Meningitis “An Update” Saad A. Alsaleh. Objectives Introduction Introduction Classification...

MeningitisMeningitis“An Update”“An Update”

Saad A. AlsalehSaad A. Alsaleh

ObjectivesObjectives

IntroductionIntroduction ClassificationClassification Can you exclude meningitis without an Can you exclude meningitis without an

LP?LP? When is a CT necessary?When is a CT necessary? Bacterial meningitis scores?Bacterial meningitis scores? What antibiotics should I use?What antibiotics should I use? What about steroids?What about steroids? ComplicationsComplications SummarySummary

IntroductionIntroduction

Meningitis is the inflammation of Meningitis is the inflammation of the meninges.the meninges.

Caused by bacteria, viruses or Caused by bacteria, viruses or rarely other causes.rarely other causes.

The The WHOWHO estimates that estimates that bacterial meningitis strikes bacterial meningitis strikes 426,000 children younger than 5 426,000 children younger than 5 years annually, with 85,000 years annually, with 85,000 deaths. deaths.


In History:In History:• Meningitis was first accurately Meningitis was first accurately

identified by the Swiss Vieusseux (a identified by the Swiss Vieusseux (a scientific -literary association) during scientific -literary association) during an outbreak in Geneva, Switzerland an outbreak in Geneva, Switzerland in 1805.in 1805.

• In the 1In the 1stst decade of the 20th decade of the 20th century, meningococcal meningitis century, meningococcal meningitis was associated with a mortality rate was associated with a mortality rate of 75 to 80 %. of 75 to 80 %.


In History:In History:• In the 1920s, at Boston Children's In the 1920s, at Boston Children's

Hospital 77 of 78 children who had Hospital 77 of 78 children who had Haemophilus influenzae M. died and all Haemophilus influenzae M. died and all patients (300) with pneumococcal M. patients (300) with pneumococcal M. died.died.

• In the past 15 years, mortality rates In the past 15 years, mortality rates for:for:

• meningococcal meningitis 10 % meningococcal meningitis 10 % • H. influenzae meningitis 5 % H. influenzae meningitis 5 % • Pneumococcal meningitis 20 %Pneumococcal meningitis 20 %

ClassificationClassification

InfectiousInfectious• BacterialBacterial• ViralViral• FungalFungal

Non-infectiousNon-infectious• Drug-InducedDrug-Induced• AutoimmuneAutoimmune• NeoplasticNeoplastic

22%

54%

24%

Bacterial Viral Non-Infectious

Bacterial meningitis in Canada (1994-2001). Deeks SL. Canadian Communicable Disease Report. Dec

2005.

Bacterial meningitis in Saudi Arabia: Bacterial meningitis in Saudi Arabia: the impact of Haemophilus the impact of Haemophilus

influenzae type b vaccination.influenzae type b vaccination.Almuneef M, Alshaalan M, Memish Z, Alalola S.Almuneef M, Alshaalan M, Memish Z, Alalola S.

J Chemother. 2001 Apr;13 Suppl 1:34-9 J Chemother. 2001 Apr;13 Suppl 1:34-9

57%31%

7%5%

Haemophilusinfluenzae type bStreptococcuspneumoniae group BstreptococcusOther

Viral MeningitisViral Meningitis

85%

5%

4% 6%

Enterovirus

Arbovirus

Herpes FamilyViruses

Other

Clinical Clinical FeaturesFeatures

(Can you exclude meningitis (Can you exclude meningitis without an LP? )without an LP? )

Clinical Features:Clinical Features:SymptomsSymptoms

Clinical Features:Clinical Features:SignsSigns

Signs of shock: Signs of shock: ↓ ↓ BP, tachycardia, poor BP, tachycardia, poor capillary refill, oliguria.capillary refill, oliguria.

Altered mental status, from irritability to Altered mental status, from irritability to somnolence, delirium, and coma.somnolence, delirium, and coma.

Meningeal signs:Meningeal signs: • Photophobia.Photophobia.• neck stiffness. neck stiffness. • positive Kernig’s or Brudzinski’s signs positive Kernig’s or Brudzinski’s signs

(sensitivity & specificity are (sensitivity & specificity are uncertain).uncertain).


