28. Neuropath: Infectious Diseases Flashcards
Osteitis: inflammation is where?
bone of skull/spine
Epidural empyema: inflammation is where?
pus in epidural space
pachymeningitis: inflammation is where?
dura
subdural empyema: inflammation is where?
pus below dura and above arachnoid
ventriculitis: inflammation is where?
ventricular lining
leptomeningitis: inflammation is where?
pia and arachnoid
meningitis: inflammation is where?
membranes (pia and arachnoid)
encephalitis: inflammation is where?
brain substance/parenchyma
myelitis: inflammation is where?
spinal cord
radiculitis: inflammation is where?
nerve root
neuritis: inflammation is where?
nerve
slow viruses aka prions: what is histopathology appearance, in general?
spongiform encephalitis
what is a prion?
infectious protein
CJD: what population is it most prevalent in? how does it present?
older people. will have subacute dementia evolving over a few months. may be social/cognition problems, visual probs. may be startle myoclonus. irreversible.
nvCJD: what is the origin of this disease? presentation?
new-variant CJD: this is mad cow as it appears in humans. tends to occur to younger people but presentation is similar to CJD.
Gerstmann-Straussler: presentation? prognosis?
genetic disease. causes cerebellar ataxia, and after a year or two patients become demented and die.
how do we know that prions are proteins?
they are sensitive to proteases.
CJD: gross brain appearance?
slight atrophy but otherwise normal
CJD: histological appearance?
extensive neuronal loss. causes gliosis, spongiform appearance. atrophy of white matter since neurons have gone and myelin is resorbed.
wtf is gliosis?
proliferation/hypertrophy of glial cells in response to insult. can lead to a glial scar.
we have prions normally: what is the difference between our normal prions and those that cause disease?
mutations cause pathologic variants.
general characterization of viral illnesses in the CNS?
can be dead in 5 days. acute, rapid progression, serious, life threatening.
what is the poster child for CNS viruses? where does it tend to localize? what damage does it cause?
HSV encephalitis. likes the temporal lobe. hemorrhagic and necrotic. can cause edema –> transtentorial herniation.
on histology, lymphocytic infiltrate that goes from vessels to neural parenchyma indicates what kind of problem?
virus (rather than bacteria or infarction)
classic histologic sign for viral encephalitis?
lymphocytic inflammatory response, death of neurons/glial cells, perivascular lymphocyte cuffs, microglial nodules, may see inclusion bodies.
what is a microglial nodule/cluster? what does it indicate?
site where neuron has died, been eaten by microglial cells via neuronophagia. indicates viral disease.
inclusion bodies in nuclei indicate what kind of problem?
viral until proven otherwise.
viral infection: what will CSF show?
elevated WBCs (usually lymphocytes), elevated protein, normal glucose.
for what disease is the CNS its second target organ?
HIV.
what are some of the diffuse CNS functions affected by HIV?
multiple mental functions are impaired: attention, motor, visual recog, verbal learning.
how does localization of the CNS area affected help in diagnosing viral infection?
each virus has a favorite location to invade.
what is the AIDS-dementia complex?
subacute dementia. HIV infects cells in the brain which produce toxins, which damage/kill neurons and oligos.
histologically, what would a slide of a patient with HIV-encephalitis look like?
microglial nodule: typically around blood vessels. population of macrophages/monocytes
HIV-encephalitis: the perivascular giant cells can produce what? leads to what problems?
produce inflammatory cytokines, leads to diffuse inflammation of the brain parenchyma.
HIV: why is it so hard to get/abolish at all the HIV+ cells in a patient?
Perivascular cells will stay in CNS for a few months, then circulate through body spreading virus. Due to BBB, most treatments don’t access these cells
what are the 4 most important AIDS associated diseases?
Toxoplasma gondii
Cryptococcal meningitis
Progressive multifocal leucoencephalopathy
B cell lymphoma
what happens if you have had mono, and your immune system becomes very compromised?
you hae epstein-barr virus which your immune system can normally keep under control. with immunosuppression, EBV gets to CNS and turns into lymphomas. tumors deep in brain, small, many.
what does PML stand for?
Progressive Multifocal Leukencephalopathy
what is the cause of PML? how do people get it?
JC Virus (type of papova virus, DS DNA). up to 20% of us have JC virus, but won’t know it unless we get immunosuppressed.
where does the JC virus live within the body?
oligo cells and renal tubule cells
unpack the meaning of PML
P: progressive. evolves over weeks to months.
M: multifocal. sites all over the brain tissue. starts with small lesions, then these foci continue to grow and coalesce.
L: leukoencephlo[athy. white matter related. makes sense given that target cell is oligos, which make myelin in the white matter.
PML: histologic appearance?
extensive myelin loss seen with myelin stain.
generally, white matter becomes tan/gliotic.
infected oligodendroglia will hypertrophy because virus has taken over machinery, making tons more virus.
JC infected oligodendroglia: appearance on histology?
packed with tiny virus particles. each will eventually be released and infect other oligos.
what is toxoplasmosis?
intracellular parasite
what animal carries toxoplasmosis?
cats, mainly, and rodents, pigs then humans.
what can toxoplasmosis cause?
usually mild flu, not problematic. but if preg woman, these parasites can cross the placenta and destroy the fetal brain. intracranial calfication in baby brain.
gross brain appearance of toxoplasmosis?
necrotizing lesions in deep structures of the brain. typically hemorrhagic
histologic appearance of toxoplasmosis?
tiny granulated bits of material in cell (pseudocyst), each being a toxo tachyzoite capable of spreading infection. Not much inflammation due to immunosuppression.
