Neuropathology I Flashcards
Why does the brain have a high oxygen demand?
The brain is only 2% of body weight but receives 15% of cardiac output and uses 20% of total body oxygen.
What happens if the brain’s oxygen supply is interrupted?
Even a few minutes of ischemia (lack of oxygen) can cause irreversible brain damage
What type of metabolism do neurons rely on?
Neurons are predominantly aerobic and require continuous oxygen to function
Which brain areas are most sensitive to oxygen deprivation?
- Adults: Hippocampus, 3rd/5th/6th cortical layers, Purkinje cells, and watershed areas
- Infants: Brainstem nuclei
How is the brain’s blood supply divided between anterior and posterior systems and what do they form?
- Anterior flow: via internal carotid arteries
- Posterior flow: via vertebral arteries→ basilar artery
**these arteries anastomose and form the circle of Willis
What is an Atheroma?
fatty deposit that forms inside the walls of arteries and occurs most commonly in the circle of Willis
what is a Stroke?
sudden onset of neurological symptoms caused by a problem in the brain’s blood supply
what is an Ischemic Stroke ?
blocked blood vessel in the brain reduces or stops blood flow, depriving brain tissue of oxygen
what is a Hemorrhagic Stroke?
ruptured blood vessel that leaks blood into or around the brain
- Intraparenchymal hemorrhage: bleeding inside the brain tissue
- Subarachnoid hemorrhage: bleeding around the brain
What is a Transient Ischemic Attack (TIA)?
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
what are the causes of an Ischemic Stroke?
- Cardioembolism
- Large vessel atherosclerosis (intracranial and extracranial)
- Small vessel disease (lacunar strokes)
- Uncommon cases of stroke
- Idiopathic
What is cardioembolism, and how common is it in ischemic stroke?
occurs when a blood clot forms in the heart and travels to the brain and accounts for up to 20% of ischemic strokes
What are key clinical features of cardioembolic strokes?
- Can affect multiple vascular territories
- Causes CNS and systemic emboli
- Has the highest in-hospital mortality
- Leads to more functional limitations after discharge
What are common sources of cardioembolic strokes?
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)
what is Large Artery Atherosclerosis?
buildup of fatty plaques in the arteries, which can narrow or block blood flow to the brain and cause ischemic stroke
Where can large artery Atherosclerosis happen?
- Extracranial Arteries
* Internal carotid artery (ICA)
* Common carotid artery (CCA)
* Vertebral artery - Intracranial Arteries
* Middle cerebral artery (MCA)
* Anterior cerebral artery (ACA)
* Posterior cerebral artery (PCA)
* Basilar artery
What are Lacunar Infarcts (Small Vessel Strokes)?
Small strokes caused by blockage in tiny, deep brain arteries often due to hypertension-related vessel damage (small vessel hyalinosis or microatheroma)
What are the two Lacunar Infarcts (Small Vessel Strokes) types and what are they based on?
based on the area affected in the subcortical region (e.g., basal ganglia, thalamus)
- Internal capsule: → Pure motor stroke
- Thalamus: → Pure sensory stroke
what is Hypertensive Small Vessel Disease and what causes it?
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
what are Charcot-Bouchard Aneurysms?
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
what are the uncommon causes of Ischemic Strokes?
- 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
what are the modifiable and non-modifiable risk factors for Strokes?
- Non-modifiable
- Age
- Gender
- Hereditary
- Modifiable
- Hypertension
- Cardiac disease
- Diabetes
- Hypercholesterolemia
- Cigarette smoking
- Alcohol
what are the treatment goals in Acute Ischemic Stroke?