Signs of Signs of ↑↑ ICP: papilloedema, ICP: papilloedema, anisocoria, ptosis, 6anisocoria, ptosis, 6thth nerve palsy, nerve palsy, bradycardia with HTN.bradycardia with HTN.

Focal neurological signs in up to Focal neurological signs in up to 15% of patients and are 15% of patients and are associated with a worse associated with a worse prognosis.prognosis.

Generalized or focal seizures are Generalized or focal seizures are observed in as many as 33% of observed in as many as 33% of patients.patients.


Skin findings: petechial or purpuric Skin findings: petechial or purpuric rash (meningococcal meningitis).rash (meningococcal meningitis).

Signs of DIC.Signs of DIC. Extracranial infection (eg, sinusitis, Extracranial infection (eg, sinusitis,

otitis media, mastoiditis, otitis media, mastoiditis, pneumonia, infective endocarditis) pneumonia, infective endocarditis) may be noted.may be noted.

Meningococcal Meningococcal MeningitisMeningitis


In 1909 In 1909 Brudzinski reported that, for patients with bacterial or tuberculous meningitis:•Kernig’s sign was 57% sensitive.•Brudzinski’s sign was 96%

sensitive.Verghese A, Gallenmore G. Kernig’s and Brudzinski’s signs

revisited.

Rev Infect Dis 1987; 9:1187–92.

““The diagnostic accuracy of Kernig's The diagnostic accuracy of Kernig's sign, Brudzinski's sign, and nuchal sign, Brudzinski's sign, and nuchal rigidity in ADULTS with suspected rigidity in ADULTS with suspected

meningitis”meningitis” Clin Infect Dis 35 (1): 46-52Clin Infect Dis 35 (1): 46-52

Thomas K, Hasbun R, Jekel J, Quagliarello V (2002). Thomas K, Hasbun R, Jekel J, Quagliarello V (2002).

the sensitivity of both Kernig’s sign and Brudzinski’s sign is 5%

the specificity of both signs is 95%

Nuchal rigidity had a sensitivity of 30% & specificity of 68%

The Rational Clinical ExaminationThe Rational Clinical Examination

Does this adult patient have Does this adult patient have acute meninigitis?acute meninigitis?

Attia J. JAMA. 281:2. 175 (1999).Attia J. JAMA. 281:2. 175 (1999).

The Rational Clinical ExaminationThe Rational Clinical Examination

Does this adult patient have Does this adult patient have acute meninigitis?acute meninigitis?

Attia J. JAMA. 281:2. 175 (1999).Attia J. JAMA. 281:2. 175 (1999).

Clinical history has low accuracy in the Clinical history has low accuracy in the Dx of Meningitis.Dx of Meningitis.

The absence of fever, neck stiffness AND The absence of fever, neck stiffness AND altered mental status effectively altered mental status effectively eliminates meningitis from the eliminates meningitis from the differential diagnosis (Sensitivity of at differential diagnosis (Sensitivity of at least 1 finding is 99-100%)least 1 finding is 99-100%)

The presence of jolt accentuation in a The presence of jolt accentuation in a patient with fever and headache is 100% patient with fever and headache is 100% sensitive and 54% specific for meningitis.sensitive and 54% specific for meningitis.

InvestigationInvestigationss

InvestigationsInvestigations

Complete blood count (CBC) with Complete blood count (CBC) with differentialdifferential

Coagulation profile (DIC)Coagulation profile (DIC) Serum glucose (to compare)Serum glucose (to compare) Erythrocyte sedimentation rate (ESR)Erythrocyte sedimentation rate (ESR) U/E (SIADH) and LFTU/E (SIADH) and LFT Cultures of blood, nasopharynx, respiratory Cultures of blood, nasopharynx, respiratory

secretions, urine, and skin lesions. secretions, urine, and skin lesions. Bacterial antigen studies can be performed Bacterial antigen studies can be performed

on urine and serum (mostly useful in cases on urine and serum (mostly useful in cases of pretreated meningitis)of pretreated meningitis)

Lumbar Lumbar PuncturePuncture

Do you need CT Do you need CT before LP??before LP??

When do you need CT When do you need CT before LP?before LP?

