Infectious Disease Dept., Digestive Diseases Research .Infectious Disease Dept., Digestive Diseases

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H i J bb i MD MPH ID & TMHossainJabbari;MD,MPH,ID&TMInfectiousDiseaseDept.,

Digestive Diseases Research CenterDigestiveDiseasesResearchCenter

CNS i f iCNS infections

M i itiMeningitisE h li iEncephalitis

DefinitionsMeningitis: inflammationofthemembranescoveringthebrainorspinalcord(piaand

h id )arachnoidmater)Encephalitis:i fl ti f thinflammationofthecerebralcortex(tissue)Meningoencephalitis:Meningoencephalitis:inflammationofthemeninges, subarachnoidmeninges,subarachnoidspaceandcortex

Seminars in Neurology: 2000: 20(3)



M i h li iMeningoencephalitis

M i i i l ifi iMeningitis classification

Acute meningitis gSub acute meningitisgChronic meningitis

M i i i l ifi iMeningitis classification

Bacterial (Pyogenic) ( y g )Granulomatous Lymphocytic

Epidemiologyp gyIncidence

2.5to3.5casesper100,000peoplep , p p0.16to0.45per1,000livebirths

CommonOrganisms:g1986 :H.influenzae(45%),S.pneumoniae(18%),N.meningitidis(14%)1995 :S.pneumoniae(47%),N.meningitidis(25%),


Seminars in Neurology: 2000 20(3)

Meningitis etiologiesPneumococcal meningitisHaemophilus influenzae meningitisSt h l l i itiStaphylococcal meningitisMeningococcal meningitisMeningococcal meningitisTuberculous meningitis

Meningitis etiologiesFungal gParasitic causes (cryptococcal meningitis, Hi t l meningitis andHistoplasma meningitis, and amebic meningoencephalitis)amebic meningoencephalitis)

Meningitis etiologiesViral meningitisg Enterovirus : 85% of all viral

causes including:oEchovirusesoEchovirusesoCoxsackieviruses A and BoPoliovirusesoThe numbered enterovirusesoThe numbered enteroviruses

Meningitis etiologiesViral meningitisg Herpes family (HSV1,

HSV2, EBV, CMV, Mumps Mumps Polio virusPolio virus

Meningitis etiologiesViral meningitisg Lymphocytic choriomeningitis

viruses (LCMV) Adenoviruses Adenoviruses MeaslesMeasles HIV

Meningitis etiologiesViral meningitisg Arborviruses including:(Togavirus family; St. Louis encephalitis West

Nile Japanese B and Murray Valley virusesNile, Japanese B, and Murray Valley viruses, from the Flavivirus family; and California group and Jamestown Canyon viruses from theand Jamestown Canyon viruses, from the Bunyaviridae family. Colorado tick fever is caused by a coltivirus)caused by a coltivirus)

Viral Meningitis

Finland study:Finland study: Aseptic meningitis: etiology found in 66% patientspViral encephalitis: etiology only found in 3636%% casesViral prodrome, sore throat, myalgias, ill contacts, GI complaints; summer/fall season

i (2 %)Most common= enteroviruses (25%)EchovirusesC ki iCoxsackievirus

Viral MeningitisViral MeningitisClassified in aseptic meningitisp gMay be difficult to initially separate from partially treated bacterialfrom partially treated bacterial meningitis (obligates empiric treatment for bacterial)for bacterial)Differentiate from true aseptic (drug related such as NSAIDsrelated such as NSAIDs, paraneoplastic)

Meningitis etiologiesNon- infectious causes of meningitis: Drugs, Autoimmune di d i i GBSdisorders, migraine, GBSx,.

Meningitis etiologiesAnd the last but not the least!

TB MeningitisTB Meningitis

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Pathophysiology: common routes

H dHematogenousspreadcommonNasopharynxNasopharynxTraumaInstrumentationInfection foci in neighboring organsInfectionfociinneighboringorgans

Meningitis risk factors/Age>60y/o

Age5y/oDM,renaloradrenalinsufficiency,Hypoparathyroidism,CFyp p y ,HIVdorm residents)dormresidents)dormresidents)l dSplenectomyandSCA


Meningitis risk factorsAlcoholismandcirrhosisSinusitis, COM, MastoiditisSinusitis,COM,MastoiditisDuraldefect(eg,traumatic,surgical,congenital)congenital)MajorthalassemiaIDUEndocarditisSomecranialcongenitaldeformities

PathophysiologyPathophysiologyCell wall and membrane products of organism disrupt capillary endothelium of CNS (BBB)disrupt capillary endothelium of CNS (BBB)Margination and transmigration of PMNs across endothelia in CSFo Release of cytokines and chemokines into the

