CNS Histology and Infections Flashcards by Chris Allison

What are Virchow-Robin spaces?

Subarachnoid and subpial spaces that surround blood vessels in the brain.

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What are arachnoid villi?

Same thing as arachnoid granulations - penetrations into the dural sinuses that conduct CSF into the circulation.

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Is the arachnoid normally clear or opaque?

Normal is clear. The arachnoid becomes opaque with age, but opacity can also be caused by pathological process.

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Review: What are Nissl bodies?

Rough ER, basophilic, present in neurons (unless they’re dying)

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How can you tell a neuron’s axon from its dendrite histologically?

The axon hillock lacks Nissl substance.

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What stain can you use to identify astrocytes histologically?

GFAP (immunostain)

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How do the nuclei of oligodendrocytes contrast from those of astrocytes?

Those of oligos are smaller, rounder, stain darker, and usually lack nucleoli.

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What are two types of specialized glial cells that resemble epithelial? What makes them not real epithelia?

Ependyma and choroid plexus. They lack a basement membrane.

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Where are the ependyma located?

They line the ventricles.

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Where is there choroid plexus?

Lateral ventricles and 4th ventricle.

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What are the six layers of the neocortex?

I: Molecular
II: External granular
III: External pyramidal
IV: Internal granular
V: Internal pyramidal
VI: Plexiform

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What cortex might not have 6 layers? Two specific examples of such structures?

Archi/palleocortex has fewer than 6 layers. Hippocampus and cerebellum.

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Review: How many layers does the cerebellar cortex have, and what are they?

3: Molecular, Perkinje, and Granular. (molecular is outermost)

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What are 3 patterns of neuron injury in the CNS?

Acute ischemic injury, chronic injury (cell loss), neuronal inclusions

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What’s the term for how glial cells respond to injury?

Reactive gliosis

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2 modes of inflammatory cell response to CNS injury?

Microglia-based

Inflammatory infiltrates

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Describe the changes that happen to neurons in acute ischemic injury? (3 things)

“Red” neuron:
Shrunken cell body, intense cytoplasmic eosinophilia with complete loss of Nissl basophilia, dark nucleus without a nucleolus.

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What region of the cerebellum is most sensitive to ischemic injury?

The Perkinje cells.

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What are 2 types of normal (non-pathological) neuronal cytoplasmic inclusions?

Lipofuschin (normal in aging neurons, esp. large motorneurons)
Neuromelanin - seen in catecholaminergic neurons (substantia nigrata, locus ceruleus, dorsal motor nucleus)

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What are 3 pathological neuronal inclusions?

Cytoplasmic flame-shape neurofibrillary tangles of AD.
Cytoplasmic round Lewy bodies of PD etc.
Intranuclear / cytoplasmic viral inclusions of CMV etc.

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3 changes that happen to astrocytes during gliosis?

Hypertrophy, hyperplasia, and increased connections

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What are 4 ways that infectious organisms access the CNS? Which is most common?

Hematogenous spread (most common)
Local extensions (from paranasal sinuses, middle ear)
Retrograde transport from PNS (eg. HSV, rabies)
Direct implantation (trauma, surgery, intrathecal injection)

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4 predisposing factors for CNS infection.

Immunosuppression
Mechanical devices / surgical intervention (e.g. shunts)
Anatomical congenital malformations.
Hyposplenism and asplenia (poorer clearance of encapsulated bacteria)

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What’s pachymeningitis?

Spread of infection into layers of dura mater.

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What's meningitis/leptomeningitis? (What does "lepto-" mean?)

Inflammation of pia and arachnoid. ("Lepto-" = thin)

What's encephalitis? (what kind of inflammation / etiological agent)

Inflammation of brain parenchyma with mononuclear cells- "chronic inflammation." Usually caused by viruses.

What's cerebritis? what kind of inflammation / etiological agent)

Inflammation of brain parenchyma with neutrophils - "acute inflammation." Usually caused by bacteria.

What's myelitis?

Inflammation of spinal cord.

What's poliomyelitis?

Inflammation of spinal gray matter.

What's ganglionitis?

Inflammation of dorsal root ganglia.

What's radiculitis?

Inflammation of intradural spinal nerve roots.

Which categories of organisms induce granulomatous inflammation in the CNS? (name 4)

Mycobacteria, spirochetes, fungi, parasites

With what type of inflammation are microglial nodules associated?

Viral encelphalitis.

4 CNS compartments for bacterial infection? Processes associated with those compartments?

Epidural space - epidural abscess Subdural spaces - subdural abscess or empyema (pus) Subarachnoid space - leptomeningitis/meningitis Parenchyma - abcess, diffuse cerebritis

What's the most common location / process associated with bacterial CNS infection?

Leptomeningitis/meningitis in the subarachnoid space.

3 most common bacterial species that cause meningitis?

S. pneumoniae, N. meningiditis, and H. influenzae

3 most common bacterial species that cause meningitis in neonates (0 - 6mo)?

Group B Strep E. coli L. monocytogenes

3 most common bacterial species that cause meningitis is children / adults 6mo - 60 years?

S. pneumoniae, N. meningiditis, H. influenzae

2 most common bacterial species that cause meningitis in adults > 60 years and immunosuppressed pts?

S. pneumoniae, L. monocytogenes

2 broad sources of infections that cause brain abscesses?

Local (sinusitis-otitis, mastoiditis), hemotogenous

2 origins of hematogenous seeding of brain abscesses? Which is most common?

