Cerebrovascular Disease

Week 7 Newell

Cerebral Ischemia
Neurons must have oxygen to live Total loss of oxygen > 5-6 minutes = irreversible cell changes Other CNS cells may tolerate the same stress Selective Vulnerability of Neurons

Hypoxic Ischemic Injury Patterns

1. Global Ischemia (entire brain is affected, like heart stops, shock, hypotension) 2. Focal Ischemia

Global Ischemia
Selective Vulnerability
Some neurons are more susceptible than others Note that there are differences in susceptibility between adults and infants Infants diencephalon is much more susceptible than adults o CA1 of Hippocampal Formation (both adults and infants) o Purkinje cells of Cerebellum o Pyramidal neurons: III, V, VI of Cerebral Cortex Sustained shock/ low blood pressure First to suffer with global ischemia o ACA/MCA endzone o Hypotension can play a role in this

Watershed (Borderzone) Infarcts

Case #1: Acute Global Ischemia

A 47 year-old man is found pulseless in a parking lot. A passerby performs CPR until paramedics arrive. A pulse is returned within 8-9 minutes of the witnessed collapse. After 24 hours of hospitalization, he has a fatal dysrhythmia and dies.

Timeline = Acute Within 12-24 hours

Red neurons (hypoxia, ischemic injury) loss of Nissl, Lost nucleolus Microvacuolization (bubbly lookcells/ BV leaking) Nuclear pyknosis CA1 of HF, Purkinje cells, pyramidal neurons

Case #2: Subacute Global Ischemia

A 47 year-old man is found pulseless in a parking lot. A passerby performs CPR until paramedics arrive. A pulse is returned within 8-9 minutes of the witnessed collapse. After 5 days of hospitalization, he has a fatal dysrhythmia and dies.

Timeline = Subacute 24 hours to 2 weeks

Necrosis Macrophages (clean up dead and dying neurons) within 48hr Vascular proliferation: like granulation tissue healing in skin Gliosis (astrocytosis, proliferation of astrocytes)

Focal Ischemia (Infarcts)

o o o o Thrombosis: occluded BV at the site of the injury Embolism: traveling blood clot that began somewhere else Vasculitis: inflammatory BV disease CADASIL: Cerebral AD Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Infarcts: Thombosis
In situ blood clot (blood clot at site of injury) Majority: atherosclerosis Common site: o Carotid Bifurcation o Middle Cerebral Artery origin o Top/bottom of the Basilar Artery (Posterior circulation)

Case #3: Acute Infarct

A 68 year-old man awakens with left sided weakness and speech difficulties. A head CT scan reveals an area of signal change in the right frontotemporal lobes. He dies 5 days later. See demarcation, swelling, shifting, blood at site

Case #4: Old Infarct

A 66 year old woman awakens with left sided weakness. A head CT scan reveals an area of signal change in the right frontal cortex. She recovers and dies 1 year after infarct. Note the remodeling that has taken place. As the tissue was taken away, a cystic cavity was left. The meningothelial cells that are covering the brain are resistant to all this infarct and they will tend to stay intact. White matter and cortex will discolor and atrophy.

CADASIL: Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

o Hereditary Vascular Dementia o Notch3 gene mutation (Chromosome 19) Affects mainly the arterioles and leads to infarcts deeper in the brain (white matter) and will cause chronic damage/ischemia to the white matter (leukoencephalopathy) may mimic MS!! Features of CADASIL: 1. Migraine with aura (20-30 year olds) 2. Psychiatric illness: depression 3. Recurrent infarcts: TIAs or completed infarcts 4. Cognitive decline, often dementia (>80% of those 65+) Periventricular white matter change White matter change also seen at the temporal poles See reduction of myelin in white matter Changes in blood vessel stainingdeposits are characteristic (seen thru body) Granular deposits that may be related to Notch3

Hypertensive CV Disease
Arteriolar Sclerosis Deep nuclei, white matter, and brainstem Lacunes (15 mm or <) Putamen, globus pallidus Thalamus Internal capsule Deep white matter Caudate nucleus Pons Multiple infarcts in deep nuclei but without granular deposits (CADASIL), smaller vessel disease

Intracranial Hemorrhage Overview

Sites: intraparenchymal, subarachnoid, epidural, subdural

Intraparenchymal Hemorrhage
Most common cause: hypertension Pathogenesis: o Accelerated atherosclerosis o Hyaline arteriolosclerosisincreased fragility o Charcot Bouchard aneurysms (debated)

Hypertensive Hemorrhage Sites

1. 2. 3. 4. Putamen Thalamus Pons Cerebellum Hemorrhage shows LOTS of blood, unlike ischemia.

