1
Q
Difference between viral and bacterial meningitis
A
Viral is usually mild and self-resolving,
bacterial can be life-threatening.
VIRAL IS MORE COMMON
2
Q
Bacterial meningitis CSF findings
A
low glucose high protein (from breakdown of BBB) high WBC (with high neutrophils)
3
Q
Sx of viral meningitis patients
A
- not extremely ill or encephalopathic
- fever/malaise
- headache
- neck stiffness
- low back pain
4
Q
Causes of viral meningitis
A
enterovirus (80%) - includes Echo, Coxsackie, Enterovirus 71
Mumps - 10%
Recurrent aseptic meningitis - HSV2, HIV, VZV
5
Q
Causes of viral encephalitis
A
30% arborvirus, via mosquitos, elderly/young
23% enterovirus, via GI/URI infx
27% HSV1, temporal lobe, acyclovir
6
Q
Differential for viral encephalitis
A
bac meningitis fulminant TB RMSF, Lyme Dz brain abscess bacterial endocarditis CNS vasculitis
7
Q
HSV encephalitis
A
- rare, usually reactivation of latent (can be acute too)
- targets temporal lobe
- causes necrosis, will see RBC in CSF
- dx by PCR
- 70% mortality without tx
8
Q
Flaviriae family
A
Flaviviridae - SLE, West Nile, JEV
Pestiviruses - cow, pig, sheep
HCV
9
Q
St. Louis encephalitis
A
- caused by flavirvirus
- causes: febrile HA, aseptic meningitis, encephalitis
- incubation period 4-21d
- 50% dead in 1 week, 80% dead in 2 weeks
- no vaccine/antiviral
10
Q
West Nile Virus
A
- caused by flavivirus
- from bird, localizes in salivary glands of mosquitos
- humans are incidental hosts
- most infx are mild w. febrile HA, myalgia, skin rash, swollen lymph glands
- rarely serious, but no vaccine/antivirals
11
Q
Togaviridae
A
Rubivirus - rubella, limited host range
ALphavirus - WEE, EEE, VEE
- Dz varies based on dose and host
- initially replicates in muscle/fibroblasts, fever for 2 weeks and may b/c encephalitis
- no vaccine (except for horse/labworker)
12
Q
Bunyaviridae include
A
California encephalitis virus
La Crosse encephalitis virus
13
Q
Replication fo Bunyaviridae
A
similar to RNA- viruses except genes are found on 2-3 separate RNA segments, replication occurs only in cytoplasm (vs. influenza)
14
Q
Most common cause of arboviral induced pediatric encephalitis in the US
A
La Crosse virus
15
Q
Rhabdoviridae include
A
vesiculoviruses - vesicular stomatitis
lyssaviruses - cause rabies
bullet shaped
16
Q
Rabies
A
- caused by lyssavirus
- replication limited to neuronal cells, but concentration is high in salivary glands during final stages of dz
- uniformly fatal if no tx
- long incubation 2-3 months (why vaccine works)
- bite –> enters muscle via pH dependent post endocytosis –> replicates locally –> through peripheral sensory nerves –> travels up spinal cord
- prefs limbic system, midbrain, hypothalamus
- prodromal: 2-10 days post bite, abnormal sensation around bite
- acute neurologic phase: furious rabies, paralytic/dumb, hydrophobia
- coma phase: 2-7 days post neurologic, death via respiratory arrest
- vaccine is inactivated virus, Human Rabies Ig at site of wound
17
Q
Arenaviridae includes
A
Lymphocytic choriomeningitis virus (LCMV)
18
Q
Neuro complications and AIDS
A
- affects 40% of AIDS pts
- opportunistics: toxoplasmosis is most frequent, also crytococcal TB, JC (PML), CMV
- cancer: CNS lymphoma, mets of Kaposis
19
Q
What is ambisense replication an who has it?
