CNS pathology Flashcards
1
Q
Stains for CNS cells
A
- H&E
- Luxol blue: stains myelin blue (white matter dark blue, gray matter very light blue)
- Silver stain: stains neurofilaments black
- Immunoperoxidase stains to stain for synaptic protein (synaptophysin), localized neurofilaments or NTs
2
Q
Ischemic cell change (red neuron)
A
- Red is dead, occurs in response to deprivation of O2
- Btwn 8-24hrs after insult, neuron shrinks and cytoplasm becomes eosinophilic (pink/red on H&E)
- Nucleus is darkly stained, then lost
- Changes are irreversible
- Insult requires deprivation of O2 to tissue for several minutes for irreversible damage, but then 8-24hrs is required for these changes to be observed
- Cellular changes: depletion of ATP, acidosis, impaired reuptake of GLU by glial cells and resulting excitotoxicity, accumulation of intracellular Ca, ROS generation
3
Q
Wallerian degeneration
A
- Occurs when an axon is transected by trauma
- Axon and myelin distal to transection degenerate, leading to impaired axonal transport
- Disappearance of neurofibrils and breaking of axon into short fragments (parts are phargocytosed)
- This occurs over weeks in PNS and months in CNS
- Sprouting of new axons from cell body possible in PNS, but not CNS
4
Q
Central chromatolysis
A
- Occurs after transection injury to neuron’s axon, usually seen in large motor neurons
- Consists of swelling of cell body, dissolution of nissl substance, and migration of nucleus to the periphery of the body
- Reversible
5
Q
Distal axonopathy
A
- Degeneration of the axon and myelin first develops in the most distal part of the axon
- The axon “dies back”
- Usually a result of toxins (pesticides, acrylamide, ect) or metabolic problems (diabetes, renal failure, alcoholism)
- When the metabolic needs of the cell are not met, the most distal part of the axon dies first
6
Q
Inclusion bodies
A
- Abnormal deposits in neurons
- Stains w/ silver stain: cytoplasmic neurofibrilary tangles (AD) and Pick bodies (Pick disease)
- Stains w/ H&E: cytoplasmic lewy bodies (PD) and negri bodies (rabies)
- Stains w/ H&E: nuclear cowdry type A (herpes and CMV)
6
Q
Oligodendrocytes
A
- All glia are neuroectodermal in origin (except for microglia, which are mesodermal- bone marrow- derived)
- Reside mostly in white matter (also some in grey) and myelin ate the axons
- Have small, round nuclei and no apparent cytoplasm
7
Q
Myelin loss (pathologic oligodendrocytes)
A
- Demonstrated by luxol stain, turing myelin blue
- Demyelinating disease such as MS (autoimmune) leave large plaques of absent blue color (axons left intact)
- MS plaques are usually periventricular, larger, and more confluent that PML
- Progressive multifocal leukoencephalopathy (PML) forms small plaques of demyelination (most severe at grey-white matter junctions) when oligodendrocytes die and myelin degenerates
- Oligodendrocytes can die from viruses, like the papova virus (causes PML). This virus results in a homogenous, glassy nuclear inclusion in the oligos
- Leukodystrophies are due to genetic mutations. Myelin is abnormally formed and is unstable so it breaks down
9
Q
Astrocytes 1
A
- Astrocytes present in gray and white matter, have large oval nuclei (larger than oligo’s) with more euchromatin than oligo’s
- Processes can only be seen when stained w/ glial fibrillary acidic protein (GFAP)
- These processes surround the small arteries of the brain and play a role in maintaining the BBB and ionic environment
9
Q
Astrogliosis (gliosis)
A
- Astrocytes respond to almost any brain injury by gliosis, which includes proliferation and hypertrophy
- Cytoplasm becomes very apparent and eosinophilic due to GFAP (referred to as gemistocytes)
- This process does not result in fibrosis
10
Q
Astrocytes 2
A
- Astrocytes present in gray and white matter, have large oval nuclei (larger than oligo’s) with more euchromatin than oligo’s
- Processes can only be seen when stained w/ glial fibrillary acidic protein (GFAP)
11
Q
Microglia
A
- Derived from bone marrow (mesoderm), infiltrate developing brain along w/ blood vessels
- Slow turnover during life
- Appear as small elongated, dark-staining nuclei
- Can respond to injury by differentiating and acting as macrophages
12
Q
Reactive microglial cell
A
- Activated microglia (due to brain injury or local immune response) look rod-shaped
- May up regulate expression of MHC and inflammatory cytokines
13
Q
Macrophage response
A
- Microglia may differentiate into macrophages, especially during brain necrosis
- The macrophages phagocytose the tissue debris (lipid-laden macrophages, or glitter cells)
- Monocytes may enter brain after injury, and differentiate into macrophages as they do so
14
Q
Microglial nodule
A
- Microglia may respond to single damaged neurons in encephalitis, by encircling the neuron and phagocytosing it (neurophagia)
