Neuropathology I

Question 1

Why does the brain have a high oxygen demand?

Answer 1

The brain is only 2% of body weight but receives 15% of cardiac output and uses 20% of total body oxygen.

Question 2

What happens if the brain’s oxygen supply is interrupted?

Answer 2

Even a few minutes of ischemia (lack of oxygen) can cause irreversible brain damage

Question 3

What type of metabolism do neurons rely on?

Answer 3

Neurons are predominantly aerobic and require continuous oxygen to function

Question 4

Which brain areas are most sensitive to oxygen deprivation?

Answer 4

• Adults: Hippocampus, 3rd/5th/6th cortical layers, Purkinje cells, and watershed areas
• Infants: Brainstem nuclei

Question 5

How is the brain’s blood supply divided between anterior and posterior systems and what do they form?

Answer 5

• Anterior flow: via internal carotid arteries
• Posterior flow: via vertebral arteries→ basilar artery
  **these arteries anastomose and form the circle of Willis

Question 6

What is an Atheroma?

Answer 6

fatty deposit that forms inside the walls of arteries and occurs most commonly in the circle of Willis

Question 7

what is a Stroke?

Answer 7

sudden onset of neurological symptoms caused by a problem in the brain’s blood supply

Question 8

what is an Ischemic Stroke ?

Answer 8

blocked blood vessel in the brain reduces or stops blood flow, depriving brain tissue of oxygen

Question 9

what is a Hemorrhagic Stroke?

Answer 9

ruptured blood vessel that leaks blood into or around the brain
- Intraparenchymal hemorrhage: bleeding inside the brain tissue
- Subarachnoid hemorrhage: bleeding around the brain

Question 10

What is a Transient Ischemic Attack (TIA)?

Answer 10

temporary blockage of blood flow to the brain, causing stroke-like symptoms that go away on their own often called a “mini-stroke” and does not cause infarction
*****but 10% of people who have a TIA will go on to have a major stroke within 48 hours

Question 11

what are the causes of an Ischemic Stroke?

Answer 11

• Cardioembolism
• Large vessel atherosclerosis (intracranial and extracranial)
• Small vessel disease (lacunar strokes)
• Uncommon cases of stroke
• Idiopathic

Question 12

What is cardioembolism, and how common is it in ischemic stroke?

Answer 12

occurs when a blood clot forms in the heart and travels to the brain and accounts for up to 20% of ischemic strokes

Question 13

What are key clinical features of cardioembolic strokes?

Answer 13

• Can affect multiple vascular territories
• Causes CNS and systemic emboli
• Has the highest in-hospital mortality
• Leads to more functional limitations after discharge

Question 14

What are common sources of cardioembolic strokes?

Answer 14

Arrhythmias: e.g., atrial fibrillation
Left heart structural issues:
* LV (left ventricle) mitral thrombus
* Congenital heart failure
* Cardiac tumors
Valvular disease:
* Prosthetic heart valves
* Endocarditis (infection of heart valves)

Question 15

what is Large Artery Atherosclerosis?

Answer 15

buildup of fatty plaques in the arteries, which can narrow or block blood flow to the brain and cause ischemic stroke

Question 16

Where can large artery Atherosclerosis happen?

Answer 16

1. Extracranial Arteries
   * Internal carotid artery (ICA)
   * Common carotid artery (CCA)
   * Vertebral artery
2. Intracranial Arteries
   * Middle cerebral artery (MCA)
   * Anterior cerebral artery (ACA)
   * Posterior cerebral artery (PCA)
   * Basilar artery

Question 17

What are Lacunar Infarcts (Small Vessel Strokes)?

Answer 17

Small strokes caused by blockage in tiny, deep brain arteries often due to hypertension-related vessel damage (small vessel hyalinosis or microatheroma)

Question 18

What are the two Lacunar Infarcts (Small Vessel Strokes) types and what are they based on?

Answer 18

based on the area affected in the subcortical region (e.g., basal ganglia, thalamus)
- Internal capsule: → Pure motor stroke
- Thalamus: → Pure sensory stroke

Question 19

what is Hypertensive Small Vessel Disease and what causes it?

Answer 19

condition that affects the small arteries and arterioles in the brain through:
o Atherosclerosis
o Fibrinoid necrosis
o Arteriosclerosis: Thickened eosinophilic walls (hyalinosis)
o Microaneurysms

Question 20

what are Charcot-Bouchard Aneurysms?