A
LCMV…has 2 RNA segments for 2 proteins, has host cell ribosomes
- genome is used a template for transcription of NP and L mRNAs –> polymerase makes an anti genome for each segment –> + sense anti genome used to make a gp mRNA –> virus particles assembled and released by budding
20
Q
Mosquito vector viruses
A
Flavi
Toga
Bunya
21
Q
Animal vector viruses
A
Rhabdo
Arena
22
Q
Arenaviridae transmission and dz
A
- enter via pH dependent post endocytosis
- ambisense replication strategy
- transmitted via inhalation of aerosolized virus from rodent excreta/saliva
- rarely fatal, usually an initial phase with fever/HA/NV (primary viremia) and aseptic meningitis phase 10 days later with sudden onset of deafness
- no vaccines
- antiviral: Ribavirin
23
Q
Picornavirus
A
- nonsegmented ssRNA+
- polio, coxsackie, echo
- mild febrile to aseptic meningitis
- vaccine only for Polio
- antiviral: Ribavirin
24
Q
Paramyxovirus
A
- nonsegmented ssRNA-
- causes measles and mumps
- MMR vaccine
- no antiviral
25
Herpesvirus
- linear dsDNA virus
- HSV1/2, VZV, CMV, EBV
- causes encephalitis
- No vaccine
- antiviral: acyclovir, ganciclovir, foscarnet
26
Bacterial meningitis pathogens for neonates (<3mo)
GBS
G- enterics
Listeria
27
Bacterial meningitis pathogens for 3mo - 2yo
S. Pneumo
Neisseria
H.I.B
28
Bacterial meningitis pathogens for 2yo-18yo
S. Pneumo
| Neisseria
29
Work up for bac meningitis
Gram stain of CSF --> Rapid agglutination for capsule --> PCR --> Culture CSF/blood
30
S. Pneumo
- MCC of bac meningitis in US
- capsulated, IgA Protease, Lancet Shaped
- risk fx: splenic dysfunction, skull fracture/anatomic defect/cochlear implant, recurrent otitis media/AIDS
- tx: Cephalosporin, Vancomycin (sometimes give Dex BEFORE)
- 2 vaccines: Pneumovax and Prevnar
31
Pneumovax
- multivalent nonconjugated vaccine for S Pneumo
- for high risk groups: >65yo, HIV, asplenia, transplant
- protects against invasive pneumococcal dz
- lasts 5-7 years, except in infants
32
Prevnar
- heptavalent conjugated vaccine for S. Pneumo
- conjugated = anamnestic (memory)
- generates Abs in kids as young as 2mo
33
Neisseria Meningitides
- 2nd MC bac meningitis (types B and C in the U.S.)
- crowded areas, alcoholics, C6 deficiency
- has capsule, LPS
- transmitted via droplets, nasopharynx
- rapid progression b/c endotoxin,
- disseminated infx: petechial rash
- Tx: penicillin G + ceftriaxone + Dex (b4)
- Prophylaxis: ciprofloxacin
- 2 vaccines
34
Menomune
- old capsular vaccine for N. Meningitides
- A, C, Y, V135
- for military groups and thigh risk
35
Menactra
- new conjugated vaccine for N. Meningitides
- A, C, Y, V135
- recommended for all kids 11-12yo
- conjugated to diptheria
36
H. Flu
- MC bac meningitis in 6mo-5yo
- Type B is the only capsulated strain and the only one that causes invasive dz
- untyped = unencapsulated version causes otitis media
- arthritis, epiglottitis, meningitis, osteomyelitis, pneumonia
- gram stain needs CAP (not BAP) and factors V ( NAD/NADP) and factor X (Hemin)
- conjugated type b vaccine (conjugated w diptheria) part of standard infant/childhood vaccines
- tx: dex + 3rd gen ceph
37
Listeria
- causes bac meningitis
- esp bad for pregnant women
- G- bacillus
- facultative intracellualr parasite
- foodborne via unpasteurized cheese, hot dogs, deli meats
- GI/GU, also found in genital tract, neonatal infx
- pathogen: infects epithelial cells and monocytes/macrophages, colonize actin and move around cell and stay hidden from immune system
- flu like in normal adults, can cause bacteremia, meningitis in IC and neonates
38
Exerohilium rostratum
- steroid associated fungus that causes meningitis in healthy individuals (common black mold)
- incubates 20 days
- culture CSF and send to CDC for PCR
- Tx: IV voriconazole for meningitis and amphotericin B for severe cases (both for 3 months)
39
Cryptococcus neoformans
- MC fungal meningitis
- inhaled via pigeon poop, causes meningitis in AIDS patients
- inhaled, hematogenous spread, initial infx is asymptomatic pulmonary infx
- chronic dz: meningitis with soap lesions in the brain, causes inc. ICP
- Dx: yeast with halos in India Ink
- Tx: amphotericin and flucytosine
40
Cryptococcus gatti
fungus found in trees in Australia that can cause meningitis in healthy individuals
41
Family Papovaviridae includes
Papilloma subfamily
Polyoma virus
Vacuolating Virus (Sv40 - monkey)
42
Polyoma virus
- circular ds DNA virus around histone
- BK and JC viruses which are ubiquitous
- only a problem in AIDS and transplant pts
- transpalnt pts 90% fatality in 6 mo
- AIDS pts changing HAART reduces fatality to 50%
43
Polyoma virus pathogenesis