Most common: septic emboli, esp. from bacterial endocarditis Cyanotic congenital cardiac disease (i.e. right to left shunts, ostensibly because venous bacteria are getting pumped straight to the brain)

Most common organisms that cause brain abscesses? (name 2+)

S. aureus, Streptococci, but often polymicrobial.

3 features of the gross pathology of brain abscesses?

Discrete, round lesions with central liquefactive necrosis / purulent stuff. Surroundin fibrotic capsule. Mass effect, possibly causing herniation.

How do brain abscesses appear on imaging?

"Ring-enhancing lesions"

Describe early vs. late microscopic findings of brain abscesses. About how long does it take for the "late" processes to appear?

Early: lots of PMNs Late: PMNs and debris surrounded by fibroblasitc collagenous capsule. Capsule starts appearing at about 10 days.

What's the most common form of mycobacterial CNS infection?

Tuberculous meningitis.

4 pathological features of tuberculous meningitis?

Necrotizing granulomas, lymphocytes, multinucleated giant cells, and fibrosis. (Pretty standard stuff for a TB granuloma)

3 forms of neurosyphilis?

``` Meningovascular neurosyphilis Paretic neurosyphilis (damage to cerebral cortex) Tabes dorsalis ```

4 features of neuroborreliosis?

Aseptic lymphocytic meningitis Facial nerve palsy Neuropathies / polyradiculitis Encephalopathy

4 manifestations of CNS viral infections? What tissue is affected in each?

"Aseptic" meningitis: Inflammation restricted to meninges. Polioencephalitis (encephalitis) / poliomyelitis: Hits gray matter. Panencephalitis/panmyelitis: Hits both gray and white matter. Leukoencephalitis: Hits white matter.

What viruses are most commonly associated with "aseptic" meningitis?

Enterovirus (>80%)

What viruses are most commonly associated with (polio)encephalitis/poliomyelitis?

poliovirus, *arboviruses*, coxsackieviruses, echoviruses, tick-born, rabies, etc. etc.

What viruses are most commonly associated with panencephalitis/panmyelitis?

HSV (necrotizing herpresviruses), and many non-necrotizing viruses such as HIV.

What viruses are most commonly associated with leukoencephalitis?

JC virus, HIV

What do you see in an LP of "aseptic" meningitis?

Increased lymphocytes and mononuclear cells, absence of bacteria or fungi

What type of acute viral encephalitis shows seasonality?

That caused by arboviruses (e.g. West Nile Virus)

4 pathological features of acute viral encephalitis?

Perivascular inflammatory infiltrate Microglial nodules Neuronophagia Intranuclear viral inclusions

What pattern of necrosis is classical for HSV-1 encephalitis?

Bilateral, assymetric hemorrhagic necrosis of the temporal lobes.

What are the only 2 ways you'll see CMV encephalitis?

Intrauterine infection. Immunosuppression.

Micro review: Characteristic pathological finding of rabies encephalitis?

Negri bodies

6 manifestations of CNS fungal infections?

Diffuse encephalitis Leptomeningitis Fungal mycetoma of the meninges Space-occupying lesions (granulomas, abscesses) Septic infarct from vascular invasion/thrombosis Hemorrhage from mycotic aneurysm formation / rupture

Micro review: Microscopic difference between Aspergillus and mucor?

Mucor hyphae are wider, non-septate, (and branch at angles closer to 90 degrees)

2 classical clinical scenarios associated with mucor?

Diabetic ketoacidosis, rhinocerebral disease

What's the one organism we should know about that causes amebic encephalitis?

Naegleria fowleri

Where do N. fowleri live when causing amebic encephalitis? What do they look like?

Live in subarachnoid space. They look somewhat like macrophages. Vesicular nucleus with prominent nucleolus.

What's the most common helminthic CNS disease? How do people get it?

Cysticercosis. Eating undercooked pork.

Grossly, what does cysticercosis look like?

Cysts errywhere. (Parenchyma, meninges, ventricles, and rarely the spinal cord).

What are 4 notable CNS infections that hit immunocompromised hosts?

Cryptococcal meningitis, toxoplasmosis, HIV encephalopathy, progressive multifocal encephalopathy.

Pathology seen in cryptococcal meningitis: Where? What inflammatory cells?

Gelatinous, pseudocystic dilations of Virchow-Robin spaces ("bubbles") Minimal inflammatory reaction - with lymphos, plasma cells, eosinophils, and multi-nucleated giant cells.

Micro review: Classic diagnostic tool for cryptococcus?

India ink stain of CNS. But culture or cryptococcal antigen assays usually work fine.

Pathological feature of toxoplasmosis?

Multiple ring-enhancing lesions - abscesses.

What unusual cells are seen in HIV encephalitis?

Multinucleated giant cells.

What parts of the brain does HIV encephalitis hit?

Subcortical white matter, basal ganglia, brainstem.

Pathological features of HIV encephalitis? 3-4 things.

Widespread low-grade inflammation. Perivascular and parenchymal lymphos and microglial nodules. Multinucleated giant cells. Patchy demyelination and variable gliosis in the white matter (leukoencephalopathy).

What virus causes progressive multifocal leukoencephalopathy (PML)?

JC Virus

For what cells is JC virus tropic?

Oligodendrocytes

4 pathological features of progressive multifocal leukoencephalopathy?

Ill-defined demyelinating lesions Lipid-laden macrophages Intranuclear viral inclusions ("Glassy nuclei") Bizarre astrocytes with atypia.

CNS Histology and Infections Flashcards

She packed a lot of info into this lecture. Most of the details are here... but as they can only ask a small number of questions per lecture on the test, broader concepts are emphasized. Hopefully.