Microbiology of CNS infections Flashcards
1
Q
General concepts
A
- BBB (due to tight junctions btwn capillaries, choroid plexus, and arachnoid) prevents macromolecules and cells from entering the brain
- BBB also hampers the clearance of organisms once the BBB is penetrated
- Igs and immune cells are scarce in the brain except during infection, when the BBB breaks down
- During infections of the blood, large numbers of organisms are present and some rare variants are able to attack and enter the CNS
2
Q
Immune system and CNS
A
- Ab’s normally found in CSF are derived from serum, diffusion across BBB is size dependent (IgG/IgA>IgM)
- No lymphatics in CNS, very few phagocytic cells or complement in CNS
- During inflammation/trauma Ab’s leak into CSF and immune cells can move into CSF
- PMNs are dominant inflammatory cells in acute bacterial infections of CNS
- Mononuclear cells are dominant response to viral (T cells mostly) infections and subacute infections (TB and fungal) of the CNS
3
Q
Cellular structure
A
- No brain-CSF barrier, cellular gap btwn neurons is 10-15nm, so free movement of pathogens in CNS is restricted
- Surface receptors on CNS cells required for viral entry
- Toxins and virus can be carried by axoplasmic transport (along axons to cell body)
- Tetanus toxin is sequestered in vesicles at peripheral axon terminal
- Rabies virus also moved along axon
- Staph and enterobacters can directly enter CNS due to craniotomy and skull fractures, or spread from an adjacent sinus via surgical shunts or congenital defects
- Hematogenous spread is most common way of infecting CNS (rare variants in blood attack CNS)
4
Q
Meningitis
A
- A diffuse infection by bacteria, fungi, or viruses resulting in inflammation of pia-arachnoid meninges
- Infants are particularly sensitive, younger than 28 days is usually E coli, group B strep, or listeria
- Neonates represent less than 10% of meningitis cases but 50% of meningitis mortality
- Adult bacterial meningitis is mostly neisseria meningitidis and strep pneumonia (unless there is penetrating wound to skull or IC host)
5
Q
Acute vs Subacute meningitis
A
- Acute meningitis due to bacteria or viruses
- Viral meningitis more frequent than bacterial, but tends to be benign and seasonal
- Subacute meningitis includes TB and fungi
- Usually the fungus is cryptococcus, which can infect both immunocompetent and immunocompromised hosts
- Coccidioides and other fungi can also cause subacute meningitis
6
Q
Pathogenesis
A
- Most pathogens invade CNS from the blood, risk of CNS infection depends on magnitude of blood infection
- Pathogens in blood normally cleared by reticuloendothelial system, speed of removal being proportional to size (bigger the faster its cleared)
- Bacteria that have capsules or intracellular bacteria can escape phagocytosis
- Enteroviruses and arboviruses can escape clearance due to their small size
- Some viruses infect endothelial or choroid epithelial cells and then enter CNS
7
Q
Clinical manifestations of meningitis
A
- Primary symptoms (non-descript): headache, feaver
- Descriptive symptoms: nuchal (neck) rgidity (stiffness during forward flexion), brudzinski sign (neck stiffness causing reflex flexion of the legs) and kernig sign (limited extension of leg when flexed at knee)
- May cause reduced consciousness, seizures
- Purulent material collects around base of the brain, may cause cranial nerve palsies, obstruct CSF flow (hydrocephalus)
- Vasculitis develops, causing infarcts and mulitfocal neurological deficits
- Untreated is uniformly fatal
8
Q
Other possible manifestations of meningitis
A
- Rash of enterovirus infections
- Parotitis of mumps
- Multiple petechiae of meningococcemia
9
Q
CSF examination
A
- Acute bacterial meningitis evokes a PMN response in CSF and substantially reduces CSF sugar content
- Protein builds up rapidly in CSF w/ acute bacterial meningitis
- In subacte fungal meningitis inflammatory response is mostly mononuclear cells, CSF sugar reduction is slower, protein levels elevated (may be slightly)
- Viruses produce a mononuclear response, CSF protein may be elevated (possibly only slightly), but sugar is usually normal (may be slightly reduced)
10
Q
Rx of meningitis
A
- Must use agents that pass the BBB, use CDC guidelines
- Mortality of acute bacterial meningitis even w/ Rx is 15%
- Sequelae frequent in survivors
- Viral meningitis usually only requires Sx Rx since the disease is self-limiting
11
Q
Abscesses
A
- Brain abscesses develop from a contiguous focus of infection, or by hematogenous spread from a distant focus (lung, heart)
- Many abscesses have mixed flora of aerobic and anaerobic bacteria
- Most are due to bacterial seeding of already devitalized (dead) tissue
12
Q
Clinical manifestations of abscesses
A
- Primary manifestations are headache, focal signs, and seizures, often w/o fever
- Signs may be insidious
- CT and MRI should be performed, abscesses are ID’d by a hypo-dense region representing pus surrounded by an enhancing region representing neovascularization and edema around the fibrous abscess wall
- CSF usually sterile, must culture the abscess cavity
13
Q
Rx of CNS abscesses
A
- Must Rx with multiple antibiotics to cover multiple common organisms
- If encapsulated then it must be drained to prevent rupture into brain
- Spinal epidural and all subdural abscesses are emergencies, as spinal abscesses can lead to paralysis and anesthesia at and below the level of abscess
14
Q
Encephalitis
A
- An inflammation of the brain parenchyma usually due to viruses that produce wide-spread intracellular infections
- Life-threatening encephalitis usually due to herpes simplex viruses and arboviruses
- Pathogenesis: usually occurs first w/ systemic infection, either from new infection or recurrent latent infection
- Often localized to frontal and temporal lobes, infecting neurons and glial cells
- Rabies can be spread thru axons (entering from DRGs/spinal nerves)
15
Q
Clinical manifestations of encephalitis
A
- HSV encephalitis in the non-neonate: focal signs evolve over 1-2 weeks including headache, fever, hallucinations, bizarre behavior, hemiparesis, aphasia
- CSF may show no response of PMNs, but usually shows mononuclear cells
- CSF protein is usually elevated and sugar usually normal
- Can find IgM in CSF
- EEG and CT used to Dx
