Aseptic Meningitis& Encephalitis
Tania SorrellCIDM
May 2008
What is aseptic meningitis?
Viral meningitisEpidemiology
DiagnosisEmerging threats
Viral encephalitisEpidemiology
DiagnosisEmerging threats
Outline
Aseptic meningitis
Infective Non-infective
*Viruses *Drugs (adults>kids)Chronic s’dural
*Early bacterial Malignancy *Partially Rx’d bacterial Bechet’s disease*Parameningeal infection VasculitisL. monocytogenes SarcoidosisM. tuberculosis Congenital cystsSpirochaetes
C. neoformans Post-infectiousParasites, Rickettsiae Post-vaccination
Causes of meningism and a CSF mononuclear pleocytosis
Aetiology of viral meningitis
Enteroviruses >80% cases(polio, coxsackie, ECHO, EV)
Herpes viruses(HSV2>1, VZV, CMV, EBV, HHV-6)
Respiratory viruses(adenovirus, rhinovirus, influenza A & B)
Miscellaneous(HIV, arboviruses, mumps virus, lymphocytic choriomneingitis virus)
Enteroviruses by SerotypePolioviruses (PV) 3 serotypesCoxsackie A viruses (CVA) 23 serotypesCoxsackie B viruses (CVB) 6 serotypesEchoviruses (ECV) 28 /29serotypesEnteroviruses (EV) 68,69,70,71
(also novel human EVs eg. types 73-76, 79-92, 96, 97, 100, 101 [Norder etal., 2003; Oberste et al., 2004, 2005])
Most cause aseptic meningitis as well as other clinicalsyndromes; polio is the most “neurotropic”
Enteroviral meningitis by species(CIDMLS 1987-2000)
0
200
400
600
800
CVA CVB ECV EV
OverallDominant serotype2000 1999
CV A9 CV A16CV B5 CV B2ECV 7 ECV 11EV NT EV NT
Global: outbreaks CVB 5, ECV 6,9,30 endemics CVA 9, CVB 3,4 (EV71)
ECHO virus 11[30] seasonality 1991-2000
LabVISE Aust CDI 26:349; 2002
ECV30=outbreaksAseptic m’gitis
Peaks ~Asepticm’gitis
>50%
Viral meningitis - diagnosis
Clinical: fever, headache, neck stiffnessNO ∆conscious state, abnormal neuro signs
Screening WCC 25-500/µL (0-1000), lympho predominance Lab: *>50% pmn early: >90% lympho late
WCC
400 MHz 1H NMR Spectra of CSF (400 µl)Control, Viral, Fungal and Bacterial Meningitis
FlowFlow--NMR at NMR at LipoScienceLipoScience
Computer
NMR-console
U-Ultrashield magnet 400 MHz
Gilson autosampler
Clinical NMR analyser
Measuring therisk of coronaryheart diseasefrom plasma1D-NMR spectraat 48 deg C
Turnover withBEST-NMR:110 sec. with5*2 scansback mixing
< 0.5%
Pattern Recognition - PCA Scores Plot
-6.00
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-1.00
0.00
1.00
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3.00
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-10.00 0.00 10.00
PC
2
PC1
CC
C
C
C
C
CC
C
C
C
C
C
C
C
C
C
C
C C
C
CC
CC
C
C
C SASA
CG
CG
TB
NM
NM
SASP
SP
SP
EV
EV
EVEV
EV
HSV_E
HSVEV
EV
EV
HSV_E
HSV
-10 0 10PC1
6
0
-6
PC2
Viral meningitis – specific diagnosis•CSF Viral cultureHSV, VZV, *CMV, adenovirus on MRC-5 cells*Enterovirus, mumps, measles on super E-mix cells(* can expedite with culture-fluorescence at 3 days)
•NA-based methods (more sensitive, esp [+] @ 2-5 d)Single or multiplex PCR on CSF (array platforms eg MT PCR)
– enterovirus, HSV- CMV, EBV- adenovirus, other on request
-enterovirus, adenovirus typing
•Other (serum NAT kids, throat, stool samples)
Acute Viral encephalitis - Aetiology
Sporadic Epidemic*HSV 1 (2 in neonates) *Arboviruses
Australia MVEV, KUNVSE Asia/PNG: JEVAfrica/W Asia/Middle E/ WNVN America:
OtherCMV, EBV, HIV, enterovirus, adenoviruslyssavirus, Hendra virus, Nipah virus (zoonoses)
Acute disseminated (post-infectious)encephalomyelitis
CausesMeaslesRubellaMumpsInfluenzaVaricellaVacciniaNon-specific respiratory infns
FeaturesEncephalitis -fever, malaise, headache-behavioural change, confusion-convulsions-stupor/coma (late)
Exanthem/GIT illness 5-21d prior
Less common since MMR vaccine uptake improved
CSF screen Aseptic meningitis
CSF PCR HSV, VZV, arbo/enterovirusesHSV PCR Sensitivity >95% cf biopsy; lower if:
symptoms >4d, ACV >24h,high CSF RBC
CT/MRI HSVE: fronto-temporal changesMRI more sensitive MRI most useful to distinguishpost-infectious vs acute encephalitis
EEG Characteristic and focal in HSVE
Acute encephalitis - DiagnosisTest Comment
Flaviviruses – Epidemic Encephalitis
CDI (2007) 31:No. 1
Non-encephalitic disease – MVEV, KUNV, JEVacute fever, headache, myalgia, ± arthralgia ±rash
Encephalitis – MVEV, KUNV, JEVacute fever, encephalitis - ≥one of •focal neurological disease, reduced consciousness•Abnormal CT/MRI/EEG•CSF pleocytosis
Some misc. encephalitis viruses (overseas)•West Nile Virus, St Louis encephalitis (Flavivirus)•Eastern equine encephalitis, WEE, VEE (α-viruses)•La Crosse (Bunyavirus) Rabies (Lyssavirus)
Flaviviruses – Lab Confirmation•Virus isolation OR
•Positive nucleic acid test (
Asia-PacificEV 71 – outbreaks of hand foot and mouth disease F/B
-aseptic meningitis-encephalomyelitis *brainstem in Taiwan-flaccid paralysis-pulmonary oedema-mainly young children
North AmericaWest Nile virus – closely related to JEV1-2% neuroinvasive disease (88% >18yo)*aseptic meningitis*movement disorders – Parkinsonism*acute flaccid limb paralysis (10% N-I Disease)
Emerging problems
2002
WNF
WNND
Sevjar JJ, 2006
1999
8,000
N=
China
Latest
outbreak
of
EV 71
Acknowledgements
Meg Lukies, Dominic Dwyer, Alison Kesson, Bill Rawlinson, Linda Hueston