Heather Prendergast, MD, MPH, FACEP Acute Meningitis: Diagnosis, Interpretation, & Controversy

Heather Prendergast, MD, MPH, FACEP

Acute Meningitis:Acute Meningitis:Diagnosis, Interpretation, & Diagnosis, Interpretation, &

Controversy Controversy


Edward P. Sloan, MD, MPH, FACEP

2009 MEMC V Meeting2009 MEMC V Meeting

Valencia, SpainValencia, Spain16 September 200916 September 2009


Heather M. Prendergast, MD, MPH, FACEP

Associate Professor

Department of Emergency MedicineUniversity of Illinois College of Medicine

Chicago, IL


DisclosuresDisclosures• FERNE Executive BoardFERNE Executive Board• FERNE grant support by industryFERNE grant support by industry


ObjectivesObjectives• Present a relevant patient casePresent a relevant patient case• Discuss contraindications for lumbar Discuss contraindications for lumbar

puncture (LP)puncture (LP)• Review the procedure of LPReview the procedure of LP• Discuss the role of antibiotics , anti-virals, Discuss the role of antibiotics , anti-virals,

and steroids.and steroids.


A Clinical CaseA Clinical Case


ED PresentationED Presentation• 77 yo previously healthy female77 yo previously healthy female• 3 day history of fever, confusion, and 3 day history of fever, confusion, and

lethargy lethargy • Glasgow Coma Scale 13 (E4,V4,M5)Glasgow Coma Scale 13 (E4,V4,M5)• Key Aspects of Physical Exam: Key Aspects of Physical Exam:

• Unable to cooperate with neurological Unable to cooperate with neurological exam, +neck stiffness upon neck flexionexam, +neck stiffness upon neck flexion


focal exam/cranial nerve abnormalities, hx cancer, seizure, immuncompromised, altered mental status, papilledema

Indications for pre-LP head CT Indications for pre-LP head CT scanscan

Heather M. Prendergast, MD, MPH

Contraindications Contraindications

• Skin infection near site of LP

• Suspicion of increased intracranial pressure due to cerebral mass

• Uncorrected coagulopathy

• Acute spinal cord trauma

Heather Prendergast, MD, MPH FACEP

PositioningPositioning

INCORRECT CORRECT


Predicting difficult and traumatic lumbar punctures. Predicting difficult and traumatic lumbar punctures. The American Journal of Emergency MedicineThe American Journal of Emergency Medicine

2007, Volume 25, Issue 6, Pages 608-6112007, Volume 25, Issue 6, Pages 608-611K. Shah, D. McGillicuddy, J. Spear, J. EdlowK. Shah, D. McGillicuddy, J. Spear, J. Edlow

• Difficult LPDifficult LP• Requires 3 or more needle sticks or attempt by another Requires 3 or more needle sticks or attempt by another

clinicianclinician• Spine visibilitySpine visibility

• Ability to see the contour of the spinous processesAbility to see the contour of the spinous processes• Spine palpabilitySpine palpability

• Ability to palpate distinct spinous processesAbility to palpate distinct spinous processes


Comparison of Clinical GroupsComparison of Clinical Groups

DifficultDifficult Traumatic Traumatic• Spine visibleSpine visible 20.020.0 8.68.6• Spine not visibleSpine not visible 42.042.0 21.821.8• Spine palpableSpine palpable 26.726.7 12.412.4• Spine not palpable 44.2Spine not palpable 44.2 23.323.3• BMI > 30BMI > 30 42.1 42.1 18.418.4• BMI < 30BMI < 30 28.2 28.2 14.614.6• Age >65Age >65 42.9 42.9 14.314.3• Age <65Age <65 29.9 29.9 15.815.8


Ultrasound Assisted Lumbar Ultrasound Assisted Lumbar PuncturePuncture

• 46 patients46 patients• 22 Palpation Landmarks (PL)22 Palpation Landmarks (PL)• 24 Ultrasound Landmarks (UL)24 Ultrasound Landmarks (UL)

• Failure RatesFailure Rates• 6/22 PLs6/22 PLs• 1/24 ULs1/24 ULs

• Obese PatientsObese Patients• 4/7 failed PLs4/7 failed PLs• 0/5 failed ULs0/5 failed ULs

Nomura JT, et al. A randomized controlled trial of ultrasound-assisted lumbar punctureJ Ultrsound Med. 2007 ; 26(10):1341-8


