L36- Nervous System and Special Senses Infections I

Question 1

list the common pathways of microbes for CNS infections

-also list the infrequent pathways

Answer 1

• blood / hematogenous
• peripheral nerves
• adjacent bone, adjacent sinus
• anatomical defects: congenital, surgical, traumatic

Infrequently: BBB, BCSFB (blood-CSF barrier)

Question 2

define the following:

• (1) meningitis
• (2) encephalitis
• (3) meningoencephalitis
• (4) ependymitis
• (5) choroid plexitis

Answer 2

1- inflammation of meninges (brain, spinal cord)
2- inflammation of brain parenchyma
3- inflammation of meninges and brain parenchyma

4- inflammation of ventricular walls
5- inflammation affecting choroid plexus

Question 3

define the following:

• (1) empyemas
• (2) cerebritis
• (3) myelitis

Answer 3

1- subdural empyema, caused by infection + collection of focal purulent material in space between dura and arachnoid

2- inflammation of cerebrum ==> abscess

3- inflammation of spinal cord

Question 4

define the following:

• (1) ADEs

- (2) spongiform encephalopathies

Answer 4

1- acute disseminated encephalomyelitis: post-encephalitis with attack to myelin

2- prion diseases OR transmissible spongiform encephalopathies (TSEs) = family of rare progressive neurodegenerative disorders (affects humans and animals)

Question 5

list the common examples of septic meningitis

Answer 5

• **Strep. pneumoniae
• N. meningitidis
• H. influenzae
• S. aureus
• CoN Staph. (coagulase neg.)
• Gram neg. bacilli
• listeria monocytogenes

Question 6

list the common examples of aseptic meningitis

Answer 6

Tb

Non-Tb:

• spirochetes (bacteria)
• cryptococcus (fungal)
• enteroviruses, arboviruses (viral)
• toxoplasma gondii (parasite)

Question 7

describe the timeline classification of meningitis (acute, subacute, chronic)

Answer 7

Acute <24hrs
Subacute <7 days
Chronic >4wks

Question 8

describe the general timeline for meningitis based on etiology / infections type- order from rapid to slow onset

Answer 8

Acute:

• Virus: hrs - 1day
• Aerobic Bacteria: hrs - few days

Chronic:

• Anaerobic Bacteria, Tb, Fungi: days - wks
• Parasites, Syphilis: wks - yrs
• Prions: yrs

Question 9

Meningitis:

• mostly seen in (1) age group
• (2) are the hallmark Sxs
• (3) are the many other possible Sxs
• (4) is unique to meningococcal infections

Answer 9

1- children, elderly

2- fever (sudden rise), neck stiffness / nuchal rigidity (often not in children), heavy HA

3:

• n/v
• seizures (minimal), painful photophobia / phonophobia
• loss of concentration / confusion (minimal)
• sleepiness / difficult awakening
• lack of appetite, insatiable thirst

4- rashes: flat, purple, constant

Question 10

Meningitis:

• (1) Triad of Sxs, seen in (2)% of pts
• (3) describe the physical exam signs

Answer 10

1- HA, fever, neck stiffness (often not in children)
2- 85% pts

3:

• Nuchal Rigidity: resistant passive flexion
• Kernig’s Extension: slow extension of knee with thigh flexed –> pain, neck flexion
• Brudzinsky’s sign: flexion of neck causes hip flexion

Question 11

Meningitis Tests:
______ = flexion of neck causes hip flexion

______ = slow extension of knee with thigh flexed illicits pain and neck flexion

Answer 11

1- Brudzinsky’s sign

2- Kernig’s Extension

Question 12

Meningitis Diagnosis:
-Imaging is always performed in patients presenting with the following, (1), before (2) is performed

• (3) are the initial studies
• (4) are additional CSF studies
• (5) are the pathogen specific studies

Answer 12

1- dec consciousness, seizures, immuno-compromised, focal neurological deficits (want to avoid herniations)
2- Lumbar Puncture

