Meningitis, Acute

Diagnosis

Indications for Testing

• Fever, headache, altered sensorium, and stiff neck

Laboratory Testing

• CDC meningitis overview
• 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 >300 mm 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 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 AFB cultures (when clinically indicated) require HIGH VOLUME taps (at least 10cc fluid [minimum 5cc for each test])
  • Viral culture from CSF not indicated
    • PCR testing for enterovirus, Epstein-Barr virus, herpes simplex virus, varicella-zoster virus, cytomegalovirus
• Blood cultures – may be positive in up to 2/3 of patients in Western countries
  • Not as sensitive if antibiotics administered 
• Other tests to consider
  • Malaria blood film – in areas where malaria is endemic
    • Has a negative predictive value of 98%
  • Rapid serum HIV antibody and plasma viral load testing – rule out acute HIV infection
    • Use 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

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 S. pneumoniae)

Differential Diagnosis

• Encephalitis
• 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
• Stroke
• Seizure disorder
• Febrile seizures in children
• Fabry disease
• Medications – numerous drugs can cause aseptic meningitis

Monitoring

Clinical Background

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, as nidus for development of infection)

Classification

• Viral (aseptic) – most common cause
  • Enterovirus – most common cause
  • Herpes simplex virus (HSV)
  • Arboviruses
    • West Nile virus
  • Mumps virus
  • Lymphocytic choriomeningitis
  • Other viruses – Epstein-Barr virus, cytomegalovirus, acute human immunodeficiency virus (HIV), human herpesvirus 6, 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 S. 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

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Enterovirus Detection by RT-PCR 0050249 Method: Qualitative Reverse Transcription Polymerase Chain Reaction	Identify enterovirus as an etiological agent of meningitis
Enterovirus and Parechovirus Detection by RT-PCR 2005730 Method: Qualitative Reverse Transcription Polymerase Chain Reaction	Identify enterovirus and parechovirus as etiological agents of meningitis
Herpes Simplex Virus by PCR 0060041 Method: Qualitative Polymerase Chain Reaction	Identify HSV as an etiological agent of meningitis
Cytomegalovirus by PCR 0060040 Method: Qualitative Polymerase Chain Reaction	Rapid test to identify CMV as an etiological agent of meningitis
Epstein-Barr Virus by PCR 0050246 Method: Qualitative Polymerase Chain Reaction	Identify EBV as an etiological agent of meningitis
Varicella-Zoster Virus by PCR 0060042 Method: Qualitative Polymerase Chain Reaction	Identify VZV as an etiological agent of meningitis
Acid-Fast Bacillus (AFB) Stain Only 0060151 Method: Auramine O Stain
Mycobacterium tuberculosis Amplified Detection , CSF 0060063 Method: Qualitative Transcription Mediated Amplification (Gen-Probe®)
Blastomyces dermatitidis Antigen EIA 2002926 Method: Quantitative Enzyme Immunoassay
Blastomyces dermatitidis Identification by DNA Probe 0062224 Method: Nucleic Acid Probe	Not from patient specimen
Blastomyces Antibody by CF 0050130 Method: Semi-Quantitative Complement Fixation
Blastomyces Antibody by ID 0050172 Method: Qualitative Immunodiffusion
Coccidioides immitis Identification by DNA Probe 0062225 Method: Nucleic Acid Probe	Not from patient specimen
Coccidioides Antibodies Panel, Serum by CF, ID, ELISA 0050588 Method: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Coccidioides Antibody by CF 0050170 Method: Semi-Quantitative Complement Fixation	Least sensitive in pulmonary cavitary disease
Coccidioides Antibody by ID 0050183 Method: Qualitative Immunodiffusion	Detect current or past infection
Coccidioides Antibody, IgG by ELISA 0050179 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Coccidioides Antibody, IgM by ELISA 0050178 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Cryptococcus Antigen, Serum 0050196 Method: Semi-quantitative Enzyme Immunoassay	Serum
Histoplasma Antigen Detection EIA, Urine 2006110 Method: Qualitative Enzyme Immunoassay
Histoplasma capsulatum Identification by DNA Probe 0062226 Method: Nucleic Acid Probe	Not from patient specimen
Histoplasma Antibodies by CF & ID 0050627 Method: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion
Histoplasma Antibody by ID 0050174 Method: Qualitative Immunodiffusion
Urinalysis, Complete 0020350 Method: Reflectance Spectrophotometry/Microscopy
Encephalitis Panel, CSF with Reflex to HSV Type 1 and 2 Glycoprotein G-Specific Ab, IgG 2001741 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody Semi-Quantitative Chemiluminescent Immunoassay
Encephalitis Panel, Serum with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG 2001742 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Chemiluminescent Immunoassay
Blood Culture, Fungal 0060070 Method: Continuous Monitoring Blood Culture/Identification