Infectious Encephalitis

Encephalitis is a devastating neurologic syndrome that is characterized by inflammation of the brain parenchyma. While infectious encephalitis is most often identified, the cause remains unknown in up to 50% of cases. An acute clinical presentation may suggest more virulent viruses and bacteria, while a subacute presentation is more often associated with indolent bacteria, fungi, parasites, and autoimmune and paraneoplastic causes. More than 90% of viral encephalitis is caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), and enteroviruses (Venkatesan, 2014), with typical bacterial causes of cerebritis and abscesses consisting of polymicrobial streptococci, gram-negative bacilli, and Staphylococcus aureus infections. Early recognition and treatment for HSV, bacterial, Plasmodium falciparum, and rabies infections are critical and potentially life saving. Diagnosis requires a combination of clinical, laboratory, and neuroimaging findings (Venkatesan, 2014).

Tabs Content

Clinical Overview

Diagnosis

Indications for Testing

Focal neurologic signs
Confusion, altered mental status, or behavioral changes
Fever
Seizure

Criteria for Diagnosis

International Encephalitis Consortium’s 2013 Diagnostic Criteria for Encephalitis
Major Criterion (required)	Minor Criterion (2 required for possible encephalitis, ≥3 required for probable or confirmed encephalitis)
Patient presenting for medical attention with altered mental status (defined as decreased or altered level of consciousness, lethargy, or personality change) lasting ≥24 hours with no alternative cause identified	Documented fever ≥38° C (100.4° F) within the 72 hours before or after presentation Generalized or partial seizures not fully attributable to a preexisting seizure disorder New onset of focal neurologic findings CSF WBC count ≥5/mm³ Abnormality of brain parenchyma on neuroimaging suggestive of encephalitis that is either new from prior studies or appears acute in onset Abnormality on EEG that is consistent with encephalitis and not attributable to another cause
CSF, cerebrospinal fluid; EEG, electroencephalography; WBC, white blood cell Source: Venkatesan, 2013

Laboratory Testing

Initial, nonspecific testing
- CBC – usually not helpful
  - Leukocytosis suggests a bacterial etiology
  - Relative lymphocytosis suggests a viral etiology
- Electrolyte panel, liver function studies – useful to rule out metabolic encephalopathy
  - Elevated transaminases – consider tickborne disease testing if appropriate clinical history
- C-reactive protein (CRP)
  - Indicated to detect inflammatory process
  - If CRP not available, order erythrocyte sedimentation rate (ESR)
- Non-CSF cultures – relatively poor sensitivity
  - Blood – two to three sets from separate venipuncture sites prior to the administration of antibiotics
  - Other site cultures may be helpful based on other symptoms suggesting infection – sputum, urine, pleural/peritoneal/synovial fluid, stool, skin lesions
Routine studies for encephalitis workup
- CSF analysis – critical for diagnosis unless contraindicated (Zunt, Infectious Diseases Society of America [IDSA], 2008; Venkatesan, 2014)
  - Glucose – collect concomitantly for comparison
    - Low or normal glucose – suggests bacterial, fungal, or mycobacterial infection
  - Protein
  - Gram stain and bacterial culture
  - Nucleic acid amplification testing (eg, polymerase chain reaction [PCR])
    - HSV 1/2, enterovirus, and VZV
      - Most commonly identified etiologic agents in acute encephalitis (Venkatesan, 2014)
      - HSV – should be performed on all CSF specimens in patients with encephalitis (Zunt, IDSA, 2008)
        Consider retesting in 3-7 days if signs and symptoms suggest high probability or if temporal lobe localization on neuroimaging (Zunt, IDSA, 2008)
      - Enterovirus – more commonly positive in meningitis
  - Serology – viral IgM antibodies in CSF specimen considered diagnostic for many diseases (eg, primary VZV and many arboviruses) (Zunt, IDSA, 2008)
  - Other tests, if indicated – Cryptococcal antigen or India ink staining
  - Venereal Disease Research Laboratory (VDRL) testing – syphilis
- Routine blood culture
- Serum (Venkatesan, 2014)
  - HIV serology (consider RNA)
  - Treponemal testing – rapid plasma reagin (RPR), specific treponemal test
Examples of conditional studies – for more comprehensive listing, refer to 2008 IDSA guidelines, or Venkatensan, 2014
- Host factors (eg, immunocompromised) – CMV or HHV6/7 PCR testing, West Nile virus
- Geographic factors
  - North America – geographically appropriate arboviruses
  - Africa – malaria, dengue
  - Asia – Japanese encephalitis virus
  - Europe – tickborne encephalitis virus
- Seasonal factors
  - Tick exposure (consider tickborne disease testing), animal bite (eg, if bat, consider rabies testing), swimming or diving in warm freshwater (consider Naegleria fowleri testing)

