L36- Nervous System and Special Senses Infections I Flashcards
list the common pathways of microbes for CNS infections
-also list the infrequent pathways
- blood / hematogenous
- peripheral nerves
- adjacent bone, adjacent sinus
- anatomical defects: congenital, surgical, traumatic
Infrequently: BBB, BCSFB (blood-CSF barrier)
define the following:
- (1) meningitis
- (2) encephalitis
- (3) meningoencephalitis
- (4) ependymitis
- (5) choroid plexitis
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
define the following:
- (1) empyemas
- (2) cerebritis
- (3) myelitis
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
define the following:
- (1) ADEs
- (2) spongiform encephalopathies
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)
list the common examples of septic meningitis
- **Strep. pneumoniae
- N. meningitidis
- H. influenzae
- S. aureus
- CoN Staph. (coagulase neg.)
- Gram neg. bacilli
- listeria monocytogenes
list the common examples of aseptic meningitis
Tb
Non-Tb:
- spirochetes (bacteria)
- cryptococcus (fungal)
- enteroviruses, arboviruses (viral)
- toxoplasma gondii (parasite)
describe the timeline classification of meningitis (acute, subacute, chronic)
Acute <24hrs
Subacute <7 days
Chronic >4wks
describe the general timeline for meningitis based on etiology / infections type- order from rapid to slow onset
Acute:
- Virus: hrs - 1day
- Aerobic Bacteria: hrs - few days
Chronic:
- Anaerobic Bacteria, Tb, Fungi: days - wks
- Parasites, Syphilis: wks - yrs
- Prions: yrs
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
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
Meningitis:
- (1) Triad of Sxs, seen in (2)% of pts
- (3) describe the physical exam signs
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
Meningitis Tests:
______ = flexion of neck causes hip flexion
______ = slow extension of knee with thigh flexed illicits pain and neck flexion
1- Brudzinsky’s sign
2- Kernig’s Extension
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
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
list the causes of bacterial meningitis (septic) by age group
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
list the bacterial causes of septic meningitis that have vaccines
- 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
describe the important shared virulence factors for meningitis among the following:
- N. meningitidis
- H. influenzae
- S. pneumoniae
- N. menigitidis: capsule, IgA protease, pili, endotoxin (LOS)
- H. influenzae: capsule, IgA protease, pili, endotoxin (LOS)
- S. pneumoniae: capsule, IgA protease
LPs are taken from the ______ intervertebral spaces
Adults: between L3/L4, L4/L5
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
1- cloudy 2- elevated 3- elevated, >80% PMNs 4- elevated 5- depressed
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
1- clear 2- n/a 3- elevated, >50% lymphocytes, <20% PMNs 4- elevated 5- slightly depressed to normal
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
1- cloudy 2- elevated 3- elevated, >50% lymphocytes 4- elevated 5- slightly depressed to normal
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
1- fibrin-web 2- n/a 3- elevated, >80% lymphocytes 4- elevated 5- depressed
list the Ags tested for in CSF screening (note- not ordered routinely, explain)
Bacteria: S. pneumoiae, N. meningitidis, H. influenzae type B (Hib)
Fungal: cryptococcus neoformans
Note- low specificity, low sensitivity
list the indications where imaging (CT/MRI) should be performed before Lumbar Puncture
- *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)
list the complications of bacterial meningitis (septic)
- seizures
- loss of hearing or vision
- irreversible brain damage
- hydrocephalus
- subdural effusion
-septic shock – DIC
describe the highlight microbial features of N. meningitidis (gram stain, shape)
list relevant serotypes
(Neisseriaceae family)
Gram-, facultative intracellular diplococci
A (Africa), B (kids, not in vaccine), C, X, Y, Z, W135, L
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
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
N. meningitidis compared to N. gonnorrhea based on the following lab tests:
- oxidase
- glucose
- maltose
- sucrose
N. meningitidis: oxidase+, glucose+, *maltose+, sucrose-
