CNS InfectionsCNS Infections

11-23-0411-23-04

Chapter 235Chapter 235

Bacterial Bacterial MeningitisMeningitis

EpidemiologyEpidemiology

400 per 100,000 in neonates400 per 100,000 in neonates 1-2 per 100,000 in adults1-2 per 100,000 in adults S pneumoniae & N meningitidis m/cS pneumoniae & N meningitidis m/c

HIB vaccine has been very effectiveHIB vaccine has been very effective Mortality Mortality

5% in children beyond infancy5% in children beyond infancy 25% in neonates and in adults25% in neonates and in adults

PathophysiologyPathophysiology

S. pneumonia and N. meningitidis (and S. pneumonia and N. meningitidis (and H. influenzae) are encapsulated which H. influenzae) are encapsulated which provides them with increased ability to provides them with increased ability to invade BBBinvade BBB

Upper airwayUpper airway bloodstream bloodstream subarachnoid spacesubarachnoid space subcapsular subcapsular constituents trigger inflammationconstituents trigger inflammation fever, meningimus, change in MSfever, meningimus, change in MS brain/meningeal edemabrain/meningeal edema decreased decreased CSF drainageCSF drainage hydrocephalus hydrocephalus increased ICPincreased ICP ICP>CPP ICP>CPP

Clinical FeaturesClinical Features

25% of adult cases “classic”25% of adult cases “classic” Rapid development ofRapid development of

FeverFever HAHA Stiff neckStiff neck PhotophobiaPhotophobia Change in MSChange in MS

Nonspecific signs/symptoms in very Nonspecific signs/symptoms in very young/oldyoung/old

25% will develop seizures25% will develop seizures

Clinical FeaturesClinical Features

HistoryHistory Living conditionsLiving conditions

College dorm/barracksCollege dorm/barracksN meningitidisN meningitidis TraumaTrauma

Recent neurosurgeryRecent neurosurgeryStaph/gram(-) rodStaph/gram(-) rod ImmunocompetenceImmunocompetence Immunization hxImmunization hx

NoneNoneHiBHiB Antibiotic useAntibiotic use

Clinical FeraturesClinical Feratures

Physical ExamPhysical Exam BrudzinskiBrudzinski

Passive neck flexPassive neck flex hips & knees flex hips & knees flex KernigKernig

Flex hip, ext kneeFlex hip, ext knee hamstrings contract hamstrings contract SkinSkin

PurpuraPurpura Petechiae/splinter hem, pustular Petechiae/splinter hem, pustular

lesionslesionsmicroembolimicroemboli FundiFundi Neuro ExamNeuro Exam

DiagnosisDiagnosis

ParenchymalParenchymal CT is the imaging of choiceCT is the imaging of choice

Brain abscess, encephalitis, toxoplasmosisBrain abscess, encephalitis, toxoplasmosis

MeningealMeningeal Lumbar punctureLumbar puncture

Neoplasm, CNS vasculitis, SAHNeoplasm, CNS vasculitis, SAH

DiagnosisDiagnosisParameter Parameter (normal)(normal)

BacterialBacterial ViralViral NeoplasticNeoplastic FungalFungal

OP (<170 mm OP (<170 mm CSF)CSF)

>300mm>300mm 200mm200mm 200200 300mm300mm

WBC WBC (<5mononuclea(<5mononuclear)r)

>1000>1000 <1000<1000 <500<500 <500<500

%PMN’s (0)%PMN’s (0) >80%>80% 1-50%1-50% 1-50%1-50% 1-50%1-50%

Glucose Glucose (>40mg/dL)(>40mg/dL)

<40<40 >40>40 <40<40 <40<40

Protein Protein (<50mg/dL)(<50mg/dL)

>200>200 <200<200 >200>200 >200>200

Gram stain (-)Gram stain (-) ++ __ -- __

Cytology (-)Cytology (-) __ __ ++ ++

DiagnosisDiagnosis

An aseptic profileAn aseptic profile Must think about…Must think about…

Partially treated bacterial infectionPartially treated bacterial infection Bacterial infections adjacent to the Bacterial infections adjacent to the

subarachnoid spacesubarachnoid space

DiagnosisDiagnosis Tests to order on the CSFTests to order on the CSF

Tube #1 cell count with diffTube #1 cell count with diff Tube #2 protein,glucoseTube #2 protein,glucose Tube #4 cell count with diff, gram stain/cultureTube #4 cell count with diff, gram stain/culture Tube #3Tube #3