Histology

Brain biopsy – not routinely recommended, but may be indicated if patient continues to decline and no etiology has been established (Zunt, IDSA, 2008)

Imaging Studies

Magnetic resonance imaging (MRI) – most sensitive neuroimaging test to evaluate patients with encephalitis (Zunt, IDSA, 2008)
- Evaluate for abscess, tumor, subdural or subarachnoid bleed, other structural lesions, demyelination, and cerebral edema
- Computed tomography (CT), with and without contrast enhancement, should be used only if MRI is not available (Zunt, IDSA, 2008)

Other Tests

EEG – may demonstrate seizure activity; most useful in HSV

Differential Diagnosis (Noninfectious)

Vascular disease
- Stroke
- Subarachnoid or subdural hemorrhage
Autoimmune or paraneoplastic
- Autoimmune central nervous system (CNS) disease (most commonly systemic lupus erythematosus [SLE])
- CNS vasculitis
- Anti-NMDA receptor syndrome
- Paraneoplastic neurological syndromes
Toxin-induced disorder
- Drug overdose
- Alcohol
- Adverse drug reactions (eg, cyclosporine)
Metabolic derangement
- Metabolic acidosis
- Hyperglycemia/hypoglycemia
- Hepatic encephalitis
- Renal encephalitis
Malignant disease
- Primary tumor
- Metastatic tumors
- Paraneoplastic syndromes
Neurodegenerative disease
- Frontotemporal dementia
- Prion disease (eg, Creutzfeldt-Jakob)
Demyelinating disease
- Multiple sclerosis
- Neuromyelitis optica
Endocrine disease
- Addisonian crisis
- Hyperthyroid storm
Psychiatric disorder
- Psychosis
- Catatonia

Background

Epidemiology

Incidence – 0.7-13.8/100,000 for all ages (Solomon, 2012)
- Increased incidence (10.5-13.8/100,000) in children
Age – peaks at >65 years and <1 year
Sex – M>F (minimal)

Organisms

Examples of typical viral, bacterial, parasitic, fungal organisms

Examples of Typical Viral, Bacterial, Parasitic, Fungal Organisms
Viral	Bacterial	Parasitic	Fungal
Adenovirus Arbovirus Cytomegalovirus Enterovirus Epstein-Barr virus Human herpesvirus 6 and 7 Human immunodeficiency virus Influenza virus Lymphocytic choriomeningitis Measles virus Mumps virus Rabies virus Rubella virus Tickborne viruses Varicella-Zoster virus	Actinomyces odontolyticus Bartonella spp Borrelia burgdorferi, B. miyamotoi Brucella spp Chlamydia spp Legionella spp Leptospira spp Listeria monocytogenes Mycobacterium tuberculosis Mycoplasma pneumoniae Nocardia spp Rickettsia spp Treponema pallidum Tropheryma whipplei	Acanthamoeba spp Balamuthia mandrillaris Echinococcus multilocularis Naegleria fowleri Plasmodium falciparum Toxoplasma gondii Trypanosoma spp	Blastomyces dermatitidis Candida spp Cryptococcus neoformans Histoplasma capsulatum

Clinical Presentation

Constitutional – fever, fatigue, myalgias
Neurologic – headache, altered consciousness, focal neurologic findings, seizures, coma
Dermatologic – skin rashes (eg, Rickettsia spp), skin lesions (VZV, HSV), bite-site paresthesias (rabies virus)
Gastroenterologic – nausea, emesis (enterovirus)
Pulmonary – cough, dyspnea (Mycobacterium spp, Mycoplasma spp)

ARUP Lab Tests

Detect cytomegalovirus (CMV), Epstein-Barr virus (EBV), HSV, or VZV as etiological agents of meningoencephalitis