CT :CT :• Useful for identifying other lesions Useful for identifying other lesions

(abscesses, ICH, neoplasms).(abscesses, ICH, neoplasms).• May delay time to antibiotics (So, you May delay time to antibiotics (So, you

have to start empirical Abx before CT)have to start empirical Abx before CT)• Harmful Effects of radiation on the Harmful Effects of radiation on the

developing brain.developing brain.


Computed tomography of the Computed tomography of the head before lumbar puncture head before lumbar puncture

in adults with suspected in adults with suspected meningitismeningitis

Hasbun J. N Engl J Med. 345:24. Dec. 2001. 1727-1733Hasbun J. N Engl J Med. 345:24. Dec. 2001. 1727-1733


The clinical features that were The clinical features that were associated with an abnormal finding associated with an abnormal finding on CT of the head were:on CT of the head were:• Patients who are older than 60 years.Patients who are older than 60 years.• Patients who are immunocompromised.Patients who are immunocompromised.• Patients with known CNS lesions.Patients with known CNS lesions.• Patients who have had a seizure within 1 Patients who have had a seizure within 1

week of presentation.week of presentation.• Patients with abnormal level of Patients with abnormal level of

consciousness.consciousness.• Patients with focal findings on neurological Patients with focal findings on neurological

examination.examination.

Contraindications Contraindications to Lumbar to Lumbar PuncturePuncture

??

Absolute Absolute Contraindications to Contraindications to

LP:LP:• Unequal pressures between the Unequal pressures between the

supratentorial and infratentorial supratentorial and infratentorial compartments, inferred by characteristic compartments, inferred by characteristic findings on brain CT scan*:findings on brain CT scan*:

• Midline shiftMidline shift• Loss of suprachiasmatic and basilar cisternsLoss of suprachiasmatic and basilar cisterns• Posterior fossa massPosterior fossa mass• Loss of the superior cerebellar cisternLoss of the superior cerebellar cistern• Loss of the quadrigeminal plate cistern Loss of the quadrigeminal plate cistern

• Infected skin over the needle entry site.Infected skin over the needle entry site.* Contraindications to lumbar puncture as defined by computed cranial tomography. J Neurol Neurosurg Psychiatry. 1987 Aug;50(8):1071-4. Gower DJ, Baker AL, Bell WO, Ball MR.

Relative Relative contraindications to contraindications to

LP:LP:

• Cardiopulmonary instability.Cardiopulmonary instability.• Coagulopathy.Coagulopathy.• Signs of Signs of ↑ ↑ ICP.ICP.• Focal neurological signs.Focal neurological signs.

InvestigationsInvestigations

CSF studies:CSF studies:• Protein and glucose levelsProtein and glucose levels• Cell count and differentialCell count and differential• Gram stain and C/SGram stain and C/S• Latex antigen test of CSF for Latex antigen test of CSF for Haemophilus Haemophilus

influenzae, Streptococcus pneumoniae, Neisseria influenzae, Streptococcus pneumoniae, Neisseria meningitidis.meningitidis.

• Viral titers or cultures. Viral titers or cultures. • PCR; increasingly useful in CNS viral PCR; increasingly useful in CNS viral

infectionsinfections• ZN stain for AFB, TB culture & PCR.ZN stain for AFB, TB culture & PCR.• India ink stain, cryptococcal antigen & India ink stain, cryptococcal antigen &

fungal culture.fungal culture.

CSF FindingsCSF FindingsNormaNormall

BacteriBacterialal ViralViral TBTB

WBCWBC

<4 /<4 /μL60-70% Lymph

30-40% mono1-3% PMNs

100 - 60,000 100 - 60,000 //μL

PMNs predominate

20 – 1000 /20 – 1000 /μLPMNs

predominate early*,

Lymphoctes later

10 – 500 / 10 – 500 / μL PMNs early,

Lymphocytes and Mono later

ProteiProteinn

20 – 45 mg/dl20 – 45 mg/dl 80 – 500 mg/dl80 – 500 mg/dl 20 – 100 mg/dl20 – 100 mg/dl 100- 500 mg/dl100- 500 mg/dl

GlucosGlucosee

≥ ≥ 50 mg/dl or 50 mg/dl or 75% of blood 75% of blood

glucoseglucose

< 40 mg/dl or < 40 mg/dl or ↓ ↓ ↓ ↓ ratioratio

Normal but may Normal but may be depressedbe depressed

< 50 mg/dl, < 50 mg/dl, decreases with decreases with

timetime

OtherOtherGram StainGram Stain

Antigen testingAntigen testing

CultureCulture

PCRPCR

Viral cultureViral cultureAFBAFB

CultureCulture

Cerebrospinal Fluid Findings in Aseptic Versus Bacterial Meningitis

Barbara Negrini, Kelly J. Kelleher and Ellen R. Wald

Pediatrics 2000;105;316-319

Bacterial Bacterial Meningitis Scores Meningitis Scores

????

