4 - Cerebrovascular Disease and Drug Use

Cerebrovascular disease ภาษาไทย

โรคหลอดเลือดสมอง

Cerebrovascular disease meaning

A group of diseases that cause ischemia/bleeding of the brain with one or more of the cerebral blood vessels being involved in the process

Stroke definition

A type of cerebrovascular disease: A neurological deficit due to an acute, focal CNS injury from infarction or hemorrhage

• Ischemic: ตีบ ตัน

• Hemorrhagic: แตก

How does __ affect stroke:

• Age

• Gender

• Race

• Incidence doubles every decade over 55

• Males get strokes more often, strokes are more lethal in females

• Caucasians get strokes less

Modifiable risk factors of stroke:

1. Atherosclerosis: Hypertension, smoking, DM, etc.

2. Cardioemoblic: A-fib, CHF,MI, IE

3. Hypercoagulability: Oral contraceptive pills, estrogen therapy

Ischemic stroke

• Definition

• Main types

• An episode of neurologic dysfunction caused by focal CNS infarction

• Large artery atherosclerosis, cardioembolism, small vessel occlusion, stroke of other determined etiology(think aortic dissection), stroke of undetermined etiology

What happens at the cellular level in an ischemic stroke?

No blood supply → energy runs out → Na+K+ATPase stops → Na+ builds up in the cell so cytotoxic edema happens, and depolarization also triggers Ca2+ release → glutamate released and can’t be cleared due to no Na+ gradient as energy source → Excitotoxicity

What are the savable and non-savable zones of an ischemic stroke?

• Unsavable → ischemic core

• Savable → ischemic penumbra due to collateral blood flow

Tissue change after ischemic stroke

• 12-24hrs: Red/pyknotic neuron

• 24-48hrs: Neutrophils

• 48hrs-2wks: Macrophage, reactive gliosis

• 2wks-months: Repair leaving a fluid-filled cavity + rim of gliosis

What kind of ischemic stroke causes a lacunar infarct?

Small artery occlusion

What is this condition, and how does it happen?

Ischemic stroke with hemorrhagic transformation

• An already infarcted already begins to bleed because when the clot is dissolved, blood flow returns, but the ischemic vessels are leaky, so blood leaks into the dead tissue

Most common site of ischemic stroke

Middle cerebral artery

Key signs of MCA, ACA, PCA, brainstem being affected

• MCA: Weakness/numbness of contralat. face/arm

• ACA: Weakness/numbness of contralat. leg

• PCA: Loss of opposite half of visual field in both eyes

• Brainstem: Vertigo, coordination, face symptoms on one side, body symptoms on the other

Transient Ischemic Attack(TIA)

• Definition

• Risk

• An episode of neurologic dysfunction caused by focal CNS ischemia w/o infarction detected

• An actual ischemic stroke, often w/in first 2 days of the TIA

How long is an episode of a transient ischemic attack?

• Often less than an hour

Hemorrhagic stroke

• Traumatic or non-traumatic

• Types + Frequency

• Non-traumatic

• Intracerebral(75%), subarachnoid(25%)

Main cause of intracerebral hemorrhagic stroke

Hypertension

ICP @ presentation in intracerebral hemorrhage vs ischemic stroke

• Intracerebral hemorrhage comes w increased ICP due to the blood spilling out

• Ischemic stroke: Normal so far, will only increase if edema occurs in days 2-5

What is this condition, and what does it tell us?

Slit hemorrhage, a small cavity with a brown rim(from hemosidern) tells us of a ruptured penetrating artery that has healed

In a patient with chronic hypertension, what happens to their autoregulation range?

It shifts to the right, aka it’s used to maintaining cerebral blood flow in a higher range of BP, so the normal 50-150mmHg range might actually not be valid for them

Where does blood go in an intracerebral hemorrhage vs subarachnoid hemorrhage?