Viral Meningoencephalitis Panel by PCR, Cerebrospinal Fluid 2007062

Method: Qualitative Polymerase Chain Reaction

Use to rapidly detect a panel of common viruses, bacteria, and fungi associated with meningitis and encephalitis

Do NOT use as a replacement for CSF bacterial and/or fungal culture and cryptococcal antigen testing for at-risk patients

A negative result does not exclude a diagnosis of meningitis or encephalitis due to infection

Meningitis/Encephalitis Panel by PCR 2013305

Method: Qualitative Polymerase Chain Reaction

Panel includes Cryptococcus neoformans/gattii, CMV, enterovirus, Escherichia coli K1, Haemophilus influenzae, HSV-1, HSV-2, human herpesvirus 6 (HHV-6), human parechovirus, Listeria monocytogenes, Neisseria meningitidis, Streptococcus agalactiae, Streptococcus pneumoniae, and VZV

Identify bacteria in CSF

Cerebrospinal Fluid (CSF) Culture and Gram Stain 0060106

Method: Stain/Culture/Identification

Aid in differentiation of viral from bacterial etiology

Glucose, CSF 0020515

Method: Enzymatic

Protein, Total, CSF 0020514

Method: Reflectance Spectrophotometry

Detect presence of bacteria in blood

Important information Limited to the University of Utah Health Sciences Center only

Blood Culture 0060102

Method: Continuous Monitoring Blood Culture/Identification

Identify Cryptococcus as an etiological agent of meningitis

CAP requires confirmation by culture for this test

When test is ordered by the University of Utah Hospital, Huntsman Cancer Hospital, or VA Hospital of SLC, CSF culture will be ordered automatically; other clients should order culture separately

Cryptococcus Antigen, CSF 0050195

Method: Semi-Quantitative Enzyme Immunoassay

Related Tests

Leukocytosis may indicate bacterial etiology; relative lymphocytosis may suggest viral etiology

CBC with Platelet Count and Automated Differential 0040003

Method: Automated Cell Count/Differential

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)

C-Reactive Protein 0050180

Method: Quantitative Immunoturbidimetry

Nonspecific test used to detect inflammation associated with infections, cancers, and autoimmune diseases

Sedimentation Rate, Westergren (ESR) 0040325

Method: Visual Identification

Gold standard; most sensitive test for diagnosing mycobacteria

The laboratory should be notified when the presence of Mycobacterium genavense is suspected, as this organism will not grow on media routinely used for Mycobacterium isolation

Susceptibility testing will be performed on organisms isolated from a sterile source and for isolates of M. chelonae, M. abscesses, M. fortuitum complex, M. immunogenum, M. mucogenicum; susceptibility testing will be performed by request only on M. kansaii and M. marinum; susceptibility testing of M. gordonae is inappropriate

Acid-Fast Bacillus (AFB) Culture and AFB Stain 0060152

Method: Stain/Culture /Identification/Susceptibility

Use to detect aerobic actinomycetes (Nocardia and Gordonia spp, etc) in clinical specimens

Acid Fast Stain, Partial or Modified (for Nocardia spp.) 0060325

Method: Stain/Microscopy

Diagnose anaerobic bacterial infections

Anaerobe Culture and Gram Stain 0060143

Method: Stain/Culture/Identification

Gold standard test to diagnose fungi as agent of infection

Fungal Culture 0060149

Method: Culture/Identification

Gold standard test to diagnose fungi as agent of infection in blood

Blood Culture, Fungal 0060070

Method: Continuous Monitoring Blood Culture/Identification

Comprehensive panel for the evaluation of paraneoplastic and neuromuscular junction disorders, and/or encephalitis, in the presence or absence of malignancy

Autoimmune Neurologic Disease Reflexive Panel, Serum 2013944

Method: Semi-Quantitative Indirect Fluorescent Antibody/Qualitative Immunoblot/Quantitative Radioimmunoassay/Semi-quantitative Enzyme-Linked Immunosorbent Assay