Viral culturesViral cultures Borrelia (lyme disease)Borrelia (lyme disease) India ink/cryptococcal antigen (immunocomp)India ink/cryptococcal antigen (immunocomp) Acid fast stain/culture for mycobacteria (TB)Acid fast stain/culture for mycobacteria (TB) Latex agglutination for bacterial AntigensLatex agglutination for bacterial Antigens PCRPCR

Herpes, arbovirusHerpes, arbovirus

Lumbar PunctureLumbar Puncture

ContraindicationsContraindications Infection in overlying skinInfection in overlying skin RelativeRelative

CoagulopathyCoagulopathy ThrombocytopeniaThrombocytopenia

If delay is anticipated obtain blood If delay is anticipated obtain blood cultures and GIVE antibioticscultures and GIVE antibiotics You have 2 hours after ATB given before You have 2 hours after ATB given before

sensitivity is effectedsensitivity is effected

Lumbar PunctureLumbar Puncture

Considerations for not obtaining CT Considerations for not obtaining CT before performing LPbefore performing LP Age <60Age <60 ImmunocompetentImmunocompetent No h/o CNS diseaseNo h/o CNS disease No recent seizure (<1week)No recent seizure (<1week) Normal sensorium & cognititionNormal sensorium & cognitition No papilledemaNo papilledema No focal neuro deficitsNo focal neuro deficits

TreatmentTreatment

First priorityFirst priority AntibioticsAntibiotics

Second priority in some casesSecond priority in some cases Anti-inflammatoriesAnti-inflammatories

Third priorityThird priority Counter the adverse effects of Counter the adverse effects of

increased ICP & vasculopathyincreased ICP & vasculopathy

Emperic AntibioticsEmperic AntibioticsAge/SpecialAge/Special Gram StainGram Stain DrugDrug18-50y/o18-50y/o NegativeNegative Ceftriaxone 2g IV Ceftriaxone 2g IV

++

vanco 1g IV or rifampinvanco 1g IV or rifampin

>50 y/o>50 y/o NegativeNegative Ceftriaxone Ceftriaxone

+ +

ampicillin ampicillin

+ +

vanco or rifampinvanco or rifampin

Recent penetrating Recent penetrating head injury/ head injury/ surgery/shuntsurgery/shunt

NegativeNegative Vanco 25mg/kg then 19mg/kg Vanco 25mg/kg then 19mg/kg using Matzke nonogram using Matzke nonogram

++

ceftazidimeceftazidime

immunocompromiseimmunocompromisedd

Negative----------------------------------Negative----------------------------------------GPC----------------------------------------GPC--------------------------------------------GNC----------------------------------------GNC------------------------------------------GPR----------------------------------------GPR--------------------------------------------GNR----------------------------------------GNR------------------------------------------

Vanco+ amp+ ceftazidimeVanco+ amp+ ceftazidime

Ceftriaxone + vancoCeftriaxone + vanco

Pen GPen G

Amp + gentAmp + gent

Cetazidime + aminoglycosideCetazidime + aminoglycoside

Emperic AntiviralsEmperic Antivirals

Concern of herpesConcern of herpes Acyclovir 10mg/kg IV Q 8 hoursAcyclovir 10mg/kg IV Q 8 hours

SteroidsSteroids

DexamethasoneDexamethasone 10mg IV 15 minutes prior to antibiotics10mg IV 15 minutes prior to antibiotics Shown to decrease M&M in S. Shown to decrease M&M in S.

pneumoniae but NOT N. meningitidispneumoniae but NOT N. meningitidis N Engl J Med 2002; 347:1549-1556, Nov 14, N Engl J Med 2002; 347:1549-1556, Nov 14,

2002. 2002.

ComplicationsComplications

SeizuresSeizures HyponatremiaHyponatremia SIADHSIADH CVACVA CoagulopathiesCoagulopathies Cognitive deficits, epilepsy, Cognitive deficits, epilepsy,

hydrocephalus, hearing loss affect hydrocephalus, hearing loss affect 25% of survivors25% of survivors

ChemoprophylaxisChemoprophylaxis

Household/school/daycare contacts Household/school/daycare contacts last 7 dayslast 7 days

Direct exposure to secretionsDirect exposure to secretions Kissing, sharing utensils/toothbrushes, Kissing, sharing utensils/toothbrushes,

mouth to mouth, intubation without a mouth to mouth, intubation without a maskmask

First line: rifampin 10mg/kg (max First line: rifampin 10mg/kg (max dose 600mg) Q12h x 4 dosesdose 600mg) Q12h x 4 doses

Alternative: ceftriaxone, cipro, Alternative: ceftriaxone, cipro, sulfisoxazolesulfisoxazole