Answer 20

small bulges that are dilated and thin form in small arteries or arterioles deep in the brain due to long-standing high blood pressure that can rupture and cause hemorrhaging

Question 20

what are the uncommon causes of Ischemic Strokes?

Answer 20

• Carotid/vertebral dissection
• Vasculopathy (e.g. vasculitis)
• Genetic (e.g. sickle cell disease)
• Hypercoagulable states (e.g. cancer, infection, Factor V Leiden etc.)
• Pregnancy, oral contraceptives

Question 21

what are the modifiable and non-modifiable risk factors for Strokes?

Answer 21

• Non-modifiable
• Age
• Gender
• Hereditary
• Modifiable
• Hypertension
• Cardiac disease
• Diabetes
• Hypercholesterolemia
• Cigarette smoking
• Alcohol

Question 22

what are the treatment goals in Acute Ischemic Stroke?

Answer 22

1. Reperfusion to restore cerebral blood flow
2. Supportive Care to protect the brain and prevent complications
3. Prevent Recurrence of stroke through antithrombotic therapy and finding the cause of the stroke

Question 23

during ischemia what is the first visible histological change (6-12 hrs)?

Answer 23

damaged or dying neurons called red neurons appear that have eosinophilic cytoplasm, hyper-chromatic nuclei and have lost their nissl granules

Question 24

what happens during the first 1-3 days after an Ischemic Stroke?

Answer 24

red neurons, brain tissue becomes loose and breaks down (neuropil rarefaction), necrosis begins and neutrophils begin to infiltrate

Question 25

what happens 4-7 days after an Ischemic Stroke?

Answer 25

neurons start disappearing (neuronal dropout), microglial/macrophage increase activity to clear dead material which means fewer neutrophils and more macrophages (microglia) instead and vascular proliferation starts

Question 26

what happens 2-3 weeks/months after an Ischemic Stroke?

Answer 26

- Gliosis: support cells (astrocytes) form a scar in response to injury - Cystic cavity formation: dead tissue is removed, leaving behind empty fluid-filled spaces

Question 27

What is an intracerebral hypertensive hemorrhage and where does it commonly occur?

Answer 27

bleeding into the brain tissue caused by chronic high blood pressure often due to the rupture of small Charcot-Bouchard aneurysms and occurs in the: Basal ganglia – most common (up to 50%) Cerebral lobes – up to 30% Brainstem or cerebellum – up to 20%

Question 28

What is a non-traumatic subarachnoid hemorrhage and its most common cause?

Answer 28

bleeding into the subarachnoid space most commonly caused by the rupture of a berry aneurysm, making it the 3rd most common type of stroke after cerebral infarction and hypertensive hemorrhage

Question 29

What are berry aneurysms (saccular or congenital aneurysms) and where do they usually occur?

Answer 29

intracranial arterial aneurysms occurring mostly at branch points in the Circle of Willis where 20–30% of affected people have multiple aneurysms

Question 30

berry aneurysms have an increased risk in what individuals?

Answer 30

people with adult-onset polycystic kidney disease

Question 31

what aneurysms usually do not cause subarachnoid hemorrhage (SAH)?

Answer 31

rare aneurysms like atherosclerotic, mycotic, traumatic, or dissecting that are not commonly found at Circle of Willis branch points

Question 32

how do Subarachnoid Hemorrhage (SAH) usually present?

Answer 32

sudden, severe headache with loss of consciousness (regains quickly), rebleeding is common, vasospasms and scarring of the meninges (leptomeninges) occurs ****but 25–50% of patients will die from the first aneurysm rupture

Question 33

What is vasculitis, and what layers of the blood vessel wall are involved?

Answer 33

inflammation of blood vessel walls including the three layers intima (endothelial layer), media (smooth muscle) and adventitia (outer connective tissue layer)

Question 34

What is the etiology of vasculitis and how is it categorized?

Answer 34

Cause is usually unknown and often non-infectious classified by vessel size * Large vessel (e.g. aorta and its main branches) * Medium vessel (muscular arteries) * Small vessel (arterioles, capillaries, venules)

Question 35

What is temporal arteritis and who is most affected?

Answer 35

also called giant cell arteritis, it is a large vessel vasculitis that most often affects females over 50 years old

Question 36

What are the main symptoms of temporal (giant cell) arteritis?

Answer 36

* Headaches (temporal artery involvement) * visual disturbances (ophthalmic artery involvement) * Jaw claudication * Flu-like symptoms

Question 37

What are the key histological findings in temporal (giant cell) arteritis?