Panel includes Purkinje cell (PCCA) antibody and neuronal nuclear (ANNA) antibody IgG by indirect fluorescent antibody (IFA) with reflex to titer and immunoblot (Hu, Ri, Yo); amphiphysin antibody IgG; CV2.1 antibody IgG by IFA with reflex to titer; NDMA receptor antibody, IgG with reflex to titer; glutamic acid decarboxylase (GAD) antibody; voltage-gated potassium channel (VGKC) antibody; aquaporin-4 receptor antibody; aquaporin-4 receptor antibody, IgG by IFA with reflex to titer; leucine-rich, glioma-inactivated protein 1 antibody, IgG with reflex to titer; contactin-associated protein-2 antibody, IgG with reflex to titer; N-type voltage-gated calcium channel (VGCC) antibody; P/Q type VGCC antibody; acetylcholine receptor binding antibody with reflex to acetylcholine receptor modulating antibody; titin antibody; and striated muscled antibody

Detect Acanthamoeba spp and N. fowleri in various specimen types

Acanthamoeba and Naegleria Culture 0060245

Method: Qualitative Culture/Microscopy

Useful if Giemsa stain is negative, but high suspicion of babesiosis exists

Will not detect Babesia duncani or strain MO-1

Babesia microti Antibodies, IgG and IgM by IFA 0093048

Method: Semi-Quantitative Indirect Fluorescent Antibody

Detect Bartonella species in blood, CSF, or tissue

Bartonella Species by PCR 0093057

Method: Qualitative Polymerase Chain Reaction

Use in conjunction with positive serologic testing for the workup of suspected acute Lyme neuroborreliosis

Do not order in the absence of clinical symptom

Borrelia burgdorferi Antibodies, IgG and IgM by Immunoblot (CSF) 0055260

Method: Qualitative Immunoblot

Preferred reflex test to detect Lyme disease in individuals with ≤4 weeks of clinical symptoms or exposure to tick

Positive/equivocal screen confirmed by immunoblot

Borrelia burgdorferi Antibodies, Total by ELISA with Reflex to IgG and IgM by Immunoblot (Early Disease) 0050267

Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunoblot

Reflex pattern: if enzyme-linked immunosorbent assay (ELISA) result is 1.00 LIV or greater, then IgG and IgM immunoblot will be added

Not a first-line test for Lyme disease; may be useful if strong suspicion of Lyme disease persists in spite of persistent negative serologic testing

Borrelia Species by PCR (Lyme Disease) 0055570

Method: Qualitative Polymerase Chain Reaction

Detect C. pneumoniae in bronchoalveolar lavage (BAL), nasal wash, nasopharyngeal swab, or pleural fluid

Chlamydia pneumoniae by PCR 0060715

Method: Qualitative Polymerase Chain Reaction

Identify Cryptococcus neoformans as the infectious agent of invasive cryptococcal disease

Cryptococcus Antigen, Serum 0050196

Method: Semi-quantitative Enzyme Immunoassay

Aid in discriminating between current and past CMV infection in immunocompetent individuals

Cytomegalovirus Antibodies, IgG and IgM 0050622

Method: Semi-Quantitative Chemiluminescent Immunoassay

Detects CMV but does not quantify viral load; potentially useful for specimen types other than blood

CMV by quantitative PCR on plasma is preferred for most clinical indications

Cytomegalovirus by Qualitative PCR 0060040

Method: Qualitative Polymerase Chain Reaction

Adjunct to other diagnostic tests (eg, imaging) for echinococcosis

Patient's travel history is necessary to aid in test interpretation

Echinococcus Antibody, IgG 2007220

Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Diagnose infection from E. chaffeensis

Ehrlichia chaffeensis Antibodies, IgG & IgM by IFA 0051002

Method: Semi-Quantitative Indirect Fluorescent Antibody

Detect enterovirus in blood, CSF, or nasopharyngeal specimens

Enterovirus by PCR 0050249

Method: Qualitative Polymerase Chain Reaction

Aid in diagnosis of primary EBV infectious mononucleosis after a suspected false-negative heterophile antibody (Monospot) test

Epstein-Barr Virus Antibody Panel I 0050600

Method: Semi-Quantitative Chemiluminescent Immunoassay

Panel includes EBV antibody to viral capsid antigen, IgG and IgM; nuclear antigen, IgG; early D antigen (EA-D), IgG

Aid in determining past or present EBV infection as well as susceptibility to future EBV infection

May be used in conjunction with EBV nuclear antigen to diagnose primary EBV infectious mononucleosis