• Into brain tissue vs subarachnoid space

Subarachnoid hemorrhage main cause

• Ruptured saccular(berry aneurysm)

What is a berry aneurysm, and where is the most common location?

A small outpouching of an artery, found @ bifurcations of the Circle of Willis, with the most common locations being in the anterior part like the ACA.

Berry aneurysm

• Symptoms

• Risk factors

• None, but when it ruptures…

  • Thunderclap headache

  • Neck stiffness

  • Vasospasms(Delayed narrowing of cerebral arteries after SAH around 3 days after because the blood surrounding the arteries is an irritant → delayed cerebral ischemia)

  • Hydrocephalus(Can be obstructive from clots, or communicating from blockage of arachnoid granulations or fibrosis later)

• Hypertension, smoking, family history and connective tissue/vascular disorders

Global cerebral ischemia

• What is it

• Cause

• Reduced blood flow to the whole brain

• Not cerebrovascular, like cardiac arrest or sepsis

Selective vulnerability

• Not all brain cells and regions are equally sensitive to ischemia

  • Neurons die before glia

  • Certain regions of neurons die faster(Hippocampus, purkinje cells of cerebellum, etc.)

Border zone infarct

• Other name

• What is it?

• Watershed infarct

• Border between supply area of 2 major cerebral arteries, often receiving the least flow; most common one is the ACA MCA border zone → “Man in a barrel” pattern

BE-FAST

• Stroke warning signs and action

  • B: Balance

  • E: Eyes

  • F: Face drooping

  • A: Arm weakness

  • S: Speech slurred

  • T: Call 1669

What is the best way to differentiate between ischemic and hemorrhagic stroke, and how?

Non-contrast CT Brain

• Ischemic stroke: Often looks normal, then the infarcted area slowly turns dark

• Hemorrhagic stroke: Appears as a bright white area

When would an acute ischemic stroke patient receive fibrinolytics?

• Yes fibrinolytics: No bleeding/early ischemic CT signs only, w/in 4.5 hours of last known well, BP under 185/110, over 18

• No fibrinolytics: Over 4.5 hrs from last known well, high bleeding risk(like a past hx of brain bleed), BP over 185/110, presence of brain tumor

Why is 4.5. hrs so important in deciding if we should give fibrinolytics?

Because before 4.5 hrs likely means that the penumbra is still large, the ischemic core is probably smaller, so we can save more brain tissue, and within 4.5 hrs, the bleeding risk isn’t that high yet because vessels in the ischemic area aren’t that damaged yet

How do we treat hypertension in acute ischemic stroke patients who aren’t on fibrinolytics?

• BP above 220/120(Or below, but with a condition where high BP is dangerous like CHF, dissection, MI) → BP is dangerous, use IV nicardipine, IV labetalol, oral captopril(backup)

• BP 220/120 or below → No need to treat, since we don’t want to reduce blood flow to the penumbra

Main fibrinolytics in the brain and their differences

Alteplase vs tenecteplase

• Tenecteplase lasts longer and is more selective

What do anti-platelets and anti-coagulants do in acute ischemic stroke?

• Reducing reoccurrence of more clots

  • Anti-platelets: Non-cardioembolic strokes

  • Anti-coagulants: Cardio-embolic strokes

What type of occlusion may need a mechanical thromboectomy, and would it be done before or after fibrinolytics?

• Large vessel occlusion, done AFTER fibrinolytics

Blood pressure target in an intracerebral hemorrhage

Around 140, but not below 130. This is so that blood doesn’t get pushed out into the hematoma more than it already is, but also because we don’t want to cause ischemia

Drugs used in intracerebral hemorrhage to lower BP

IV nicardipine and labetalol

What does mannitol treat in a hemorrhagic stroke?

The increased ICP

Drug used in aneurysmal subarachnoid hemorrhage, and why this one?

Nimodipine → Proven to reduce delayed cerebral ischemia(reduces vasospasm)