3- CSF: opening pressure (LP => ICP), glucose content, protein content, cell count, Gram stain and culture (note HSV PCR is often tested since #1 cause)

4- CSF: serology for arboviruses (no PCR); note peak viremia occurs before onset of Sxs

5- pathogen specific PCR

Question 13

list the causes of bacterial meningitis (septic) by age group

Answer 13

Neonates: *group B Strep., E. coli K1, Strep. pneumoniae, Listeria monocytogenes (vertical transmission)

Infants / Children: S. pneumoniae, N. meningitidis, H. influenzae type B (Hib), group B Strep.

Teens / Young adults: N. meningitidis, S. pneumoniae

Older adults: S. pneumoniae, N. meningitidis, Hib, group B Strep.. L. monocytogenes

Question 14

list the bacterial causes of septic meningitis that have vaccines

Answer 14

• N. meningitidis (type A, C – not B)
• H. influenzae type B (Hib) — <1y/o
• Strep. pneumoniae — pneumovax 23 (older adults or susceptible individuals)

Note- vaccine based on capsule

Question 15

describe the important shared virulence factors for meningitis among the following:

• N. meningitidis
• H. influenzae
• S. pneumoniae

Answer 15

• N. menigitidis: capsule, IgA protease, pili, endotoxin (LOS)
• H. influenzae: capsule, IgA protease, pili, endotoxin (LOS)
• S. pneumoniae: capsule, IgA protease

Question 16

LPs are taken from the ______ intervertebral spaces

Answer 16

Adults: between L3/L4, L4/L5

Question 17

CSF findings for bacterial meningitis (indicate elevated, normal, depressed where indicated):

• (1) appearance
• (2) opening pressure
• (3) WBC count (and type)
• (4) protein
• (5) glucose

Answer 17

1- cloudy
2- elevated
3- elevated, >80% PMNs
4- elevated
5- depressed

Question 18

CSF findings for viral meningitis (indicate elevated, normal, depressed where indicated):

• (1) appearance
• (2) opening pressure
• (3) WBC count (and type)
• (4) protein
• (5) glucose

Answer 18

1- clear
2- n/a
3- elevated, >50% lymphocytes, <20% PMNs
4- elevated
5- slightly depressed to normal

Question 19

CSF findings for fungal meningitis (indicate elevated, normal, depressed where indicated):

• (1) appearance
• (2) opening pressure
• (3) WBC count (and type)
• (4) protein
• (5) glucose

Answer 19

1- cloudy
2- elevated
3- elevated, >50% lymphocytes
4- elevated
5- slightly depressed to normal

Question 20

CSF findings for Tb meningitis (indicate elevated, normal, depressed where indicated):

• (1) appearance
• (2) opening pressure
• (3) WBC count (and type)
• (4) protein
• (5) glucose

Answer 20

1- fibrin-web
2- n/a
3- elevated, >80% lymphocytes
4- elevated
5- depressed

Question 21

list the Ags tested for in CSF screening (note- not ordered routinely, explain)

Answer 21

Bacteria: S. pneumoiae, N. meningitidis, H. influenzae type B (Hib)

Fungal: cryptococcus neoformans

Note- low specificity, low sensitivity

Question 22

list the indications where imaging (CT/MRI) should be performed before Lumbar Puncture

Answer 22

• *papilledema
• *abnormal level of consciousness
• *immunocompromised state
• h/o CNS disease (mass lesion, stroke, focal infection)
• seizure w/in wk of presentation
• focal neurological deficits (dilated non-reactive pupil, gaze palsy, arm/leg drift)

Question 23

list the complications of bacterial meningitis (septic)

Answer 23

• seizures
• loss of hearing or vision
• irreversible brain damage
• hydrocephalus
• subdural effusion