Epstein-Barr Virus Antibody Panel II 0050602

Method: Semi-Quantitative Chemiluminescent Immunoassay

Panel includes EBV antibody to viral capsid antigen, IgG and IgM

Do not use for diagnosis of infectious mononucleosis

Order to detect EBV in individuals suspected of having EBV-related disease

Epstein-Barr Virus by PCR 0050246

Method: Qualitative Polymerase Chain Reaction

Preferred test for detecting antibodies during acute or convalescent phase

Convalescent sera may be required for diagnosis

Francisella tularensis Antibodies, IgG and IgM 2005350

Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Detect antibodies during convalescent phase

Convalescent sera may be required for diagnosis

Francisella tularensis Antibody, IgG 2005353

Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Detect antibodies during convalescent phase

Convalescent sera may be required for diagnosis

Francisella tularensis Antibody, IgM 2005354

Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Traditional gold standard test for identifying acute HSV infection in active lesions (eg, vesicles, ulcers, inflamed mucous membranes)

Molecular testing is generally preferred (refer to HSV by PCR)

Herpes Simplex Virus Culture 0065005

Method: Cell Culture/Immunoassay

Preferred test for detecting HSV infection in CSF, neonates, or when rapid diagnostic test for suspected HSV infection is necessary

Herpes Simplex Virus by PCR 0060041

Method: Qualitative Polymerase Chain Reaction

Recommend testing in conjunction with the combined complement fixation and immunodiffusion antibody and urine galactomannan antigen tests

Histoplasma Antigen Quantitative by EIA, Serum 0092522

Method: Quantitative Enzyme Immunoassay

Detect and quantify HHV6 subtypes A and B in immunocompromised patients

A negative result (<3.0 log copies/mL or <1,000 copies/mL) does not rule out the presence of PCR inhibitors in the patient specimen or HHV6 DNA in concentrations below the level of detection of the test

Human Herpesvirus 6 (HHV-6A and HHV-6B) by Quantitative PCR 0060071

Method: Quantitative Polymerase Chain Reaction

2014 CDC Recommended Algorithm for Laboratory Diagnosis of HIV infection

Fourth generation test screens for HIV-1 p24 antigen and antibodies to HIV-1 (groups M and O) and HIV-2

Not available to New York clients; refer to New York HIV combo antigen/antibody (HIV-1/O/2) reflexive panel

Human Immunodeficiency Virus (HIV) Combo Antigen/Antibody (HIV-1/O/2) by CIA, Reflexive Panel 2012674

Method: Qualitative Chemiluminescent Immunoassay/Qualitative Immunoassay/Quantitative Transcription-Mediated Amplification

Reflex pattern: repeatedly reactive HIV-1, 2 antigen/antibody screening results are confirmed with an HIV-1/ HIV-2 antibody differentiation test; negative or indeterminate results for HIV-1, 2 antibody differentiation are confirmed with a quantitative NAAT test

Human Immunodeficiency Virus 1 (HIV-1) by Qualitative Transcription-Mediated Amplification (TMA) 2014234

Method: Qualitative Transcription-Mediated Amplification

Detect Legionella species

Legionella Species by Qualitative PCR 2010125

Method: Qualitative Polymerase Chain Reaction

May provide definitive diagnosis, but sensitivity is low and culture may take several weeks to yield result

Leptospira Culture 0060158

Method: Culture

Listeria Antibody, Serum by CF 0099529

Method: Semi-Quantitative Complement Fixation

Aid in the diagnosis of lymphocytic choriomeningitis (LCM) viral infection

Lymphocytic Choriomeningitis (LCM) Virus Antibodies, IgG & IgM 2001635

Method: Semi-Quantitative Indirect Fluorescent Antibody

Aid in the diagnosis of LCM viral infection in CNS

Lymphocytic Choriomeningitis (LCM) Virus Antibodies, IgG & IgM, CSF 2001628

Method: Semi-Quantitative Indirect Fluorescent Antibody

Culture test for detecting measles virus in specimens other than CSF

Measles (Rubeola) Virus Culture 0065055

Method: Cell Culture/Immunofluorescence

Aid in the diagnosis of measles infection

Test may not be helpful in patients who have recently received an MMR vaccination

Measles (Rubeola) Antibodies, IgG and IgM 0050375

Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay /Semi-Quantitative Chemiluminescent Immunoassay

Aid in the diagnosis of measles infection

Test may not be helpful in patients who have recently received an MMR vaccination