CSF findings with a classic subdural empyema?
high neutrophils (typically caused by bacteria)
high protein
low sugar
can culture and stain bacteria
gross appearance of a cranial subdural empyema?
white pus-like material below dura
causative agents in bacterial meningitis: most common for infants?
group B strep, E coli, Listeria
causative agents in bacterial meningitis: most common for 2months -5yrs?
hemophilus, pneumococcus, meningococcus, M tuberculosis
causative agents in bacterial meningitis: most common for adults?
pneumococcus, meningococcus, (M tuberculosis)
causative agents in bacterial meningitis: most common for elderly?
Listeria, pneumococcus
what is the mechanism of neonatal meningitis?
can get Group B strep at time of birth if mom is infected. (vaginal commensal). will see subarachnoid space filled with pus.
gross appearance of bacterial meningitis?
congested/dilated blood vessels, pus beneath the leptomeninges and along vessels, brain swelling. pus does not invade parenchyma
how can bacterial meningitis affect the parenchyma?
pus does not invade parenchyma, but the inflammation in the subarach space causes release of inflammatory cytokines, causing brain tissue to become edematous and distend –> herniation –> death.
what is the timeframe for a post-meningitis infarct? what is the cause?
after patient has been treated with abx and gone home. due to proteins/fragments of dead bacteria that still need to be cleared. a few diffuse into vessels, neutrophils arrive and destroy the vessel walls –> infarction.
what type of a reaction results from bacterial meningitis that has been treated but then pt presents with inflamed/damaged blood vessel walls?
Type III hypersensitivity.
what is the worst of the bacterial meningitis agents?
meningococcus.
another possible sequela of bacterial meningitis?
vascular damage -> infarct. also, fibrosis causing foramina to close, CSF builds up, ventricle becomes distended, hydrocephalus. can be fatal.
Tuberculosis causes what type of pathology to the CNS? does it evolve slowly or quickly?
causes scarring, collagen deposition. NOT pus. also causes entrapped blood vessels and ultimately multiple small infarcts.
evolves slowly, perhaps over months. neuro deficits will slowly evolve as well
mycobacterium: what does it cause? where does it live?
TB. lives in macrophages.
CNS TB: what happens to meninges and vessels?
fibrotic meninges, blood vessels are entrapped and become reactive to the point of occluding their lumina
if TB gets into the parenchyma, what can it cause? what kinds of sx?
can cause a tuberculoma (fibrotic mass of devitalized tissue). tumor-like problems. surgical problem.
brain abscess: clinical s/s? CSF?
headaches, ICP. CSF normal because this process doesn’t access the CSF (parenchyma only). these are masses that act like tumors. see edema, compression of gyri.
brain abscess: appearance on imaging?
ring enhancement, necrotic. can be single or multiple locations.
what bacteria are most likely to cause brain abscess? gram status?
strep muelleri, staph aureus.
gram + cocci
wwhat is the only condition where the brain will wall off part of itself using collagen/fibrous tissue?
brain abscess!
timeline of cellular response to a brain abscess?
microglia, neutrophils (digest parenchyma), macrophages (mop up), B cells (antibodies to bacteria). then necrosis, then fibrosis within a few weeks.
what is ventricular pedal march?
brain abscesses will rupture at some point. pus and bacteria will spread to adjacent tissue as daughter abscesses towards ventricles. eventually will rupture into subarachnoid space and cause bacterial meningitis.
aspergillus. appearance histologically? will it affect immuno-competent people?
branching hyphae. will only affect immunosuppressed people.
candida. appearance histologically? will it affect immuno-competent people?
pseudo-hyphae. thin, wiry, no branching. will only affect immunosuppressed people.
cryptococcus: appearance histologically? will it affect immuno-competent people?
will affect both immunocompetent and immunosuppressed.
candida: appearance on gross brain?
area of ischemic necrosis into which the organism grows. sharp delineations. fungus balls. can be one big one or many tiny ones.
cryptococcus: people with what may get this? what does it do to the brain?
TB will often get this
causes diffuse meningeal inflammation. in parenchyma, diffuse inflammation and necrosis with mucus capsules (JELLY/MUCUS)
cryptococcus: appearance histologically?
mono-budding yeast. may have thick mucus capsule
aspergillus: initial clinical presentation?
usually goes to resp system first. necrotizing infection in lung, big fungus balls. then spreads to brain, other organs.
aspergillus: appearance of CNS infection?
huge areas of infection/hemorrhagic necrosis in the brain. may cause infarct then kill parenchyma as it advances. feeds on dead brain tissue. huge lesions.
aspergillus: how does it get from lungs to CNS?
via blood: will cause small clots, then enter parenchyma when micro-embolus causes damage to vessel wall.
aspergillus: buzzword for histo appearance?
septate hyphae with 45’ branching
coccidioidomycosis: endemic where?
southwest area. aka valley fever. lives in the soil.
coccidioidomycosis: what pathology will it cause to the brain? in what % of patients does it cause dissiminated disease?
can cause basilar meningitis. causes flu like sx in lots of patients, but only disseminated dz in 1%
coccidioidomycosis: appearance histologically?
ROUND. bubbles.
cysticercosis: where does the organism come from?
larval form of the pork tapeworm Taenia soleum
cysticercosis: endemic where? causes what?
central america, mexico. can cause seizures, intracranial mass
cysticercosis: biggest problem?
if larva alive, problem is the masses
if the larva dies, you have an even bigger problem: inflammatory rxn, abscess, dissolving of brain tissue.