-septic shock – DIC

Question 24

describe the highlight microbial features of N. meningitidis (gram stain, shape)

list relevant serotypes

Answer 24

(Neisseriaceae family)
Gram-, facultative intracellular diplococci

A (Africa), B (kids, not in vaccine), C, X, Y, Z, W135, L

Question 25

N. meningitidis culturing: - (1) sample sites - (2) describe agar(s) - (3) may used in co-agglutination systems for early identification - (4) may also be performed on (1) samples

Answer 25

1- blood, CSF --- must process quickly 2: (fastidious organism- must grow in blood) - (from sterile sites) Chocolate agar (Hemin / factor X, NAD / factor V) at 37C, 3-10% CO2 - Thayer-Martin (selective media) 3- Anti-capsular antisera 4- PCR

Question 26

N. meningitidis compared to N. gonnorrhea based on the following lab tests: - oxidase - glucose - maltose - sucrose

Answer 26

N. meningitidis: oxidase+, glucose+, *maltose+, sucrose- N. gonnorrhea: oxidase+, glucose+, *maltose-, sucrose- note- for sugars, yellow is positive and red is negative

Question 27

name the associated N. meningitidis virulence factors: - (1) allows for colonization and invasion of nasopharynx - (2) anti-phagocytic function - (3) endotoxin - (4) anti-complement (C3)

Answer 27

1- IgA protease (to cross mucosa) 2- capsular polysaccharide 3- Lipo-oligosaccharide, released in blebs 4- Factor H binding protein

Question 28

name the associated N. meningitidis virulence factors: - (1) outer membrane protein facilitating attachment - (2) outer membrane protein facilitating invasion - (3) outer membrane protein facilitating colonization and invasion

Answer 28

1- Opacity proteins (Opa, Opc) 2- PorA, PorB- produces pores 3- type IV pili/fimbria- also phase and antigenic variation

Question 29

list the important virulence factors for N. meningitidis

Answer 29

- type IV pili (colonization, invasion) - opacity proteins: Opa, Opc (attachment) - PorA, PorB (invasion) - lipo-oligosaccharide (endotoxin) - capsular polysaccharide (anti-phagocytic) - Factor H binding protein (anti-complement, C3) - IgA protease (colonization, invasion -- cross mucosa)

Question 30

briefly compare BBB to BCSFB

Answer 30

BBB: endothelium with tight junctions --> perivascular space --> astrocytic feet (glial limitans) BCSFB: normal endothelium --> stroma --> epitheium with tight junctions

Question 31

list the main CA causes of bacterial meningitis, include: - site of entry - age range - predisposing conditions

Answer 31

N. meningitidis: - nasopharynx - all ages - none predisposition, close quarters (dorms, daycare) is risk Strep. pneumoniae: - nasopharynx -- extension of skull fracture, distant foci - all ages - any and all conditions that predispose pneumococcal bacteremia

Question 32

list the main HA causes of bacterial meningitis, include: - site of entry - age range - predisposing conditions

Answer 32

S. aureus: - bacteremia, foreign body, skin - all ages - endocarditis, surgery, foreign body Gram- bacilli: - various entries - older adults and neonates - advanced illness, neurosurgery

Question 33

list the other common causes of bacterial meningitis that are not CA or HA associated (hint- 3), include: - site of entry - age range - predisposing conditions

Answer 33

Listeria monocytogenes: - GIT, placenta - older adults, neonates - defects in cell-mediated immunity Group B Strep. (agalactiae): - nasopharynx - older adults, neonates - post-partum H. influenzae: - nasopharynx - adults (unvaccinated infants, children) - diminished humoral immunity

Question 34

list the main risk factors for N. meningitidis

Answer 34

- nasopharynx carriers --- 10-20% of population - close quarters (military, dorms) -**Early (C3/properdin) and Late components of complement system

Question 35

N. meningitidis: - (1) transmission - (2) age group predominance - (3) season predominance

Answer 35

1- droplets, direct contact 2- children, teenagers 3- winter (Feb - Mar)