- This results in the formation of a microglial nodule
- Microglial nodules may also be present in white mater, especially in HIV encephalitis
15
Q
Multinucleated giant cell reaction
A
- Formed either from fusion or failure to divide
- In HIV encephalitis groups of microglial cells may accumulate in the white matter
- Some will fuse to form the multinucleate giant cell
- Can often be seen in AIDS dementia pts
16
Q
Vasogenic edema
A
- Loss of integrity of BBB (broken tight junctions) may result in entrance of excess water and solutes into extracellular space of brain
- The fluid collect predominantly in white matter
- Results in increased brain volume and intracranial pressure, leads to mass effect
18
Q
Vasogenic edema
A
- Loss of integrity of BBB (broken tight junctions) may result in entrance of excess water and solutes into extracellular space of brain
- The fluid collect predominantly in white matter
- Results in increased brain volume and intracranial pressure (new water entering brain)
18
Q
Hypoxia vs ischemia
A
- When the brain is deprived of O2 (hypoxia) it is usually due to the brain being deprived of blood (ischemia)
- Pure hypoxia causes mostly reversible (to an extent) failure of electrical activity and synaptic transmission, and doesn’t cause necrosis
- Ischemia results in decreased O2, glc, and a build up of toxic metabolites and thus is much more damaging
19
Q
Cytotoxic edema
A
- Toxic or metabolic events that affect normal neuronal and glial membranes may result in intracellular accumulation of fluid, or lysing of cells
- More likely to affect cells in gray matter and usually do not lead to mass effect (not introducing any new water- just releasing the water from cytoplasm)
20
Q
Selective neuronal necrosis (global hypoxia-ischemia)
A
- Cells in the CNS have differing sensitivity to hypoxia-ischemia (during intermediate severity of ischemia)
- Neurons (especially cortical neurons) are more vulnerable to ischemia than glial cells and endothelial cells (most vulnerable layers in cortex: layers 3 and 5)
- Neurons in brainstem and spinal cord are more resistant to hypoxia-ischemia than neurons in the cortex
- Water-shed areas are first to be affected because they lack sufficient collateral circulation (i.e. hippocampus), usually btwn ACA, MCA, and PCA
- Histologic changes seen only after 12-24 hrs of insult
- Results in eosinophilic ischemic necrosis: neurons shrink, cyto becomes eosinophilic, nucleus becomes blurry. Eventually the neuron disappears
21
Q
Selective neuronal necrosis (global hypoxia-ischemia)
A
- Cells in the CNS have differing sensitivity to hypoxia-ischemia (during intermediate severity of ischemia)
- Neurons (especially cortical neurons) are more vulnerable to ischemia than glial cells and endothelial cells (most vulnerable layers in cortex: layers 3 and 5)
- Neurons in hippocampus most susceptible to hypoxia than another part of brain (lose recent memory)
- Neurons in brainstem and spinal cord are more resistant to hypoxia-ischemia than neurons in the cortex
- Water-shed areas are first to be affected because they lack sufficient collateral circulation (i.e. hippocampus), usually btwn ACA, MCA, and PCA
- Histologic changes seen only after 12-24 hrs of insult
- Results in eosinophilic ischemic necrosis: neurons shrink, cyto becomes eosinophilic, nucleus becomes blurry. Eventually the neuron disappears
22
Q
Focal ischemia and infarction
A
- Leads to deprivation of a specific area of blood, causing excitotoxicity (increased extracellular GLU and ASP), increased lactic acid and tissue acidosis
- The center of the infarct (core) is unsalvageable
- But btwn the core and the healthy tissue is the penumbra, an area of constrained blood but partially preserved metabolism
- The penumbra is at risk of infarction, yet potentially salvageable
- Requires 12-24hrs after insult for histologic changes to be seen
23
Q
Causes of CNS infarcts
A
- Atherosclerosis predominantly affects larger vessels (common carotid, especially at bifurcation, MCA, and basilar a)
- Atheroscelrotic plaques can lead to thrombotic occlusions, which do not move unless they embolize (form at site of infarction)
- Most large infarcts are caused by thromboembolisms of the MCA
- Hemorrhages are most often seen in infarcts of embolic origin
24
Q
Microscopic features of infarcts
A
- Earliest changes: pallor and vacuolization (falls apart) of neuropil, endothelial swelling and eosinophilic ischemic necrosis (EIN)
- Next there are some PMNs infiltrating, followed by macrophages
- Finally there is cavitation w/ surrounding gliosis
- During gliosis and PMN/mac infiltration the brain appears hypercellular
25
Q
Embolic vs thrombotic infarction
A
- Embolic infarctions are more common, and the heart is frequently the source (arrhythmias such as a fib and vulvar disease)