Viral MeningitisViral Meningitis

Viral MenigitisViral Menigitis

85% secondary to85% secondary to Echo-Echo- CoxsackieCoxsackie Entero-Entero-

Also consider HSV, and EBVAlso consider HSV, and EBV Neutrophils may predominate in the Neutrophils may predominate in the

CSF in the first 24 hoursCSF in the first 24 hours Consider starting ATB’s until Consider starting ATB’s until

cultures come back (-)cultures come back (-)

Viral EncephalitisViral Encephalitis

Viral EncephalitisViral Encephalitis

Infection of brain parenchymaInfection of brain parenchyma Presents of neurological Presents of neurological

abnormalities distinguish it from abnormalities distinguish it from meningitismeningitis

EpidemiologyEpidemiology

Incidence is 1/10 of bacterial meningitisIncidence is 1/10 of bacterial meningitis HSV-1, zoster, EBV,CMV, rabies, arboHSV-1, zoster, EBV,CMV, rabies, arbo

ArboArbo LAC (La Crosse)-diagnosed most frequentlyLAC (La Crosse)-diagnosed most frequently SEE(St Louis)-20% mortality in elderlySEE(St Louis)-20% mortality in elderly WEE(Western)- causes seizures in 90% of infected WEE(Western)- causes seizures in 90% of infected

infants, permanent neuro deficits in 50%infants, permanent neuro deficits in 50% EEE(Eastern)- most devastating, mortality 70%EEE(Eastern)- most devastating, mortality 70% WNV(West Nile)WNV(West Nile)

PathophysiologyPathophysiology

Portals of entryPortals of entry Arbo-transmitted by mosquitoes, ticksArbo-transmitted by mosquitoes, ticks Rabies-bite by infected animalRabies-bite by infected animal

Hematogenous dissemination v. Hematogenous dissemination v. travel backwards on axons travel backwards on axons (HSV,HZV,rabies)(HSV,HZV,rabies)

Dysfunction & damage caused by Dysfunction & damage caused by disruption of neural cell function & disruption of neural cell function & inflammationinflammation

Pathophysiology cont.Pathophysiology cont.

Gray matter predominately affectedGray matter predominately affected Cognitive/psychiatric signs, lethargy, Cognitive/psychiatric signs, lethargy,

seizuresseizures White matter affected in post-White matter affected in post-

infectious encephalomyelitisinfectious encephalomyelitis

Clinical featuresClinical features

New psych symptomsNew psych symptoms Cognitive deficit (aphasia, amnesia, Cognitive deficit (aphasia, amnesia,

confusion)confusion) SeizureSeizure Movement d/oMovement d/o

DiagnosisDiagnosis

MRI-more sensitive than CTMRI-more sensitive than CT CTCT EEGEEG LP-findings consistent with aseptic LP-findings consistent with aseptic

meningitismeningitis

DifferentialDifferential

Exclude the killersExclude the killers Bacterial meningitis & SAHBacterial meningitis & SAH

More meningeal symptomsMore meningeal symptoms Lyme, TB, fungal, bacterial, viral, Lyme, TB, fungal, bacterial, viral,

neoplasticneoplastic More parenchymal symptomsMore parenchymal symptoms

Abscess, bacterial endocarditis, post-Abscess, bacterial endocarditis, post-infectious encephalomyelitis, toxic or infectious encephalomyelitis, toxic or metabolic encephalopathymetabolic encephalopathy

TreatmentTreatment

HSV: acyclovir 10mg/kg IVHSV: acyclovir 10mg/kg IV CMV: ganciclovirCMV: ganciclovir Rabies/EEE/HSVRabies/EEE/HSVdevastating & devastating &

usually fatal or residual deficitsusually fatal or residual deficits

Brain AbscessBrain Abscess

Brain AbscessBrain Abscess

Focal pyogenic infectionFocal pyogenic infection Pus-filled cavity ringed by Pus-filled cavity ringed by

granulation tissue & outer fibrous granulation tissue & outer fibrous capsule surrounded by edematous capsule surrounded by edematous brain tissuebrain tissue

EpidemiologyEpidemiology

Paranasal sinus focusParanasal sinus focus 10-30 y/o10-30 y/o

OticOtic Bimodal: <20 y/o & >40 y/oBimodal: <20 y/o & >40 y/o

PathophysiologyPathophysiology

Hematogenous spreadHematogenous spread 1/3 of cases1/3 of cases

Contiguous (middle ear, sinus, teeth)Contiguous (middle ear, sinus, teeth) 1/3 of cases1/3 of cases Otogenic (Bacteroides)Otogenic (Bacteroides)temporal temporal

lobe/cerebellumlobe/cerebellum Sinogenic & odontogenic(anaerobic & Sinogenic & odontogenic(anaerobic &

microaerophilic streptococci)microaerophilic streptococci)frontal frontal lobelobe