CNSInflammation of subarachnoid spaceNeurologic Sequelae: 10 % of surviving patients

i l h i l i dSensorineural hearing loss, seizures, and hydrocephalus

Clinical ManifestationsClinical ManifestationsFeverFeverHeadacheNeckpain or stiffnessNeckpain or stiffnessInfants:o May exhibit irritability, vomiting, poor feedingy y, g, p go Nuchal rigidity or bulging fontanelle present in

roughly 50% of infants and young childrenOther: o N&V, photophobia, irritability, altered mental

t t diff h t histatus, diffuse rash, petechia, purpura

Physical FindingsPhysical Findings

Kernigssign Brudzinskissign

Ski hSkin rashes Skin rash pathogenesis:a. Septicemiab Wide spread endothelial damageb. Wide spread endothelial damage c. Activation of coagulationd. Thrombosis and platelets aggregatione. Reduction of platelets (cosumption )f. Bleeding: rashes

2.adrenal hemorrhage2.adrenal hemorrhage Arenal hemorrhage is called Waterhouse-Friderichsen Syndrome.It cause acute adrenal insufficiency and is uaually fataly

S ifi iSpecific presentationsHemorrhagic CSF:

TraumaTraumaBleeding diathesisSAHSAHAnthraxHSV encephalitisHSV encephalitisListeria Monocytogen

C li iComplicationsAntibiotic treatment full recoveryDelayed or untreated cases can be fatalDelayed or untreated cases can be fatal (25%)Healing by fibrosis cause obliteration of subarachenoid space HYDROCEPHALUS pBrain abscessSeptic shock and skin rashes, why ?

C li iComplications

VentriculitisEmpyemaCerebritisAbscess formation

Long-term Neurological Complications

Adverse Outcomes at One Year of Age of 12 Infants With Bacterial Meningitisg

Category of Disability Number

Development delay 10

Cerebral palsy 1

Microcephaly 3

Hemiparesis 3

Hearing loss 1

Blindness 2Blindness 2

Seizure disorder 3

Total number of disabilities exceeds the number of infants owing to the presence of multipleTotal number of disabilities exceeds the number of infants owing to the presence of multiple disabilities in most subjects

Klinger G, et al. Pediatrics. 2000;106:477-482

DiagnosisLumbar puncture

Cell count with differentialProteinProteinGlucoseGram stain of CSF

Cultures of CSF blood and urineCultures of CSF, blood and urineADA

So what is a sensible rule for LP?So what is a sensible rule for LP?At a minimum, if you want to avoid missing y gmeningitis (and deaths and handicap from it), and avoid wasting antibiotics, at least LP ) gthose with history of fever and one of:

Bulging fontanelleg gStiff neckFits if age 6 yrsFits if age 6 months or 6 yrsPartial or focal fitsReduced consciousnessReduced consciousness

CSF pressurepNormal opening pressure :p g p

10 to 100 mm H2O (in < 8 y/o )60 200 H2O ( 8 / )60 to 200 mm H2O (> 8 y/o) up to 250 mm H2O (in obese patients)p ( p )

CSF Findings in Infants and ChildrenComponent Normal





CSF Findings in Infants and Children


0-6 0-30 >1000 100-500


0 2-3 >50 < 40(%)Glucose (mg/dL)

40-802/3 serum

32-121 100 50-100


0-2 0-2 0-10 0-2

CSF Findings in meningitis

Value of LP findings Acute bacterial meningitis

All the true acute bacterial meningitis cases

B d id t l i h l f lBedside assessment alone is very helpful

75% of acute bacterial meningitis cases can be detected by examining for CSF cloudiness orfor CSF cloudiness or turbidity at the bedside.

CSF Cloudiness / TurbidityCSF Cloudiness / Turbidity

A simple test of CSF turbidity is to see if normal print can benormal print can be read easily through the sample CSF sho ld be cr stalshould be crystal clear.

Cloudiness usuallyCloudiness usually appears at CSF WBC counts > 200 106 WBC L200x106 WBC per L

CSF culture is great but if it is not il bl i ill idavailable a microscope will provide nearly all you need to know

82% of acute bacterial meningitis cases can be detected by either turbidity y yor a CSF white cell count and using a cut-off of >50 WBC per L (>50 x 106WBC per L. (>50 x 106WBC per L)

CSF microscopy, blood and CSF glucose measures are highly sensitive

96% of acute bacterial meningitis cases can bemeningitis cases can be detected by turbidity, a CSF white cell count of >50 Wbc per L (>50 x 106 Wbc per L) or a CSF glucose to Blood glucose ratio

CSF discoloration

Empiric TreatmentEmpiric Treatment

T LP i i i i i fTry to get LP prior to initiation of antibiotics but begin intravenous gempiric therapy if LP cannot be performed within 30 minutesperformed within 30 minutes from presentation !!

Treatment ConsiderationsTreatment Considerations

AllergiesEmpiric Therapy: Age specificp py g pCSF PenetrationCultures/SensitivitiesCultures/SensitivitiesPathogen Specific TherapyDuration of Therapy


Age Major