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CNS InfectionsCNS Infections
11-23-0411-23-04
Chapter 235Chapter 235
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Bacterial Bacterial MeningitisMeningitis
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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
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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
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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
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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
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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
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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
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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 (-) __ __ ++ ++
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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
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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
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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
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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
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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
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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
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Emperic AntiviralsEmperic Antivirals
Concern of herpesConcern of herpes Acyclovir 10mg/kg IV Q 8 hoursAcyclovir 10mg/kg IV Q 8 hours
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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.
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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
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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
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Viral MeningitisViral Meningitis
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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 (-)
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Viral EncephalitisViral Encephalitis
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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
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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)
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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
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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
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Clinical featuresClinical features
New psych symptomsNew psych symptoms Cognitive deficit (aphasia, amnesia, Cognitive deficit (aphasia, amnesia,
confusion)confusion) SeizureSeizure Movement d/oMovement d/o
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DiagnosisDiagnosis
MRI-more sensitive than CTMRI-more sensitive than CT CTCT EEGEEG LP-findings consistent with aseptic LP-findings consistent with aseptic
meningitismeningitis
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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
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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
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Brain AbscessBrain Abscess
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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
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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
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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
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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
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DiagnosisDiagnosis
CT with contrastCT with contrast LP contraindicatedLP contraindicated Biopsy or aspiration for confirmationBiopsy or aspiration for confirmation
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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
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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
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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