Meningitis, Acute

Indications for Testing

Fever, headache, altered sensorium and stiff neck

Laboratory Testing

Initial testing is nonspecific – CBC, electrolytes
- Normal WBC does not rule out meningitis
Cerebrospinal fluid (CSF) exam – necessary to determine presence of meningitis
- CSF opening pressure – limited value if normal; usually >300mm in bacterial but ≤300 in all others
- Microscopic exam – white count >1,000 cells/µL in >90% of patients with bacterial meningitis
  - Neutrophils (typically >80%) usually predominate in bacterial meningitis; monocytes predominate in viral and fungal meningitis
  - Exception is in patients who are immunocompromised
  - Immunocompromised patients and those with Listeria monocytogenes may have normal values
    - Listeria may also present with normal WBC counts and high protein CSF
  - Normal result does not exclude bacterial meningitis
- Protein – usually elevated (>200 mg/dL) in bacterial and fungal meningitis; usually <200 in viral
- Glucose – usually low (<10mg/dL) in bacterial meningitis and tuberculous disease; normal to minimally low in viral and fungal
- Gram stain – useful if positive
- Bacterial culture – gold standard for diagnosis
  - Anaerobic culture may be important for post-neurosurgical meningitis or shunt meningitis
- CSF antigen antibody testing, when appropriate (eg, pneumococcal antigen, dimorphic fungi serology, cryptococcal antigen)
- Fungal and/or AFB culture (when clinically indicated) requires a HIGH VOLUME tap (at least 10cc fluid [minimum 5cc for each test])
Viral culture from CSF not indicated (perform nucleic-acid amplification testing)
- PCR testing for enterovirus, EBV, HSV, VZV, CMV
Blood cultures – may be positive in up to 2/3 of patients in Western countries
- Not as sensitive if antibiotics administered
Malaria blood film – in areas where malaria is endemic, this has a negative predictive value of 98%
Rapid serum HIV antibody and plasma viral load testing – rule out acute HIV infection; used for patients with risk factors and aseptic meningitis
Urinalysis – may reveal urinary tract infection as etiology of bacteremia
Consider serologies
- Mumps, EBV – if clinical situation is compatible
- Neisseria meningitidis IgG – serotype species

Imaging Studies

If focal findings are present or patient is significantly immunocompromised, recommend CT/MRI prior to CSF tap
Chest x-ray – may be useful in diagnosing pneumonia as etiology (usually pneumococcus)

Differential Diagnosis

Connective tissue CNS disease
- Sjögren syndrome
- Systemic lupus erythematosus
Vasculitic CNS disease
- Behçet disease
- Wegener granulomatosis
Granulomatous CNS disease
- Sarcoidosis
Migraine headache
Malignant meningitis
- Carcinoma
- Lymphoma
  - B-cell
  - T-cell
- Leukemia
  - Acute lymphoblastic leukemia
  - Acute myeloid leukemia
Subarachnoid hemorrhage
Fabry disease
Medications (numerous drugs can cause aseptic meningitis)

IgG level pre- and 1 month post-vaccination to determine immunoglobulin deficiency
- Haemophilus influenzae
- Streptococcus pneumoniae
- Neisseria meningitidis

Meningitis is defined as inflammation of the leptomeninges, the tissues surrounding the brain and spinal cord. It is marked by an abnormal number of white blood cells in the cerebrospinal fluid (CSF). The focus of this review is on the infectious causes of acute meningitis.

Epidemiology

Incidence
- Bacterial – 4-6/100,000
- Viral – 11/100,000 in U.S.
Occurrence/transmission
- Hematogenous dissemination (bacteremia, viremia)
- Trauma – surgery, head trauma (basilar skull fracture, ie, trauma as nidus for development of infection)

Classification

Viral (aseptic) – most common cause
- Enterovirus – most common cause
- Herpes simplex virus (HSV)
- Arboviruses
  - West Nile virus (WNV)
- Mumps virus
- Lymphocytic choriomeningitis (LCM)
- Other viruses – Epstein-Barr virus (EBV), cytomegalovirus (CMV), acute human immunodeficiency virus (HIV), human herpesvirus 6 (HHV6), varicella-zoster virus (VZV), and adenoviruses
Bacterial
- Neisseria meningitidis
- Streptococcus pneumoniae
- Haemophilus influenzae
- Listeria monocytogenes
- Escherichia coli
- Beta-hemolytic group B streptococcus
- Mycobacterial – Mycobacterium tuberculosis
Fungal
- Blastomyces dermatitidis
- Cryptococcus neoformans
- Histoplasma capsulatum
- Coccidioides immitis
Parasites
- Amoeba – Acanthamoeba and Naegleria
- Angiostrongylus cantonensis
Spirochetes
- Treponema pallidum
- Borrelia burgdorferi
Tickborne illnesses
- Rickettsia rickettsii (Rocky Mountain spotted fever)
- Ehrlichia chaffeensis
- Anaplasma phagocytophilum