Performance of a predictive Performance of a predictive rule to distinguishrule to distinguish

bacterial and viral meningitisbacterial and viral meningitisJ Infect. J Infect. 2007 Apr2007 Apr ;54(4):328-36. Epub 2006 Aug 2 ;54(4):328-36. Epub 2006 Aug 2

Chavanet P, et al. Chavanet P, et al.

The aim of this study was to establish a simple scoring tool and compare it to other available decision making systems.

Main categories for bacterial etiology were,• Leucocytosis >15 giga,• CSF leucocytes count >1700 per ml,• CSF neutrophil percentage >80, • CSF protein >2.3 g/l• Glucose CSF/blood ratio <0.33

MeningitestMeningitest

• Value of ≥ 6 → BM in Adults

•Value of ≥ 2 → BM in Children

Performance of a predictive Performance of a predictive rule to distinguishrule to distinguish

bacterial and viral meningitisbacterial and viral meningitis

Clinical prediction rule for identifying Clinical prediction rule for identifying childrenchildren with cerebrospinal fluid with cerebrospinal fluid

pleocytosis at very low risk of bacterial pleocytosis at very low risk of bacterial meningitis.meningitis.

JAMA. JAMA. 2007 Jan2007 Jan 3;297(1):52-60. 3;297(1):52-60. Nigrovic LE, et alNigrovic LE, et al

BBacterial acterial MMeningitis eningitis SScore (BMS)*: core (BMS)*: • positive CSF Gram stain• CSF absolute neutrophil count (ANC) of at

least 1000 cells/μL• CSF protein of at least 80 mg/dL• peripheral blood ANC of at least 10 000

cells/μL• history of seizure before or at the time of

presentation* Patients are classified as very low risk if none of these

variables are present.

Of the 1714 patients categorized as Of the 1714 patients categorized as very low risk for bacterial meningitis very low risk for bacterial meningitis by the BMS, only 2 had bacterial by the BMS, only 2 had bacterial meningitis (sensitivity, 98.3%) meningitis (sensitivity, 98.3%) and both were younger than 2 months old..

Those with at least 1 risk factor (BMS ≥ 1)had a sensitivity of 100%, specificity of 61.5% in predicting BM. in predicting BM.

TreatmentTreatment

IDSA GUIDELINES 2004 IDSA GUIDELINES 2004 Practice Guidelines for the Practice Guidelines for the Management of Bacterial Management of Bacterial

Meningitis Meningitis

What about What about steroidssteroids

??

TreatmentTreatment

Corticosteroids:Corticosteroids:• Antibiotics used in the treatment of Antibiotics used in the treatment of

meningitis are bactericidal.meningitis are bactericidal.• Lysis of bacteria results in release of Lysis of bacteria results in release of

toxins which trigger an inflammatory toxins which trigger an inflammatory response.response.

• Anti-inflammatories could reduce Anti-inflammatories could reduce this response, resulting in less this response, resulting in less meningeal inflammation.meningeal inflammation.

Corticosteroids for Corticosteroids for acute bacterial acute bacterial

meningitis. meningitis. Cochrane Database Syst Rev. Cochrane Database Syst Rev. 2007 Jan2007 Jan 24; 24;

(1):CD004405(1):CD004405 van de Beek D, de Gans J, McIntyre P, Prasad K.van de Beek D, de Gans J, McIntyre P, Prasad K.

corticosteroids significantly reduced corticosteroids significantly reduced rates of mortality, severe hearing loss rates of mortality, severe hearing loss and neurological sequelae.and neurological sequelae.

In adults with community acquired bacterial meningitis, corticosteroid therapy should be administered in conjunction with the 1st antibiotic dose..