Cerebral Amyloid Angiopathy

Abnormal material in the blood vessel wall Amyloid material BV are not all equal in which ones acquire this material small vessels are more likely to acquire it. Small vessels in the subarachnoid space Small vessels in the cortex

Not a process that affects white matter blood vessels When they break open, bleeding occurs, and the blood goes deeper into the brainLobar Hemorrhage Blood vessel disease that is associated with aging Same amyloid as seen with Alzheimers disease Hereditary forms

Arteriovenous Malformation:
Can occur in the brain Arterial blood shunting to the venous blood because there are no capillaries. High pressure into the veins Intra-parechymal hemorrhage

Cavernous Angioma
Back to back blood vessels No intervening brain found Can also bleed Benign but give rise to bleeding Intra-parenchymal hemorrhage

Case #4: Subarachnoid Hemorrhage

A 48 year-old woman with 3 hours of a severe headache (the worst in my life) collapses and dies within an hour. An autopsy is performed.

Subarachnoid Hemorrhage
Berry aneurysm occur in Circle of Willis BV (mostly Anterior Circulation) Increased in certain disorders AD polycystic kidney disease NF1 Marfan syndrome Ehlers-Danlos IV Risk factors: Smoking, hypertension

Berry Aneurysms are typically acquired Weakened area in the blood vessel wall and microscopically, usually devoid of elastic tissue and smooth muscle. Subject to breaking open at anytime and would cause bleeding in the Subarachnoid space.

Other Intracranial Hemorrhage (often Traumatic)

Epidural hematoma, subdural hematoma Related to a head injury

Case #5: Epidural Hemorrhage

18 year-old man is struck in the head by a fast ball during a game of baseball. He initially complains of headache, then continues to play ball. Two hours later, he is sleepy and wants to take a nap (at 6 pm). At 7 pm, he is unresponsive. Blood clot sitting on top of the dura Not a normal location for blood to be Fracture of the skull bone Rupture of Middle Meningeal Artery Compresses the dura against brain Remove clot to remove pressure on brain. Look at the CT for skull fracture (may not be there). In a young child suffering an Epidural Hemorrhage, there may not be a skull fracture shown on CT but damage will still be there.

Subdural Hemorrhage
Head injury results in a vein rupturing and blood will form between the dura and the brain. It forms a slightly different shape of clot than the Epidural Hematoma. This would result in subtle changes at first show up weeks later with complaints.

Contusions
Brain bruise Gyral Crests, temporal lobes, olfactory bulbs /tracts (inferior frontal) Plaque jaune (yellowish color)

Cerebral Edema
Rigid encasement of brain, spinal cord (skull, vertebral bodies, dura) Types: vasogenic, cytotoxic, interstitial

Possible Underlying Conditions:

1. 2. 3. 4. Tumor Infarct or hemorrhage DAI: diffuse axonal injury Abscess Subfalcine (cingulate) Anterior cerebral artery compression Transtentorial (uncal) Cranial nerve III compression Posterior cerebral artery compression Occipital lobe infarction Hemorrhages in brainstem (Duret) Cerebellar tonsillar Medulla compression

Sites of Herniation

Diffuse Axonal Injury

Damage to axons as may occur in angular acceleration Often seen in motor vehicle accidents Long tracts of the white matter at are the most risk of damage Can lead to extreme cerebral edema

Cerebral Edema (continued):

Tonsilar Cerebellar Herniation Dusty gray coloration Swollen tissue around the medulla Compression of medulla -- death

Durets Hemorrhage Linear blood

Hydrocephalus
Excess CSF decrease resorption (more common) or overproduction Ventricular expansion, elevated Intracranial Pressure Relevant closure of sutures o In children with suture still present, can lead to increased head size Ex vacuo (AD): very large ventricles

Quiz:
Lesion in the right hemisphere Appears to be taking over Caudate, Putamen, GP Differential: Vascular Malformation AVM or Cavernous Angioma Cavernous ANgioma is back to back BV without intervening brain tissue this has intervening tissue so more likely AVM.