Risk Factors

Advanced age
Male sex
Low socioeconomic status
Crowded living conditions
African American ethnicity
Dural defects
Intravenous drug abuse
Immunosuppression (eg HIV, connective tissue diseases, malignancy)
Indwelling shunts
Recent neurologic surgery

Clinical Presentation

Headache
Fever
Meningismus, nuchal rigidity, altered sensorium, seizures, photophobia
- Kernig sign – resistance to passive extension of the knee when the hip is flexed at 90%
- Brudzinski sign – spontaneous flexion of hips and knees on passive flexion of the neck
Nausea, emesis
Focal neurologic deficits, hemiparesis
Rash – VZV, meningococcus, Rocky Mountain spotted fever, ehrlichiosis
Complications
- Shock
- Disseminated intravascular coagulation
- Focal permanent neurologic deficits
  - Deafness, blindness, paresis
- Hydrocephalus
- Central nervous system abscess
- Seizure disorder
- Recurrent meningitis
  - Congenital anatomical defects
  - Neurogenic cysts
  - Asplenia
  - Congenital immunodeficiencies (eg, complement deficiency)
  - Acquired immunodeficiencies (eg, HIV)
  - Mollaret meningitis (caused by HSV)

Treatment

Immediate institution of antimicrobial therapy if bacterial, tuberculosis, or fungal meningitis is suspected
For bacterial – cover Streptococcal pneumonia, N. meningitidis, H. influenzae
For focal neurologic causes – cover HSV until studies rule out HSV

Prevention

Viral – mumps vaccination
Bacterial
- H. influenzae vaccination in childhood
- S. pneumoniae vaccination in childhood
  - Conjugate vaccine for infants, polysaccharide vaccine for other at-risk groups
- N. meningitidis vaccination in children 11-18 years (if vaccinated between 11 and 15 years, recommend booster), freshmen entering college, complement deficient patients, asplenic patients
  - Chemoprophylaxis for close contacts of patients with N. meningitidis

Tests generally appear in the order most useful for common clinical situations

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

May be helpful in differentiating bacterial from viral etiology

Test name: Electrolyte Panel

ARUP #: 0020410

Methodology: Quantitative Ion-Selective Electrode/Enzymatic

Use:

Useful in assessing metabolic derangement as cause of altered consciousness

Test name: CSF Bacterial Culture (Includes Gram Stain 0060101)

ARUP #: 0060106

Methodology: Standard reference procedures for bacterial stain, aerobic culture, and identification

Use:

Identify organism causing meningitis

Test name: Glucose, Plasma or Serum

ARUP #: 0020024

Methodology: Quantitative Enzymatic

Use:

Useful in assessing metabolic derangement as cause of altered consciousness

Test name: Cell Count, CSF

ARUP #: 0095018

Methodology: Cell Count/Differential

Use:

Aids in differentiating bacterial from viral meningitis

Test name: Glucose, CSF

ARUP #: 0020515

Methodology: Enzymatic

Use:

May be helpful in differentiating bacterial from viral etiology

Usually low (<10mg/dL) in bacterial meningitis and tuberculous disease

Test name: Protein, Total, CSF

ARUP #: 0020514

Methodology: Reflectance Spectrophotometry

Use:

May be helpful in differentiating bacterial from viral etiology

Test name: Blood Culture

ARUP #: 0060102

Methodology: Continuous Monitoring Blood Culture/Identification

Use:

Identify possible source of meningitis

Limitations:

Testing is limited to the University of Utah Health Sciences Center only

Test name: Fungal Culture

ARUP #: 0060149

Methodology: Standard reference procedures for fungal culture. Standard reference procedures for identification and/or ITS rDNA Sequencing. DNA probes available for Histoplasma, Coccidioides, and Blastomyces

Use:

May identify fungal causes or help identify organism responsible for meningitis

Limitations:

Need 5cc fluid to culture for fungus

Test name: Enterovirus Detection by RT-PCR

ARUP #: 0050249

Methodology: Qualitative Reverse Transcription Polymerase Chain Reaction

Use:

Identify enterovirus as an etiological agent of meningitis

Test name: Epstein-Barr Virus by PCR

ARUP #: 0050246

Methodology: Qualitative Polymerase Chain Reaction

Use:

Identify EBV as an etiological agent of meningitis

Test name: Herpes Simplex Virus by PCR

ARUP #: 0060041

Methodology: Qualitative Polymerase Chain Reaction

Use:

Identify HSV as an etiological agent of meningitis

Test name: Varicella-Zoster Virus by PCR

ARUP #: 0060042

Methodology: Qualitative Polymerase Chain Reaction

Use:

Identify VZV as an etiological agent of meningitis

Test name: Cytomegalovirus by PCR

ARUP #: 0060040

Methodology: Qualitative Polymerase Chain Reaction

Use:

Rapid test to identify CMV as an etiological agent of meningitis

Test name: AFB Culture (Includes AFB Stain 0060151)

ARUP #: 0060152

Methodology: Standard reference procedures for stain and culture. Identification tests of AFB are ordered and billed separately. DNA probes are available for M. tuberculosis complex and M. avium-intracellulare complex as indicated. DNA sequencing and other molecular techniques are used for identification. For drug susceptibilities, refer to Antimicrobial Susceptibility - AFB Mycobacteria (ARUP test code 0060217).

Use:

Identify M. tuberculosis as etiological agent of meningitis

Limitations:

Need 5cc fluid (sputum, CSF, urine, body fluid, tissue or gastric aspirate) for AFB culture

Test name: Streptococcus pneumoniae Antigen, CSF

ARUP #: 0061162

Methodology: Qualitative Immunochromatographic Assay

Use:

Identify presence of Streptococcus pneumoniae

Limitations:

False positives may occur because of cross-reactivity with other members of S. mitis group; clinical correlation recommended

Patients who have received the S. pneumoniae vaccines may test positive in the 48 hours following vaccination; avoid testing within 5 days of receiving vaccination

Samples from patients taking antibiotics >24 hours may show a false-negative result.

Test name: Wright Stain

ARUP #:

Methodology:

Use:

Identify presence of Naegleria and Acanthamoeba in CSF specimen

Test name: Meningoencephalitis Panel, CSF with Reflex to HSV Type 1 & Type 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001765

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Use:

Evaluate for presence of meningitis

Panel components include California encephalitis, Eastern equine encephalitis, St. Louis equine encephalitis, Western equine encephalitis, WNV, measles, mumps, VZV, HSV types 1 and 2, and LCM antibodies

Test name: Meningoencephalitis Panel, Serum with Reflex to HSV Type 1 & Type 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001764

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Chemiluminescent Immunoassay

Use:

Evaluate for presence of meningitis

Panel components include California encephalitis, Eastern equine encephalitis, St. Louis equine encephalitis, Western equine encephalitis, WNV, measles, mumps, VZV, HSV types 1 and 2, and LCM antibodies

Test name: Neisseria meningitidis Tetravalent Antibodies (Serogroups A, C, W-135 & Y), IgG

ARUP #: 2001603

Methodology: Quantitative Multi-Analyte Fluorescent Detection

Use:

Serotype species

Determine pre- and post-vaccination status

Test name: Acanthamoeba and Naegleria Culture

ARUP #: 0060245

Methodology: Qualitative Culture/Microscopic Identification

Use:

Identify Acanthamoeba or Naegleria as an etiological agent of meningitis

Test name: West Nile Virus Antibodies, IgG & IgM by ELISA, CSF

ARUP #: 0050228

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Use:

Identify WNV as an etiological agent of meningitis

Test name: Arbovirus Antibodies, IgM, CSF

ARUP #: 2001595

Methodology: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Use:

Identify arbovirus as an etiological agent of meningitis

Test name: Ehrlichia and Anaplasma Species by Real-Time PCR

ARUP #: 2003078

Methodology: Real-Time Polymerase Chain Reaction/DNA Probe Hybridization

Use:

Identify Ehrlichia or Anaplasma as etiological agent of meningitis

Test name: Lymphocytic Choriomeningitis (LCM) Virus Antibodies, IgG & IgM, CSF

ARUP #: 2001628

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Use:

Identify LCM as an etiological agent of meningitis

Test name: Cryptococcus Antigen, CSF

ARUP #: 0050195

Methodology: Semi-quantitative Enzyme Immunoassay

Use:

Identify Cryptococcus as an etiological agent of meningitis

Test name: Coccidioides Antibodies Panel, CSF by CF, ID, ELISA

ARUP #: 0050710

Methodology: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion/Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Use:

Detect both IgG and IgM antibodies in acute and convalescent samples

Confirm coccidioidal disease as an etiological agent of meningitis

Follow-up:

For equivocal results, repeat of testing in 10-14 days may be helpful

Test name: Blastomyces Antibodies by CF & ID

ARUP #: 0050626

Methodology: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion

Use:

Identify Blastomyces as an etiological agent of meningitis

Test name: Histoplasma Antigen by EIA, Serum

ARUP #: 0092522

Methodology: Semi-quantitative Enzyme Immunoassay

Use:

Diagnose and monitor response to therapy in Histoplasma-caused disease

Limitations:

Rarely positive in chronic cases

Additional Tests Available

Test name: AFB Stain Only

ARUP #: 0060151

Methodology: Auramine O Stain

Comments:

Test name: Mycobacterium tuberculosis Amplified Detection , CSF

ARUP #: 0060063

Methodology: Qualitative Transcription Mediated Amplification (Gen-Probe®)

Comments:

Test name: Blastomyces dermatitidis Antigen EIA

ARUP #: 2002926

Methodology: Quantitative Enzyme Immunoassay

Comments:

Test name: Blastomyces dermatitidis Identification by DNA Probe

ARUP #: 0062224

Methodology: Nucleic Acid Probe

Comments:

Not from patient specimen

Test name: Blastomyces Antibody by CF

ARUP #: 0050130

Methodology: Semi-Quantitative Complement Fixation

Comments:

Test name: Blastomyces Antibody by ID

ARUP #: 0050172

Methodology: Qualitative Immunodiffusion

Comments:

Test name: Coccidioides immitis Identification by DNA Probe

ARUP #: 0062225

Methodology: Nucleic Acid Probe

Comments:

Not from patient specimen

Test name: Coccidioides Antibodies Panel, Serum by CF, ID, ELISA

ARUP #: 0050588

Methodology: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion/Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Comments:

Test name: Coccidioides Antibody by CF

ARUP #: 0050170

Methodology: Semi-Quantitative Complement Fixation

Comments:

Least sensitive in pulmonary cavitary disease

Test name: Coccidioides Antibody by ID

ARUP #: 0050183

Methodology: Qualitative Immunodiffusion

Comments:

Test name: Coccidioides Antibody, IgG by ELISA

ARUP #: 0050179

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Comments:

Test name: Coccidioides Antibody, IgM by ELISA

ARUP #: 0050178

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Comments:

Test name: Cryptococcus Antigen, Serum

ARUP #: 0050196

Methodology: Semi-quantitative Enzyme Immunoassay

Comments:

Serum

Test name: Histoplasma Antigen Detection EIA, Urine

ARUP #: 2006110

Methodology: Qualitative Enzyme Immunoassay

Comments:

Test name: Histoplasma capsulatum Identification by DNA Probe

ARUP #: 0062226

Methodology: Nucleic Acid Probe

Comments:

Not from patient specimen

Test name: Histoplasma Antibodies by CF & ID

ARUP #: 0050627

Methodology: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion

Comments:

Test name: Histoplasma Antibody by ID

ARUP #: 0050174

Methodology: Qualitative Immunodiffusion

Comments:

Test name: Urinalysis, Complete

ARUP #: 0020350

Methodology: Reflective Photometry/Microscopic by Yellow IRIS

Comments:

Test name: Encephalitis Panel, CSF with Reflex to HSV Type 1 & 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001741

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Encephalitis Panel, Serum with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001742

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Blood Culture, Fungal

ARUP #: 0060070

Methodology: BACTEC® Continuous Monitoring System.
Standard reference procedures for identification and/or DNA Sequencing

Comments:

General

ARUP Institute for Clinical and Experimental Pathology®

Comprehensive Review: March 2011
Last Update: January 2012

Acanthamoeba and Naegleria

Central Nervous System Tumors

CSF Leak

Ehrlichiosis and Colorado Tick Fever

Haemophilus influenzae

Herpes Simplex Virus

Herpesvirus 6

Leptospira Species

Listeria monocytogenes

Lymphocytic Choriomeningitis

Streptococcal Disease, Group B

Streptococcus pneumoniae

Varicella-Zoster Virus