TreatmentTreatment

Isolation:Isolation:

• generally isolate cases of bacterial generally isolate cases of bacterial meningitis for up to 24 hours of meningitis for up to 24 hours of appropriate antibiotics.appropriate antibiotics.

• All patients with meningitis should All patients with meningitis should be reported to the health authority.be reported to the health authority.

TreatmentTreatment

ChemoProphylaxis for N. ChemoProphylaxis for N. Meningitidis:Meningitidis:• Indicated for those at increased risk; Indicated for those at increased risk; • Such as those who were in close contact Such as those who were in close contact

with patient for at least 4 hours during the with patient for at least 4 hours during the week before onset (e.g., house mates, week before onset (e.g., house mates, daycare center) daycare center)

• Or were exposed to patient's Or were exposed to patient's nasopharyngeal secretions (e.g., kissing, nasopharyngeal secretions (e.g., kissing, mouth-to-mouth resuscitation, intubation, mouth-to-mouth resuscitation, intubation, nasotracheal suctioning).nasotracheal suctioning).

TreatmentTreatment

Rifampin:Rifampin:• pediatric dose: pediatric dose:

• children <1 mo - 5 mg/kg q12h for 4 doseschildren <1 mo - 5 mg/kg q12h for 4 doses• children >1 mo - 10 mg/kg q12h for 4 children >1 mo - 10 mg/kg q12h for 4

dosesdoses

• adult dose: 600 mg PO bid for 4 doses adult dose: 600 mg PO bid for 4 doses Alternative: Alternative:

• CiprofloxacinCiprofloxacin (adults) 500 mg PO (adults) 500 mg PO single dose or single dose or

• If pregnant, If pregnant, CeftriaxoneCeftriaxone (250 mg) IM (250 mg) IM single dose.single dose.

TreatmentTreatment

ChemoProphylaxis for HiB:ChemoProphylaxis for HiB:• If any of the contacts is < 4 y/o and If any of the contacts is < 4 y/o and

not immunized for HiB, give not immunized for HiB, give prophylaxis to ALL contacts.prophylaxis to ALL contacts.

• Rifampin:Rifampin:• pediatric dose: 10 mg/kg PO q12h x 4 pediatric dose: 10 mg/kg PO q12h x 4

doses doses • adult dose: 600 mg PO q12h x 4 doses adult dose: 600 mg PO q12h x 4 doses

TreatmentTreatment

Aseptic Meningitis:Aseptic Meningitis:• Usually a benign, self-limited disease.Usually a benign, self-limited disease.• For most aseptic meningitis For most aseptic meningitis

(Enterovirus), treatment is primarily (Enterovirus), treatment is primarily supportive.supportive.

• If HSV infection is a possibility, acyclovir If HSV infection is a possibility, acyclovir should be added to the treatment should be added to the treatment regimen.regimen.

• Headache can be treated with NSAIDs Headache can be treated with NSAIDs or mild narcotics.or mild narcotics.

ComplicationsComplications

Acute complications:Acute complications:• Seizures (30%).Seizures (30%).• Syndrome of inappropriate Syndrome of inappropriate

antidiuretic hormone (SIADH) antidiuretic hormone (SIADH) secretion.secretion.

• Hemodynamic instability.Hemodynamic instability.• Subdural effusions.Subdural effusions.• Hydrocephalus.Hydrocephalus.• Focal neurologic deficits (10-15% of Focal neurologic deficits (10-15% of

patients).patients).

ComplicationsComplications

Chronic complications:Chronic complications:• Deafness (20-30% of affected Deafness (20-30% of affected

children with children with HiB HiB ).).• Seizure disorders.Seizure disorders.• Motor deficits.Motor deficits.• Language deficits.Language deficits.• Behavior disorders.Behavior disorders.• Mental retardation.Mental retardation.

SummarySummary

Provided by:

Emergency diagnosis and treatment of adult meningitis.

Michael T Fitch, Van de Beek. Lancet Infect Dis 2007 March; 7: 191–200

Algorithm for the management of patients with suspected community-acquired bacterial meningitis

Thank Thank YouYou

Meningitis “An Update” Saad A. Alsaleh. Objectives Introduction Introduction Classification...

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