Mumps Virus Antibody, IgM 0099589

Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Not recommended

Mumps Virus Antibody IgM, CSF 0054443

Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Detect M. pneumoniae bacteria

Mycoplasma pneumoniae by PCR 0060256

Method: Qualitative Polymerase Chain Reaction

Confirm diagnosis of anti-NMDAR encephalitis

May be used in monitoring treatment response in individuals who are antibody positive

N-methyl-D-Aspartate Receptor Antibody, IgG, Serum with Reflex to Titer 2004221

Method: Semi-Quantitative Indirect Fluorescent Antibody

Reflex pattern: if NMDA antibody IgG is positive, then an NMDA antibody IgG titer is reported

CDC-recommended screening test for syphilis

May use to confirm reactive treponemal test (eg, enzyme immunoassay [EIA], chemiluminescence immunoassay [CIA]) if using so-called reverse algorithm testing

Preferred test for monitoring treatment response in established syphilis

Rapid Plasma Reagin (RPR) with Reflex to Titer 0050471

Method: Semi-Quantitative Charcoal Agglutination

Reflex pattern: if RPR is reactive, then a titer will be added

Confirm toxoplasmosis infection in immunocompromised hosts as well as fetuses and newborns

May be used to confirm equivocal antibody testing

Toxoplasma gondii by PCR 0055591

Method: Qualitative Polymerase Chain Reaction

Aid in the diagnosis of nonacute (chronic phase) Chagas disease (T. cruzi)

Trypanosoma cruzi Antibody, IgG 0051076

Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Generally not recommended for the diagnosis of acute disease/encephalitis

May aid in diagnosing VZV vasculopathy

Varicella-Zoster Virus Antibody, IgG, CSF 0054444

Method: Semi-Quantitative Chemiluminescent Immunoassay

Detect VZV

Negative or inadequate direct fluorescent antibody (DFA) results are confirmed with culture

DFA sensitivity is highest when performed on scraping from the base of lesions; culture sensitivity is highest when specimens are collected soon after onset of symptoms

Molecular testing is generally preferred; refer to VZV by PCR

Varicella-Zoster Virus DFA with Reflex to Varicella-Zoster Virus Culture 0060282

Method: Direct Fluorescent Antibody Stain/Cell Culture

Reflex pattern: If DFA is negative or inadequate, then a VZV culture will be added

Detect VZV in blood, CSF, ocular fluid, tissue, or vesicle fluid

Varicella-Zoster Virus by PCR 0060042

Method: Qualitative Polymerase Chain Reaction

Preferred test for diagnosing West Nile encephalitis

West Nile Virus Antibody, IgM by ELISA, CSF 0050239

Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Detect presence of IgG and IgM antibodies in individuals with a clinical suspicion of West Nile virus

West Nile Virus Antibodies, IgG and IgM by ELISA, Serum 0050226

Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Medical Experts

Fisher, Mark A., PhD, D(ABMM), Medical Director, Bacteriology, and Special Microbiology, Antimicrobial Susceptibility Testing, at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Hillyard, David R., MD, Medical Director, Molecular Infectious Diseases at ARUP Laboratories; Professor of Pathology, University of Utah

Klonoski, Joshua M., MD, PhD, Assistant Medical Director of Informatics and Content Editor at ARUP Laboratories; Resident Physician, Department of Pathology, University of Utah

Palmer, Cheryl Ann, MC, Medical Director at ARUP Laboratories; Professor of Anatomic Pathology, University of Utah

References

Guidelines

Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, Hartman BJ, Kaplan SL, Scheld M, Whitley RJ, Infectious Diseases Society of America. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008; 47(3): 303-27. PubMed
Steiner I, Budka H, Chaudhuri A, Koskiniemi M, Sainio K, Salonen O, Kennedy PG. Viral meningoencephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol. 2010; 17(8): 999-e57. PubMed
Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, Stahl J, Mailles A, Drebot M, Rupprecht CE, Yoder J, Cope JR, Wilson MR, Whitley RJ, Sullivan J, Granerod J, Jones C, Eastwood K, Ward KN, Durrheim DN, Solbrig MV, Guo-Dong L, Glaser CA, International Encephalitis Consortium. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013; 57(8): 1114-28. PubMed
Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Aug 2019]
Britton PN, Eastwood K, Paterson B, Durrheim DN, Dale RC, Cheng AC, Kenedi C, Brew BJ, Burrow J, Nagree Y, Leman P, Smith DW, Read K, Booy R, Jones CA, Australasian Society of Infectious Diseases (ASID), Australasian College of Emergency Medicine (ACEM), Australian and New Zealand Association of Neurologists (ANZAN), Public Health Association of Australia (PHAA). Consensus guidelines for the investigation and management of encephalitis in adults and children in Australia and New Zealand. Intern Med J. 2015; 45(5): 563-76. PubMed

General References

Bennett J, Dolin R, Blaser M. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8th ed. Philadelphia: Elsevier Churchill Livingston, 2014.