- Other sources: bits of thrombus, atherosclerotic plaque, talc protein, others
- The MCA is most often affected by embolic infarcts
- Embolisms are more likely to cause multiple infarcts than thrombotic
- Embolic infarcts are more likely to be complicated by hemorrhage into infarcted tissue (blood is restored to dead tissue and the capillaries hemorrhage)
- Always check for hemorrhage (indicates embolic) and multiple infarcts (indicates embolic)
26
Q
Vasculitis infarct
A
- Vasculitis (inflammation of blood vessels) can cause infarction
- May be part of systemic vasculitis or isolated to CNS
- May be multiple and hemorrhagic, and has many causes (such as infection)
- Often suspected but rarely Dx
- Vessel walls infiltrated by inflammatory cells, damage to vessel wall can result in thrombosis
27
Q
Lacunar infarcts
A
- Type of ischemic small vessel disease (HTN high risk factor for this and intracerebral hemorrhage)
- Small infarcts (often multiple) due to small vessel atherosclerosis w/ chronic HTN and diabetes being major risk factors
- Often found in pons and basal ganglia
- May be asymptomatic, or isolated neurological deficits (or dementia if multiple)
28
Q
Intracerebral hemorrhage
A
- Associated with HTN and often occur in basal ganglia, thalamus, brainstem, or cerebellum
- Will cause a mass effect
- The ipsilateral ventricle will be small, while the contralateral one will be large due to obstruction of CSF flow
- The obstruction to CSF flow and the mass affect both raise intracranial pressure
29
Q
Fibrinoid change
A
- Deposition of proteins in vessel walls, causes damage to the walls
- Due to chronic HTN (less severe, more chronic than fibrinoid necrosis)
- If extreme HTN, the vessels may undergo fibrinoid necrosis
30
Q
Amyloid angiopathy
A
- Amyloid stains w/ congo red, gives a green birefringence under polarized light
- Deposition of amyloid in cerebral vessels is another way of developing intracerebral hemorrhage (sometimes multiple)
- These hemorrhages are usually located superficially in the cerebral hemispheres, with a predilection for the occipital lobe
- Common in AD
31
Q
Cerebral aneurysm
A
- Can cause excruciating headaches, loss of consciousness, stiff neck, subarachnoid hemorrhage
- Blood in subarachnoid space causes: blockage to CSF flow, vasospasms (other vessels may hemorrhage)
- Often arise at bifurcations, circle of willis and communicating arteries, basilar artery
- Often are multiple and rebleed, often fatal
- Can result in intraventricular and intracerebral hemorrhage
31
Q
Vascular malformations
A
- Congenital problems that cause abnormal flow, hemorrhage, seizures, and focal deficits
- Usually superficial, typically over cerebral convexity
- Can easily be seen on angiogram, where its a large bundle of unorganized vessels
32
Q
Cavernous hemangioma
A
- Back-back thin walled vessels
- Located more deeply in the brain usually than AVMs
- Most common symptom is seizure by also may bleed
- Typically has less brain parenchyma btwn vessels than AVMs
- Can often be asymptomatic
33
Q
Arteriovenous malformations (AVM)
A
- Congenital problems that cause abnormal flow, hemorrhage, seizures, and focal deficits
- May be asymptomatic, but are more dangerous than cavernous hemangiomas
- Usually superficial, typically over cerebral convexity
- Can easily be seen on angiogram, where its a large bundle of unorganized vessels
- Often will have arteries connecting to veins without going through a capillary bed (microscopically seen as many vessels of various sizes )
- Tend to bleed b/c arteriole blood under high pressure directly enters veinules that can’t handle the pressure
- The vessel walls and size of vessels vary btwn one another (can be fibrotic)
34
Q
Uncal herniation
A
- A complication of any space-occupying intracerebral lesion (mass affect), including hemorrhage and infarction
- Uncus herniates thru the incisura of the tentorium and compresses the brainstem
- Can lead to hemorrhages in the midline brainstem (duret hemorrhages- from shearing of other arteries)
- PCA can be affected by duret hemorrhages
35
Q
Cavernous hemangioma
A
- Back-back thin walled vessels
- Located more deeply in the brain usually than AVMs
- Most common symptom is seizure by also may bleed
- Typically has less brain parenchyma btwn vessels than AVMs, vessels tend to be thinner (fibrosis in the walls of vessels)
- Can often be asymptomatic
36
Q
Types of hematomas
A
- Epidural: lesion in the middle meningeal artery, bleeds above the dura and causes mass effect
- Subdural: lesion in the bridging vein, leads to slowly enlarging hematoma that causes mass effect
- Subarachnoid: lesion in the cerebral arteries, causes blood to enter CSF (worst headache ever, drowsiness, confusion), no mass effect
- Intracranial hemorrhage: lesion of a vessel within the brain tissue, causes mass effect