- Reperfusion to restore cerebral blood flow
- Supportive Care to protect the brain and prevent complications
- Prevent Recurrence of stroke through antithrombotic therapy and finding the cause of the stroke
during ischemia what is the first visible histological change (6-12 hrs)?
damaged or dying neurons called red neurons appear that have eosinophilic cytoplasm, hyper-chromatic nuclei and have lost their nissl granules
what happens during the first 1-3 days after an Ischemic Stroke?
red neurons, brain tissue becomes loose and breaks down (neuropil rarefaction), necrosis begins and neutrophils begin to infiltrate
what happens 4-7 days after an Ischemic Stroke?
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
what happens 2-3 weeks/months after an Ischemic Stroke?
- Gliosis: support cells (astrocytes) form a scar in response to injury
- Cystic cavity formation: dead tissue is removed, leaving behind empty fluid-filled spaces
What is an intracerebral hypertensive hemorrhage and where does it commonly occur?
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%
What is a non-traumatic subarachnoid hemorrhage and its most common cause?
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
What are berry aneurysms (saccular or congenital aneurysms) and where do they usually occur?
intracranial arterial aneurysms occurring mostly at branch points in the Circle of Willis where 20–30% of affected people have multiple aneurysms
berry aneurysms have an increased risk in what individuals?
people with adult-onset polycystic kidney disease
what aneurysms usually do not cause subarachnoid hemorrhage (SAH)?
rare aneurysms like atherosclerotic, mycotic, traumatic, or dissecting that are not commonly found at Circle of Willis branch points
how do Subarachnoid Hemorrhage (SAH) usually present?
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
What is vasculitis, and what layers of the blood vessel wall are involved?
inflammation of blood vessel walls including the three layers intima (endothelial layer), media (smooth muscle) and adventitia (outer connective tissue layer)
What is the etiology of vasculitis and how is it categorized?
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)
What is temporal arteritis and who is most affected?
also called giant cell arteritis, it is a large vessel vasculitis that most often affects females over 50 years old
What are the main symptoms of temporal (giant cell) arteritis?
- Headaches (temporal artery involvement)
- visual disturbances (ophthalmic artery involvement)
- Jaw claudication
- Flu-like symptoms
What are the key histological findings in temporal (giant cell) arteritis?
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
what is the difference between a seizure and epilepsy?
- 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
How common is epilepsy, and why is it significant?
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
What are the major challenges and impacts of epilepsy?
Seizures often remain uncontrolled in many patients despite treatment and healthcare costs are high due to long-term management needs
What are the future goals in epilepsy treatment and management?
Cure or prevention of epilepsy remains the ultimate goal but in the meantime, the aim is optimal seizure control for most patients
What are the known and unknown causes of epilepsy?
~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
Why are infants and young children at higher risk for seizures, and why is early diagnosis important?
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
What are the consequences of long-standing epilepsy (over 5 years) in children?
Developmental delays
Cognitive impairment
Behavioral problems, including:
- Aggression or self-aggression
- Attention deficits
how is Epilepsy diagnosed?
- History
- Electroencephalography (EEG)
- MRI
- Neurological exam
- Laboratory tests
what are the three most common brain abnormalities linked to epilepsy?
- Hippocampal sclerosis (HS)
- Cortical dysplasia
- Low-grade tumors
What is pathological definition of Hippocampal Sclerosis (HS)?
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
What does “neuronal loss and gliosis” mean in the context of hippocampal sclerosis?
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
What is focal cortical dysplasia, and how is it related to epilepsy?
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
What is Focal Cortical Dysplasia (FCD) and how is it classified?
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
What defines FCD Type 1 and what are its subtypes?
Architectural abnormalities without cytological changes
Subtypes:
- 1A: Vertical microcolumns
- 1B: Abnormal lamination
- 1C: Vertical and horizontal abnormalities
What defines FCD Type 2 and what are its subtypes?
Includes cytological changes
Subtypes:
- 2A: Dysmorphic neurons
- 2B: Dysmorphic neurons + balloon cells
What defines FCD Type 3 and what are its subtypes?
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)
What are white matter-related lesions in FCD, and what is mMCD?
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).