Clinical FeaturesClinical Features

Classic triadClassic triad HA, fever, focal deficitHA, fever, focal deficit

<1/3 of cases<1/3 of cases Toxic appearance is rareToxic appearance is rare Seizures, vomiting, confusion, obtundation Seizures, vomiting, confusion, obtundation

possiblepossible Frontal lobe-hemiparesisFrontal lobe-hemiparesis Temporal lobe- homonymous superior Temporal lobe- homonymous superior

quadrant visual field deficit or aphasiaquadrant visual field deficit or aphasia Cerebellum-limb incoordination or Cerebellum-limb incoordination or

nystagmusnystagmus

DiagnosisDiagnosis

CT with contrastCT with contrast LP contraindicatedLP contraindicated Biopsy or aspiration for confirmationBiopsy or aspiration for confirmation

TreatmentTreatmentPresumed Presumed SourceSource

Primary Primary Empiric TxEmpiric Tx

Alternative TxAlternative Tx

OtogenicOtogenic Cefotaxime 2g IV q8hCefotaxime 2g IV q8h Bactrim 5mg/kg IV q6hBactrim 5mg/kg IV q6h

++

Flagyl 1giv then 500mg Flagyl 1giv then 500mg q6 or chloramphenicolq6 or chloramphenicol

Sinogenic or Sinogenic or odontogenicodontogenic

Pen 24 million units/d IV Pen 24 million units/d IV divided q4hdivided q4h

+ +

Flagyl 1g IV then 500mg Flagyl 1g IV then 500mg q6hq6h

Pen (same dose)Pen (same dose)

++

Chloramphenicol Chloramphenicol 100mg/kg/d divided q6h100mg/kg/d divided q6h

Penetrating Penetrating trauma or trauma or neurosurgeryneurosurgery

Nafcillin 2g IV q4hNafcillin 2g IV q4h

++

Ceftazidime 2g IV q8hCeftazidime 2g IV q8h

Vanco 15mg/kg (max Vanco 15mg/kg (max 1g)IV q6h1g)IV q6h

++

Ceftazidime 2g IV Ceftazidime 2g IV

HematogenousHematogenous Pen 24 million units/d Pen 24 million units/d divided q4hdivided q4h

++

Flagyl 1g then 500mg Flagyl 1g then 500mg q6hq6h

Pen (same dose)Pen (same dose)

++

Chloramphenicol Chloramphenicol 100mg/kg/d divided q6h100mg/kg/d divided q6h

No obvious No obvious sourcesource

Cefotaxime 2g IV q6hCefotaxime 2g IV q6h

++

Flagyl 1g IV then 500mg Flagyl 1g IV then 500mg q6hq6h

No recommendationsNo recommendations

QuestionsQuestions 1. CSF analysis returns with the following 1. CSF analysis returns with the following

values: glucose 20 WBC 1200 Protein values: glucose 20 WBC 1200 Protein 300. This profile is consistent with300. This profile is consistent with A. Bacterial meningitisA. Bacterial meningitis B. viral meningitisB. viral meningitis C. Fungal meningitisC. Fungal meningitis

2. Which of the following is an absolute 2. Which of the following is an absolute contraindication to performing an LPcontraindication to performing an LP A. CoagulopathyA. Coagulopathy B. Infection of the overlying skinB. Infection of the overlying skin C. thrombocytopeniaC. thrombocytopenia

QuestionsQuestions 3. T/F Steroids have been shown to 3. T/F Steroids have been shown to

decrease morbidity & mortality in decrease morbidity & mortality in meningitis caused by Strep pneumomeningitis caused by Strep pneumo

4. T/F Brain abscesses are confirmed by 4. T/F Brain abscesses are confirmed by LP.LP.

5. Which antibiotic regimen should be 5. Which antibiotic regimen should be initiated in an immunocompromised patient initiated in an immunocompromised patient suspected of having bacterial meningitis suspected of having bacterial meningitis without any allergieswithout any allergies A. Pen GA. Pen G B. Ceftriaxone & vancoB. Ceftriaxone & vanco C. Vanco, gent, & ceftazidimeC. Vanco, gent, & ceftazidime

Answers: 1. A 2. B 3. T 4. F 5. CAnswers: 1. A 2. B 3. T 4. F 5. C