology/ Risk factors:
• Hypertension, diabetes mellitus, hypercholesterolemia, physical
inactivity, obesity, genetics, and smoking.
• Cerebral emboli commonly originate from the heart, especially in
patients with preexisting heart arrhythmias (atrial fibrillation),
valvular disease, structural defects (atrial and ventricular septal
defects) and chronic rheumatic heart disease.
• Emboli may lodge in areas of preexisting stenosis.
• Alcohol intake has a J-shaped relationship with ischemic stroke.
Mild to moderate drinking carries a slightly lower risk of ischemic
stroke yet heavier drinking increases the risk drastically. Alcohol
intake increases the risk of hemorrhagic stroke in a near-linear
relationship.
Pathophysiology:(ischemic stroke)
• In carotid atherosclerosis progressive accumulation of lipids and inflammatory
cells in the intima of the affected arteries, combined with hypertrophy of arterial
smooth muscle cells, results in plaque formation.
- Sheer stress may result in plaque rupture, collagen exposure, platelet
aggregation, and clot formation
• Clot may remain in the vessel, causing local occlusion, or travel distally as an
embolism, eventually lodging downstream in a cerebral vessel
• In the case of cardiogenic embolism,
, stasis of blood in the atria or ventricles of
the heart leads to the formation of local clots that can become dislodged and
travel directly through the aorta to the cerebral circulation
- Final result of both thrombus formation and erfoolism is an arterial occlusion,
decreasing cerebral blood flow and causing ischemia distal to the occlusion
Cont’d
• Normal cerebral blood flow averages 50 mL/100 g per minute, and this is
maintained over a wide range of blood pressures (mean arterial pressures of
50 to 150 mm Hg) by a process called cerebral autoregulation
• Cerebral blood vessels dilate and constrict in response to changes in blood
pressure, but this process can be impaired by atherosclerosis and acute injury,
such as stroke
• When local cerebral blood flow decreases below 20 mL/100 g per minute
ischemia ensues, and when further reductions below 12 ml/100 g per minute
persist, irreversible damage to the brain occurs, and this is called infarction
• Tissue that is ischemic but maintains membrane integrity is referred to as
the ischemic penumbra because it usually surrounds the infarct core. This
penumbra is potentially salvageable through therapeutic intervention.
Cont’d
• Reduction in the provision of nutrients to the ischemic cell eventually leads to
depletion of the high-energy phosphates (e.g-, ATP) necessary for the maintenance
of membrane integrity
• Subsequently, extracellular potassium accumulates at the same time that sodium
and water are sequestered intracellularly, leading to cell swelling and eventual lysis.
• Electrolyte imbalance also leads to depolarization of the cell and influx of calcium
into the cell. The increase in intracellular calcium results in the activation of lipases,
proteases, and endonucleases and the release of free fatty acids from membrane
phospholipids
• Depolarization of the neuron leads to the release of excitatory amino acids, such
as glutamate and aspartate, that perpetuate the neuronal damage when released in
excess
• Accumulation of free fatty acids, including arachidonic acid, results in the
formation of prostaglandins, leukotrienes, and free radicals
Cont'd
• In ischemia, the magnitude of free radical production
overwhelms normal scavenging systems, leaving these
reactive molecules to attack cell membranes and contribute to
the mounting intracellular acidosis
• All these events occur within 2 to 3 hours of the onset of
ischemia and contribute to the ultimate cell death
• Influx of activated inflammatory cells, starting from 2 hours
after the onset of ischemia and lasting for several days.
• Also, the initiation of apoptosis, or programmed cell death, is
thought to occur many hours after the acute insult and may
interfere with recovery and repair of brain tissue.
Pathophysiology (hemorrhage
stroke)
• Presence of blood in the brain parenchyma causes damage to
the surrounding tissue through the mechanical effect it
produces (mass effect) and the neurotoxicity of the blood
components and their degradation products.
• Compression of the tissue surrounding the hematoma also
may lead to secondary ischemia in some cases.
• Approx. 30% of intracerebral hemorrhages continue to
enlarge over the first 24 hours
• Much of the early mortality of hemorrhagic stroke (up to 50%
at 30 days) is due to the abrupt increase in intracranial
pressure that can lead to herniation and death
Non pharmacological therapy:
A. ISCHEMIC STROKE
• Craniectomy: to release some of the rising pressure
• Surgical decompression: can be lifesaving in patients with
significant swelling associated with a cerebellar infarction,
• Early rehabilitation: shown to be very effective in reducing the
ultimate disability owing to ischemic stroke In secondary
prevention:
• Carotid endarterectomy: of an ulcerated and/or stenotic carotid
artery is a very effective way to reduce stroke incidence and
recurrence in appropriate patients
• Carotid stenting
Cont'd
B. HEMORRHAGIC STROKE
• Surgical intervention: to either clip or ablate
(remove) the offending vascular abnormality
substantially reduces mortality owing to re-
bleeding.
• Insertion of an extraventricular drain (EVD) and
subsequent monitoring of intracranial pressure are done
commonly and are the least invasive of the procedures
• Surgical decompression: last option in a life-threatening
situation.
Pharmacological therapy:
A. ISCHEMIC STROKE
Drug Treatments of First Choice: Published
Guidelines
Only two pharmacologic agents recommended with
a grade A recommendation:
1. Intravenous tissue plasminogen activator (tPA)
(Alteplase,
Reteplase, and Tenecteplase) within 3 hours of onset
2. Aspirin within 48 hours of onset.
Cont’d

• Early reperfusion (<3 hours from onset) with intravenous tPA reduce ultimate
disability due to ischemic stroke
• Caution & adherence to a strict protocol is essential to achieving positive
outcomes
• Essentials of the treatment protocol can be summarized as:
(1) stroke team activation,
(2) onset of symptoms within 3 hours
(3) CT scan to rule out hemorrhage
(4) Meet inclusion and exclusion criteria
(5) Administer PA 0.9 mg/ kg over 1 hour, with 10% given as initial bolus over 1
minute
(6) Avoid antithrombotic (anticoagulant or antiplatelet) therapy for 24 hours
(7) Monitor the patient closely for response and hemorrhage.
Cont’d
B. HEMORRHAGIC STROKE
• Currently no proven pharmacologic strategies for treating intracerebra
nemorrhage (ICH)
• Subarachnoid hemorrhage (SAH) owing to aneurysm rupture is associated with a
high incidence of delayed cerebral ischemia (DCI) in the 2 weeks following the
bleeding episode- Vasospasm of the cerebral vasculature
• Calcium channel blocker Nimodipine is recommended to reduce the incidence and
severity of neurologic deficits owing to DCI
• Nimodipine at a dose of 60 mg every 4 hours should be initiated on diagnosis and
continued for 21 days in all SAH patients
• Nimodipine therapy complicated due to high incidence of hypotension
• Can be managed by reducing the dosing interval to 30 mg every 2 hours (same
,, reducing the total daily dose (30 mg every 4 hours), and maintaining
intravascular volume and vasopressor therapy