- human cells are permissive and allow virus growth in the nucleus and release of virion by lysis (non permissive cells are transformed)
- virulence factors include early 3 T Ag's (small/large immortalize cell and middle/small transform cell) and late structural proteins
- initial replication in GI or respiratory tract and secondary spread to kidney/lung/brain (kidneys are persistently infected)
- can cause PML
44
PML
- Progressive Multifocal Leukoencephalopathy (PML)
- caused by reactivated JC virus (a polyoma)
- infects oligodendrocytes and demyelinates them
- Sx: AIDS + clumsiness + progressive weakness + speech changes
- Dx: PCR amplification for JC virus DNA (w. prove) from CSF/brain biopsy
45
Polio epidemiology
- nonenveloped icosahedral capsid, ssRNA+
- currently in Afghanistan, Pakistan, Nigeria
- infx in kids < 5yo, adult infx = delayed exposure to virus from inc. sanitation
- only cases in Western world were due to revertant oral vaccine
46
Polio transmission
- causes Poliomyelitis ~ Flaccid paralysis
- spread fecal-oral in the summer
- humans are the only reservoir
47
Polio dz process
- incubates 7-14 days
- initial replication is pharynx and GI
- viremia --> enters BBB --> destroys motor neurons during replication
48
Polio dz manifestation
- mostly subclinical but 3 forms exist
1. Abortive Poliomyelitis: nonspecific febrile illness 2-3 days with no CNS involvement
2. Aseptic Meningitis (Nonparalytic Poliomyelitis): febrile illness + stiff neck with limited CNS infx
3. Paralytic Poliomyelitis: febrile illness --> lapse of sx --> flaccid paralysis +/- attack all limbs or brainstem. Gradual recovery in 6 mo with permanent lingering paralysis (5% fatality rate) and Post-Polio syndrome with inc. weakness forever
49
Polio diagnosis
Early rectal, throat, stool swabs
Later CSF
Vaccine components distinguished from wild virus via strain-specific polyclonal sera
50
Polio Salk
- Polio vaccine IPV = formalin inactivation
- prevents reversion
- protects against paralysis but not spread
- 3 subQ injections + booster
- CDC recommended for U.S.
51
Polio Sabin
- Polio vaccine OPV = live oral vaccine
- live oral vaccine so possible reversion
- oral and cheap
- protects against paralysis AND spread
- CDC recommended for global
52
TSE
- transmissible spongiform encephalopathy
- caused by prions, infectious proteins
- looooong incubation period
- spongiform change, gliosis, amyloid plaque, neuronal loss
- Dz: Kuru, CJD, GSS, FFI, varian CJD, scrapie
53
Scrapie
- subacute ataxia of sheep/goat
- 1 y/o: infx of alimentary tract (lymphatic/intesting)
- 2 y/o: infx of brain
- 3 y/o: spongiform change and clinical dz
54
Kuru
TSE - tremble with fear
| - caused by cannibalism EW
55
Prion
- infectious protein capable of causing TSE
| - extremely resistant to things that damage nucleic acids/viruses (radiation, nucleases, proteases, EtOH)
56
Prion Theory
- increase in conserved prion protein on Chr 20 in neurons and lymphocytes
- PrPC: normal cellular form of surface gp, reduces Abeta plaques via dec. BACE1 activity
- PrPSC: dz form that can occur via sporadic/familial mutation or via infx
- C vs. SC: difference between PrPsc is different folding (same AA sequence) so it b/c resistant to proteases and causes inc. in intracellular aggregates and dec. stability
57
How do PrP-Sc form?
- P* intermediate form
- PrP-Sc acts as template for P* causing it to fold into Sc form (so template predicts final conformation here, NOT AA SEQUENCE)
- chain reaction happens
58
CJD
- MC TSE
- akinetic mutism, cerebellar dysfunction, dementia, clonus
1. sporadic: 60yo, bad prognosis, specific EEG
2. iatrogenic: hGH from pituitary graft > corneal/dural grafts, NOT transmitted through blood
3. familial: AD mutation in prion protein, 45-50 yo w. 2-4 yr survival
- Dx: spongiform change, lack of A beta plaques, CSF to rule out tertiary syphillis and measles
59
vCJD
- Mad Cow Dz
- contaminated beef and blood transfusion
- more contagious than reg CJD
- AD w. homzygous methionine @ codon 129
- 29yo w. 14 mo survival + anxiety, depression, sensory (visual/akinetic mutism)
- Dx: atypical EEG + prion + tonsilar biopsy + florid plaques + spongiform basal ganglia
60
Gerstmann Straussler Scheinker Dz
- AD mutation in codon 102 of prion protein
- 48yo w. 5 yr prognosis
- gait/ataxia changes > dementia
- atypical EEG
- inc. A beta plaques (vs. CJD)
61
Familial Fatal Insomnia
- AD mutation in codon 129/178
- Age 49 w. 13 mo prognosis + insomnia + ANS probz
- inc. neuronal loss but dec. spongiform change and less A beta plaques
62
MC acute encephalitis
Herpes encephalitis
Neuro 2
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