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

-5.00

-4.00

-3.00

-2.00

-1.00

0.00

1.00

2.00

3.00

4.00

5.00

6.00

-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