Question 36

N. meningitidis: - (1) USA serogroups - (2) serogroup is associated with large-scale epidemics

Answer 36

1- B (children), C, Y 2- A (Africa)

Question 37

N. meningitidis: - vaccine is based on (1) serogroups, compare both types - (2) is the other vaccine

Answer 37

1- A, C, W135, Y - conjugated <55 y/o - polysaccharide >2y/o 2- B capsule: similar to ICAM adhesion molecule --- vaccine in some other countries

Question 38

N. meningitidis clinical presentation: - (1) common Sxs - (2) common complication - (3) describe frequency of neurological Sxs

Answer 38

1- low BP, elevated pulse rate, diaphoresis + petechiae and ecchymoses 2- shock via DIC 3- seizures and other Sxs are less common than in other meningitis

Question 39

H. influenzae: - (1) classic microbial features - colonizes (2) usually - (3) is the major virulence factor and serotype

Answer 39

1- Gram- rod, oxidase+ 2- respiratory tract 3- capsule (strains a-f) --- type b is most invasive (polyribose phosphate capsule -- Hib)

Question 40

list the many H. influenzae meningitis risk factors

Answer 40

- *URI - *daycare - H. influenzae Otitis media - sinusitis, pharyngitis - cancer - pregnancy - older age - weakened immune system

Question 41

what is the goal of H. influenzae vaccine

Answer 41

give as early as possible to prevent colonization in nasopharynx

Question 42

GBS = (1): - (2) classic microbial features - commonly colonizes (3), therefore (4) are at high risk for infection

Answer 42

1- group B Strep., S. agalactiae 2- Gram+ cocci, β-hemolytic, bacitracin resistant 3- genital (10-30% women), GIT, URT (infants) 4- transferred during vaginal delivery

Question 43

Strep. agalactiae meningitis: - (1) serotypes - (2) onset of infection / incubation - (3) fatality rate

Answer 43

1- Ia, Ib, II, *III (most virulent, most common cause in neonates), V 2- early w/in 7 days OR late 7 days - 3 mos 3- 5-15%

Question 44

Strep. pneumoniae meningitis: - (1) classic microbial features - (2) describe prevalence - (3) vaccines

Answer 44

1- Gram+, α-hemolytic, diplococci-lancet shape, optochin sensitive 2- most common bacterial etiology of meningitis in adults of all ages and children >1mo 3- Prevnar 13 (<2y/o), Pneumovax 23 (<2y/o)

Question 45

Listeria monocytogenes meningitis: - (1) classic microbial features - (2) association in terms of transmission - (3) season prevalence

Answer 45

1- small Gram+ bacilli, tumbling motility, facultative anaerobe, β-hemolytic, grows at low T 2- food, placenta 3- summer months

Question 46

list the virulence factors of Listeria monocytogenes

Answer 46

- Internalin (InlA, InlB): adheres to cadherin in intestinal wall, allows invasion - Lysteriolysin O (LLO): to escape endosome into cytosol - Actin A motility (ActA): actin polymerization allows cell-to-cell transmission

Question 47

Listeria monocytogenes cause what syndromes in the following populations: - (1) healthy average adult - (2) pregnant women - (3) elderly person

Answer 47

1- cold Sxs 2- placenta invasion --> miscarriage 3- brain invasion --> death

Question 48

Listeria monocytogenes diagnosis: - (1) samples for culture - (2) hallmark result in LP - (3) is recommended in all pts with Listeria meningitis

Answer 48

1- CSF, blood 2- CSF with substantial Lymphocyte (>25%) elevation -- not PMNs 3- MRI with contrast due to inc ICP

Question 49

E. coli K1: - (1) classic microbial features - produces (2) - (3) transmission

Answer 49

1- Gram- bacilli 2- siderophore production (Fe sequesteration), endotoxin production 3- food, water, person-person