Intro to Meningitis and Encephalitis (not finished)

Question 1

Meningitis develops in …

Answer 1

subarachnoid space, which lacks antibody and complement production required for phagocytosis

Question 2

clinical symptoms of meningitis

Answer 2

Fever (older individuals less likely) and headache

Nuchal rigidity, photophobia, rash, upper respiratory symptoms
Anorexia, nausea, and vomiting

Seizures, altered mental status

Question 3

Aseptic Meningitis Syndrome

Answer 3

often Viral but could be noninfectious

Fever, headache, and photophobia
less neck stiffness and altered mental status

Incidence highest during first year of life

CSF increase in lymphocytes and monocytes, slight increase in protein, and normal glucose.

PCR confirmation- not necessary.

Supportive therapy and recover on their own, but can be fatal in neonatal period

85% of viral meningitis are associated with enteroviruses

Question 4

be able to distinguish viral, bacterial, and fungal lumbar puncture results

Answer 4

a

Question 5

Enterovirus/Picornavirus

Coxsackie, ECHO viruses, polio

Answer 5

summer and fall

“pico” for small, “rna”

Transmitted oral fecal or respiratory

Genome organization
Single stranded
(+) sense RNA

Capsid symmetry
Icosahedral

No Envelope (Naked)

Question 6

Septic Meningitis

Answer 6

Bacteria

Fever, stiff neck, irritability, and neurologic dysfunction.

Acute onset and progression than aseptic meningitis.

Meningeal inflammation associated with inflammatory exudate in the CSF containing many polymorphonuclear leukocytes, increased protein, and decreased glucose.

Life-threating and requires prompt empiric therapy prior to lumbar puncture.

Question 7

Bacterial meningitis treatment

Answer 7

Immediate empiric treatment with
Ceftriaxone (3rd gen cephalosporins)
3 hr delay leads to increase in 3 month fatality

Risk of other agents: vancomycin (MRSA, resistant strep), acyclovir (HSV), cefepime (Pseudomonas, AIDS), ampicillin (Listeria)

Prophylactic treatment of high risk exposure: household contacts and those exposed to oral secretions

Question 8

3rd gen cephalosporins:
ceftriaxone, cefotaxime
mechanism, spectrum, resistance, side effects

Answer 8

Good CNS penetration
Mechanism: Bind to penicillin binding proteins to inhibit cell-wall synthesis

Spectrum: Used for streptococci and more serious Gram- infections, Can cross blood brain barrier

Resistance: inactivation of the drug by beta-lactamases

Side effects:
Strong association with Clostridium difficile- associated diarrhea

Question 9

Bacterial meningitis across different age groups

Answer 9

a

Question 10

Development of bacterial meningitis byH. influenza type b, N. meningiditis, Strept. pneumonia

Answer 10

1.  Mucosal colonization at
       nasopharynx
2. Invasion and multiplication in bloodstream
3,4.  Cross blood brain barrier
	and egress into CSF
5. Release of inflammatory cytokines in CSF by astrocytes and microglia
6. Increased permeability of BBB
7.  Diapedesis of leukocytes into CSF
8.  Edema and increased 
	intracranial pressure
9.  Neuronal injury (cranial nerve VIII)

Question 11

virulence factors

Answer 11

Meningitis occurs when pathogen virulence factors overwhelm the host defense mechanisms
Neisseia and Haemophilus influenzae have a capsule, IgA protein, pili, endotoxin, and outer membrane proteins
streptococcus pneumoniae has just a capsule and IgA protein

Pili allow colonization of the nasopharynx
IgA protease cleaves IgA facilitating colonization of mucosa
Capsule composed of acidic polysaccharides protects from phagocytosis
by polymorphonuclear granulocytes.

Question 12

Lipopolysaccharide (LPS)/ Endotoxin

Answer 12

Endotoxin is shed from outer cell membrane of Gram negative bacteria
Neisseria meningitides structure slightly different called LOS, which mimics brain sphingolipids so recognized as self
LPS activates macrophages leading to release of NO(hypotension, Shock) and IL-1(fever), and can activate disseminated intravascular coagulation leading to purpuric skin rash.

Question 13

Neisseria meningiditis- Meningococcal meningitis

Answer 13

Gram negative, diplococcus

13 serogroups- vaccine covers 4 types

Virulence factors include pili, IgA protease, capsule, and endotoxin

Outbreaks in late winter or early spring and are associated with overcrowding (dorms).

Transmit through respiratory droplets

LOS leads to thrombocytopenia, which is associated with disseminate intravascular coagulation leading to hemorrhagic skin rash.

Definitive and prophylactic treatment with ceftriaxone.