N. gonnorrhea: oxidase+, glucose+, *maltose-, sucrose-
note- for sugars, yellow is positive and red is negative
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)
1- IgA protease (to cross mucosa)
2- capsular polysaccharide
3- Lipo-oligosaccharide, released in blebs
4- Factor H binding protein
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
1- Opacity proteins (Opa, Opc)
2- PorA, PorB- produces pores
3- type IV pili/fimbria- also phase and antigenic variation
list the important virulence factors for N. meningitidis
- 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)
briefly compare BBB to BCSFB
BBB: endothelium with tight junctions –> perivascular space –> astrocytic feet (glial limitans)
BCSFB: normal endothelium –> stroma –> epitheium with tight junctions
list the main CA causes of bacterial meningitis, include:
- site of entry
- age range
- predisposing conditions
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
list the main HA causes of bacterial meningitis, include:
- site of entry
- age range
- predisposing conditions
S. aureus:
- bacteremia, foreign body, skin
- all ages
- endocarditis, surgery, foreign body
Gram- bacilli:
- various entries
- older adults and neonates
- advanced illness, neurosurgery
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
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
list the main risk factors for N. meningitidis
- nasopharynx carriers — 10-20% of population
- close quarters (military, dorms)
-**Early (C3/properdin) and Late components of complement system
N. meningitidis:
- (1) transmission
- (2) age group predominance
- (3) season predominance
1- droplets, direct contact
2- children, teenagers
3- winter (Feb - Mar)
N. meningitidis:
- (1) USA serogroups
- (2) serogroup is associated with large-scale epidemics
1- B (children), C, Y
2- A (Africa)
N. meningitidis:
- vaccine is based on (1) serogroups, compare both types
- (2) is the other vaccine
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
N. meningitidis clinical presentation:
- (1) common Sxs
- (2) common complication
- (3) describe frequency of neurological Sxs
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
H. influenzae:
- (1) classic microbial features
- colonizes (2) usually
- (3) is the major virulence factor and serotype
1- Gram- rod, oxidase+
2- respiratory tract
3- capsule (strains a-f) — type b is most invasive (polyribose phosphate capsule – Hib)
list the many H. influenzae meningitis risk factors
- *URI
- *daycare
- H. influenzae Otitis media
- sinusitis, pharyngitis
- cancer
- pregnancy
- older age
- weakened immune system
what is the goal of H. influenzae vaccine
give as early as possible to prevent colonization in nasopharynx
GBS = (1):
- (2) classic microbial features
- commonly colonizes (3), therefore (4) are at high risk for infection
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
Strep. agalactiae meningitis:
- (1) serotypes
- (2) onset of infection / incubation
- (3) fatality rate
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%
Strep. pneumoniae meningitis:
- (1) classic microbial features
- (2) describe prevalence
- (3) vaccines
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)
Listeria monocytogenes meningitis:
- (1) classic microbial features
- (2) association in terms of transmission
- (3) season prevalence
1- small Gram+ bacilli, tumbling motility, facultative anaerobe, β-hemolytic, grows at low T
2- food, placenta
3- summer months
list the virulence factors of Listeria monocytogenes
- 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
Listeria monocytogenes cause what syndromes in the following populations:
- (1) healthy average adult
- (2) pregnant women
- (3) elderly person
1- cold Sxs
2- placenta invasion –> miscarriage
3- brain invasion –> death
Listeria monocytogenes diagnosis:
- (1) samples for culture
- (2) hallmark result in LP
- (3) is recommended in all pts with Listeria meningitis
1- CSF, blood
2- CSF with substantial Lymphocyte (>25%) elevation – not PMNs
3- MRI with contrast due to inc ICP
E. coli K1:
- (1) classic microbial features
- produces (2)
- (3) transmission
1- Gram- bacilli
2- siderophore production (Fe sequesteration), endotoxin production
3- food, water, person-person