Bloch KC, Glaser CA. Encephalitis Surveillance through the Emerging Infections Program, 1997-2010. Emerg Infect Dis. 2015; 21(9): 1562-7. PubMed

Bradshaw MJ, Venkatesan A. Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management. Neurotherapeutics. 2016; 13(3): 493-508. PubMed

George BP, Schneider EB, Venkatesan A. Encephalitis hospitalization rates and inpatient mortality in the United States, 2000-2010. PLoS One. 2014; 9(9): e104169. PubMed

Glaser CA, Gilliam S, Schnurr D, Forghani B, Honarmand S, Khetsuriani N, Fischer M, Cossen CK, Anderson LJ, California Encephalitis Project, 1998-2000. In search of encephalitis etiologies: diagnostic challenges in the California Encephalitis Project, 1998-2000. Clin Infect Dis. 2003; 36(6): 731-42. PubMed

Hunt G. Meningitis and encephalitis in adolescents. Adolesc Med State Art Rev. 2010; 21(2): 287-317, ix-x. PubMed

Lindquist L, Vapalahti O. Tick-borne encephalitis. Lancet. 2008; 371(9627): 1861-71. PubMed

Long SS. Encephalitis diagnosis and management in the real world. Adv Exp Med Biol. 2011; 697: 153-73. PubMed

Love S, Perry A, Ironside J, Budka H. Greenfield’s Neuropathology, Ninth Edition. Boca Raton: CRC Press. Taylor and Francis Group, 2015.

Perry A, Brat DJ. Practical Surgical Neuropathology A Diagnostic Approach, Second. Philadelphia: Elsevier, 2018.

Venkatesan A, Geocadin RG. Diagnosis and management of acute encephalitis: A practical approach. Neurol Clin Pract. 2014; 4(3): 206-215. PubMed

Vora NM, Holman RC, Mehal JM, Steiner CA, Blanton J, Sejvar J. Burden of encephalitis-associated hospitalizations in the United States, 1998-2010. Neurology. 2014; 82(5): 443-51. PubMed

Resources from the ARUP Institute for Clinical and Experimental Pathology®

Bagdure SR, Fisher MA, Ryan ME, Khasawneh FA. Rhodococcus erythropolis encephalitis in patient receiving rituximab. Emerg Infect Dis. 2012; 18(8): 1377-9. PubMed

Suh-Lailam BB, Haven TR, Copple SS, Knapp D, Jaskowski TD, Tebo AE. Anti-NMDA-receptor antibody encephalitis: performance evaluation and laboratory experience with the anti-NMDA-receptor IgG assay. Clin Chim Acta. 2013; 421: 1-6. PubMed

Content Review:

April 2018

Last Update: November 2019

Infectious Encephalitis

Diagnosis

Indications for Testing

Criteria for Diagnosis

Laboratory Testing

Histology

Imaging Studies

Other Tests

Differential Diagnosis (Noninfectious)

Background

Epidemiology

Organisms

Clinical Presentation

ARUP Lab Tests

Medical Experts

References

Guidelines

General References

Resources from the ARUP Institute for Clinical and Experimental Pathology®

ARUP Laboratories

ARUP Websites

ARUP Consult


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Infectious Encephalitis

Diagnosis

Indications for Testing

Criteria for Diagnosis

Laboratory Testing

Histology

​Imaging Studies

Other Tests

Differential Diagnosis (Noninfectious)

Background

Epidemiology

Organisms

Clinical Presentation

ARUP Lab Tests

Medical Experts

References

Guidelines

General References

Resources from the ARUP Institute for Clinical and Experimental Pathology®

ARUP Laboratories

ARUP Websites

ARUP Consult

Imaging Studies