Understanding Opening Understanding Opening PressuresPressures

• Normal: 60-200 mm H2O (obese patients up to 250mm H20

• Elevated: Suggest increased intracranial pressures (>250 mm H20)– Mass lesion (neoplasm, hemorrhage,

infection)– Overproduction of CSF– Defective Outflow Mechanics


CSF CompositionCSF Composition

• ColorColor• Clear and colorlessClear and colorless• TurbidTurbid

• 200 WBCs or 400 RBCs200 WBCs or 400 RBCs• Grossly BloodyGrossly Bloody

• 6000 RBCs6000 RBCs



• CellsCells• Acellular ( up to 5 WBCs and 5 Acellular ( up to 5 WBCs and 5

RBCs)RBCs)• More than 3 polymorphonuclear More than 3 polymorphonuclear

leuckocytes (PMNs) abnormalleuckocytes (PMNs) abnormal


CSF PleocytosisCSF Pleocytosis

• CSF pleocytosis – 10 white blood cells/µL,

corrected for CSF red blood cells using a ratio of 1 WBC per 500 RBCs


Calculating Predicted CSF WBC Calculating Predicted CSF WBC countcount

Predicted CSF WBC count/microL =

CSF RBC count X (peripheral blood WBC count ÷ peripheral RBC count)


Validation of Prediction Validation of Prediction Calculation in AdultsCalculation in Adults

• 720 patients

– CSF WBC count >10X predicted value

• Positive Predictive Value 48% for Bacterial Meningitis

– CSF WBC count < 10X predicted value• Negative Predictive Value 99% for

meningitis


Validation of Prediction Validation of Prediction Calculation in ChildrenCalculation in Children

• 92 children– CSF WBC count >10X predicted

value • 28/30 children (93%) bacterial

meningitis

• 57 children– CSF WBC count < 10X predicted

• 100% for predicting the absence of meningitis



• Protein– Largely excluded from CSF by blood-

CSF barrier

– Normal range (adults) 23-38 mg/dL

– False elevation• Diabetes, Presence of RBCS

– True elevation• Infectious and Noninfectious Conditions


CSF CompositionCSF Composition• GlucoseGlucose

• CSF-to-serum glucose ratioCSF-to-serum glucose ratio• Normal 0.6Normal 0.6

• Low CSF glucose concentrationsLow CSF glucose concentrations• Bacterial meningitisBacterial meningitis• Mycobacteial and Fungal CNS infectionsMycobacteial and Fungal CNS infections• M. pneumoniae and Noninfectious M. pneumoniae and Noninfectious

processesprocesses• Less than 18 mg/dL strongly predictive of Less than 18 mg/dL strongly predictive of

bacterial meningitisbacterial meningitis


CSF CompositionCSF Composition• GlucoseGlucose

• CSF-to-serum glucose ratioCSF-to-serum glucose ratio• Limited utility in Neonates, and severe Limited utility in Neonates, and severe

hyperglycemiahyperglycemia• Normal CSF glucose concentrationsNormal CSF glucose concentrations

• Viral CNS infectionsViral CNS infections• Exceptions:Exceptions:

–mumps, enteroviruses,lymphocytic mumps, enteroviruses,lymphocytic choriomeningitis(LCM), herpes simplexchoriomeningitis(LCM), herpes simplex



• LactateLactate• Elevated in bacterial meningitisElevated in bacterial meningitis• One study higher sensitivity and One study higher sensitivity and

specificity than blood glucose ratiospecificity than blood glucose ratio


CSF in CNS InfectionCSF in CNS Infection

• Bacterial MeningitisBacterial Meningitis• CSF WBC > 1000/microL ( with PMNs )CSF WBC > 1000/microL ( with PMNs )• CSF Protein >250 mg/dLCSF Protein >250 mg/dL• CSF Glucose < 45 mg/dL (2.5 mmol/L)CSF Glucose < 45 mg/dL (2.5 mmol/L)• CSF-blood glucose ratio 0.4 or less CSF-blood glucose ratio 0.4 or less

(LR 18)(LR 18)• CSF Lactate >31.53 mg/dL(3.5 mmol/L)CSF Lactate >31.53 mg/dL(3.5 mmol/L)


CSF in CNS InfectionCSF in CNS Infection

• Viral MeningitisViral Meningitis• CSF WBC < 250 /microL ( with CSF WBC < 250 /microL ( with

lymphocytes )lymphocytes )• CSF Protein <150 mg/dLCSF Protein <150 mg/dL• CSF Glucose more than 50% CSF Glucose more than 50%

of serum concentrationof serum concentration


Summary of Typical CSF FindingsSummary of Typical CSF FindingsNormalNormal BacterialBacterial Viral Viral FungalFungal

Opening Opening PressurePressure

<170 mm<170 mm >300 >300 200200 300300

CellsCells 0-50-5 >1000>1000 <1000<1000 < 500< 500PolymorphsPolymorphs 00 PredominatePredominate EarlyEarly +/- increased+/- increased

LymphocytesLymphocytes 55 LateLate PredominatePredominate IncreasedIncreased

GlucoseGlucose 60-8060-80 <40<40 >40>40 <40<40CSF plasma:CSF plasma:

Glucose ratioGlucose ratio66%66% <40%<40% NormalNormal < 30%< 30%

ProteinProtein 5-405-40 Increased Increased >200>200

+/- Increased+/- Increased

<200<200

IncreasedIncreased

>200>200

CultureCulture NegativeNegative PositivePositive NegativeNegative +positive+positive


OrganismsOrganisms

• < 3 months< 3 months ∙ ∙ E.Coli , Listeria, StreptococciE.Coli , Listeria, Streptococci

• 3 months- 18 yrs ∙ 3 months- 18 yrs ∙ N. meningitidis, H. influenzae, N. meningitidis, H. influenzae, S. pneumoniaeS. pneumoniae

• 18yrs – 50 yrs. ∙ 18yrs – 50 yrs. ∙ N. meningitidis, S. pneumoniaeN. meningitidis, S. pneumoniae

• > 50 yrs.> 50 yrs. ∙ ∙ S. pneumoniae, Listeria, S. pneumoniae, Listeria, gram-gram- negative bacillinegative bacilli


Antibiotic Choices Antibiotic Choices (Recommendations)(Recommendations)

• Good CNS penetration– Ceftriaxone– Cefotaxime– Vancomycin (controversial in children)

• Listeria (young, old, immunosuppressed)– Add high-dose ampicillin

• PCN or Cephalosporin Allergy– Meropenem or Chloramphenicol + Vancomycin


Early Vancomycin Therapy and Adverse Outcomes in Children With Pneumococcal Meningitis

PEDIATRICS Vol. 117 No. 5 May 2006, pp. 1688-1694

• Associated with a substantially increased risk of hearing loss.

• Recommend delaying the first dose of vancomycin

therapy until 2 hours after the first dose of parenteral cephalosporin


Antivirals & MeningitisAntivirals & Meningitis

• Viruses– Arbovirus

– Herpes Simplex *

– Cytomegalovirus

– Adenovirus

– HIV* Protracted course (Acyclovir 10mg/kg

IV Q8 hours)


ControversyControversySteroid Use In Bacterial Steroid Use In Bacterial

MeningitisMeningitis


Steroids & MeningitisSteroids & Meningitis


Meta-Analysis & Malawian RCTMeta-Analysis & Malawian RCT


Meta-Analysis ResultsMeta-Analysis Results

• Treatment with Dexamethasone

Benefits:– Lower mortality than Placebo (non-significant

OR= 0.58)– Lower mortality with definite meningitis

(OR=0.55)– Shorter duration of symptoms (OR=0.61)– Streptococcus Pneumoniae meningitis

(OR=0.26)


Meta-Analysis ConclusionsMeta-Analysis Conclusions

• Treatment with Dexamethasone– Did not decrease mortality in all

patients – Beneficial in the following groups

• Early presentation (< 48 hours)• Definite meningitis• Streptococcus Pneumoniae meningitis• Countries with medium or high HDI


•Dexamethasone given before or with 1st dose of antibiotics•No serious adverse effects•Consistent beneficial effect on mortality and borderline statistical beneficial effect on neurologic sequels


Corticosteroids for Acute Bacterial Meningitis Ann Emerg Med. 2009 Jul;54(1):136-7

To the Editor:We are writing in response to the systematic review abstractentitled “Corticosteroids for Acute Bacterial Meningitis”

However, we disagree with some of the conclusions: Both sets of authors, as a result of the review, advocate corticosteroids for all adults and children with suspected bacterial meningitis. While undoubtedly correct in the era before the H. influenzae vaccine, we feel this recommendation may not be the current best course of actionfor pediatric patients.


Case ResolutionCase Resolution• CT scan: No mass lesionCT scan: No mass lesion• CSF ResultsCSF Results

• WBC 5000 /WBC 5000 /μμLL• RBC 5 /microLRBC 5 /microL• CSF blood glucose ratio 0.2CSF blood glucose ratio 0.2

• Gram stain: gram positive rodsGram stain: gram positive rods

Diagnosis: Meningitis due to ListeriaDiagnosis: Meningitis due to Listeria


RecommendationsRecommendations

• Calculate CSF-blood glucose ratio. •0.4 or less (LR 18) bacterial meningitis

• Determine the predicted CSF WBC count•Negative Predictive Value 99% for bacterial meningitis


RecommendationsRecommendations

• Do not delay administering antibiotics as delays have been associated with worsening clinical outcomes

• Empiric antibiotic choice is based upon broad spectrum coverage of common pathogens

• Use of dexamethasone has shown benefit in selected cases of adult bacterial meningitis less so in children


ConclusionsConclusions• Primary indications for LP is to assess for

meningitis or subarachnoid hemorrhage• Most patients do not require CT scan to

rule out mass lesions prior to LP• Clinical examination can guide decision for

neuroimaging• Elevated opening pressures indicate

increase intracranial pressures


Questions?Questions?

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Heather Prendergast, MD, MPH, FACEP Acute Meningitis: Diagnosis, Interpretation, & Controversy