Answer 37

o Granulomatous inflammation of vessel walls (giant cells and intimal fibrosis) o Disruption of elastic layer (by elastin stain) o Can be segmental (require biopsy of a long segment of vessel) o A negative biopsy does not exclude the disease

Question 38

what is the difference between a seizure and epilepsy?

Answer 38

- Seizure is brief, temporary disturbance in the electrical activity of the brain - Epilepsy is a disorder of recurring unprovoked seizures (“seizure disorder”) occurring at least twice, 24h apart

Question 39

How common is epilepsy, and why is it significant?

Answer 39

Epilepsy is the 2nd most common neurological disorder after stroke, affecting 1–2% of the global population (around 65 million people) and significantly affects the quality of life (QOL) of both patients and their families

Question 40

What are the major challenges and impacts of epilepsy?

Answer 40

Seizures often remain uncontrolled in many patients despite treatment and healthcare costs are high due to long-term management needs

Question 41

What are the future goals in epilepsy treatment and management?

Answer 41

Cure or prevention of epilepsy remains the ultimate goal but in the meantime, the aim is optimal seizure control for most patients

Question 42

What are the known and unknown causes of epilepsy?

Answer 42

~70% of cases, the cause of epilepsy is unknown (idiopathic) but epilepsy risk is higher in people with: - traumatic brain injury - stroke - Alzheimer’s disease - Autism - Brain tumors - Cerebral vascular abnormalities - Infections (e.g., meningitis, encephalitis) - Hereditary (genetic) factors

Question 43

Why are infants and young children at higher risk for seizures, and why is early diagnosis important?

Answer 43

Their brains are immature and still developing, which gives them a lower seizure threshold - Timely diagnosis and treatment are crucial due to early childhood being a critical window for learning key skills

Question 44

What are the consequences of long-standing epilepsy (over 5 years) in children?

Answer 44

Developmental delays Cognitive impairment Behavioral problems, including: - Aggression or self-aggression - Attention deficits

Question 45

how is Epilepsy diagnosed?

Answer 45

* History * Electroencephalography (EEG) * MRI * Neurological exam * Laboratory tests

Question 46

what are the three most common brain abnormalities linked to epilepsy?

Answer 46

1. Hippocampal sclerosis (HS) 2. Cortical dysplasia 3. Low-grade tumors

Question 47

What is pathological definition of Hippocampal Sclerosis (HS)?

Answer 47

condition marked by neuronal loss and gliosis within specific regions of the hippocampus and granule cell dispersion and axonal reorganization occuring in the dentate gyrus, disrupting normal circuitry

Question 48

What does "neuronal loss and gliosis" mean in the context of hippocampal sclerosis?

Answer 48

Neuronal loss mainly affecting mainly effecting CA1 and CA4/3 subfields of the hippocampus but the subiculum, CA2 neurons and granule cells are often preserved

Question 49

What is focal cortical dysplasia, and how is it related to epilepsy?

Answer 49

a microscopic architectural disorganization of neocortical neurons, often seen in patients with focal epilepsies that is commonly associated with drug-resistant epilepsy and can be difficult to consistently diagnose due to poor interobserver reproducibility in subtle lesions

Question 50

What is Focal Cortical Dysplasia (FCD) and how is it classified?

Answer 50

a malformation of cortical development that causes epilepsy most common in the frontal and temporal lobes that is classified into Types 1, 2, and 3

Question 51

What defines FCD Type 1 and what are its subtypes?

Answer 51

Architectural abnormalities without cytological changes Subtypes: - 1A: Vertical microcolumns - 1B: Abnormal lamination - 1C: Vertical and horizontal abnormalities

Question 52

What defines FCD Type 2 and what are its subtypes?

Answer 52

Includes cytological changes Subtypes: - 2A: Dysmorphic neurons - 2B: Dysmorphic neurons + balloon cells

Question 53

What defines FCD Type 3 and what are its subtypes?

Answer 53

architectural abnormalities with another principal lesion Subtypes include: - 3A: With hippocampal sclerosis (HS) - 3B: Adjacent to a tumor - 3C: Adjacent to a vascular malformation - 3D: Adjacent to an early-life acquired lesion (e.g., stroke, infection)

Question 54

What are white matter-related lesions in FCD, and what is mMCD?

Answer 54

mMCD (mild malformation of cortical development) that involves excessive heterotopic neurons, or oligodendroglial hyperplasia seen in epilepsy (MOGHE) that are not associated with other major lesions (like HS or tumors).