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"The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America"

Published: Clinical Infectious Diseases ; 2008 ; 47 : 303 -327


Guidelines for the diagnosis and treatment of patients with encephalitis were prepared by an Expert Panel of the Infectious Diseases Society of America. The guidelines are intended for use by health care providers who care for patients with encephalitis. The guideline includes data on the epidemiology, clinical features, diagnosis, and treatment of many viral, bacterial, fungal, protozoal, and helminthic etiologies of encephalitis and provides information on when specific etiologic agents should be considered in individual patients with encephalitis. 

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*Every 12 to 18 months following publication, IDSA reviews its guidelines to determine whether an update is required. This guideline was last reviewed and deemed current as of 07/2011.



  1. Epidemiologic clues and assessment of risk factors to identify potential etiologic agents should be sought in all patients with encephalitis (table 2) (A-III).
  2. Clinical clues (general and specific neurologic findings) may be helpful in suggesting certain causative agents in patients with encephalitis (table 3) (B-III).
  3. In patients with encephalitis and a history of recent infectious illness or vaccination, the diagnosis of ADEM should be considered (B-III).


  1. Specific diagnostic studies should be performed for the majority of patients who present with encephalitis (table 4) (AIII).
  2. Additional diagnostic studies should be performed for patients with encephalitis on the basis of specific epidemiologic and clinical clues (tables 2, 3, and 5) (A-III).

Diagnostic Studies outside the CNS

  1. Cultures of body fluid specimens (e.g., from blood, stool, nasopharynx, or sputum), if clinical and epidemiologic clues are suggestive, should be performed in an attempt to identify various viral, bacterial, and fungal etiologies of encephalitis (table 5) (B-III); positive results do not necessarily indicate that the isolated microorganism is the etiology of encephalitis and must be interpreted in the context of the appropriate epidemiologic findings, clinical findings, and other diagnostic study results.
  2. Biopsy of specific tissues for culture, antigen detection, nucleic acid amplification tests (such as PCR), and histopathologic examination should be performed in an attempt to establish an etiologic diagnosis of encephalitis (table 5) (A-III).
  3. Certain causes of encephalitis may be diagnosed by detection of IgM antibodies in serum (table 5) (A-III).
  4. Although acute- and convalescent-phase serum samples are generally not useful in establishing the etiology during the acute presentation in a patient with encephalitis, they may be useful for the retrospective diagnosis of an infectious agent (table 5) (B-III).
  5. Nucleic acid amplification tests (such as PCR) of body fluids outside of the CNS may be helpful in establishing the etiology in some patients with encephalitis (table 5) (B-III).

Neurodiagnostic Studies

  1. MRI is the most sensitive neuroimaging test to evaluate patients with encephalitis (A-I).
  2. CT, with and without contrast enhancement, should be used to evaluate patients with encephalitis if MRI is unavailable, impractical, or cannot be performed (B-III).
  3. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scanning is not routinely recommended for patients with encephalitis.
  4. Electroencephalography (EEG) is rarely helpful in establishing an etiology in patients with encephalitis, but it has a role in identifying patients with nonconvulsive seizure activity who are confused, obtunded, or comatose and should be performed in all patients with encephalitis (A-III).
  5. CSF analysis is essential (unless contraindicated) in all patients with encephalitis (A-III).

Diagnostic Studies in the CNS

  1. For certain viral agents, the presence of virus-specific IgM in CSF specimens may be indicative of CNS disease caused by that pathogen (table 5) (A-III).
  2. Nucleic acid amplification tests (such as PCR) should be performed on CSF specimens to identify certain etiologic agents in patients with encephalitis (table 5) (A-III). Although a positive test result is helpful in diagnosing infection caused by a specific pathogen, a negative result cannot be used as definitive evidence against the diagnosis.
  3. Herpes simplex PCR should be performed on all CSF specimens in patients with encephalitis (A-III). In patients with encephalitis who have a negative herpes simplex PCR result, consideration should be given to repeating the test 3–7 days later in those with a compatible clinical syndrome or temporal lobe localization on neuroimaging (B-III).
  4. Viral cultures of CSF specimens are of limited value in patients with encephalitis and are not routinely recommended.
  5. Brain biopsy should not be routinely used in patients with encephalitis but should be considered in patients with encephalitis of unknown etiology whose condition deteriorates despite treatment with acyclovir (B-III).


Empirical Therapy

  1. Acyclovir should be initiated in all patients with suspected encephalitis, pending results of diagnostic studies (AIII).
  2. Other empirical antimicrobial agents should be initiated on the basis of specific epidemiologic or clinical factors (tables 2 and 3), including appropriate therapy for presumed bacterial meningitis, if clinically indicated (A-III).
  3. In patients with clinical clues suggestive of rickettsial or ehrlichial infection during the appropriate season, doxycycline should be added to empirical treatment regimens (A-III).

Specific Therapy


  1. Herpes simplex virus: acyclovir is recommended (AI).
  2. Varicella-zoster virus: acyclovir is recommended (BIII); ganciclovir can be considered an alternative (C-III); adjunctive corticosteroids can be considered (C-III).
  3. Cytomegalovirus: the combination of ganciclovir plus foscarnet is recommended (B-III); cidofovir is not recommended, because its ability to penetrate the blood-brain barrier has been poorly studied.
  4. Epstein-Barr virus: acyclovir is not recommended; the use of corticosteroids may be beneficial (C-III), but the potential risks must be weighed against the benefits.
  5. Human herpesvirus 6: ganciclovir or foscarnet should be used in immunocompromised patients (B-III); use of these agents in immunocompetent patients can be considered (CIII), but there are not good data on their effectiveness.
  6. B virus: valacyclovir is recommended (B-III); alternative agents are ganciclovir (B-III) and acyclovir (C-III).
  7. Influenza virus: oseltamivir can be considered (C-III).
  8. Measles virus: ribavirin can be considered (C-III); intrathecal ribavirin can be considered in patients with subacute sclerosing panencephalitis (C-III).
  9. Nipah virus: ribavirin can be considered (C-III).
  10. West Nile virus: ribavirin is not recommended.
  11. Japanese encephalitis virus: IFN-a is not recommended.
  12. St. Louis encephalitis virus: IFN-2a can be considered (C-III).
  13. HIV: HAART is recommended (A-II).
  14. JC virus: reversal of immunosuppression (A-III)—or HAART in HIV-infected patients (A-II)—is recommended.


  1. Bartonella bacilliformis: chloramphenicol, ciprofloxacin, doxycycline, ampicillin, or trimethoprim-sulfamethoxazole is recommended (B-III).
  2. Bartonella henselae: doxycycline or azithromycin, with or without rifampin, can be considered (C-III).
  3. Listeria monocytogenes: ampicillin plus gentamicin is recommended (A-III); trimethoprim-sulfamethoxazole is an alternative in the penicillin-allergic patient (A-III).
  4. Mycoplasma pneumoniae: antimicrobial therapy (azithromycin, doxycycline, or a fluoroquinolone) can be considered (C-III).
  5. Tropheryma whipplei: ceftriaxone, followed by either trimethoprim-sulfamethoxazole or cefixime, is recommended (B-III). Mycobacteria
  6. Mycobacterium tuberculosis: 4-drug antituberculous therapy should be initiated (A-III); adjunctive dexamethasone should be added in patients with meningitis (B-I). Rickettsioses and ehrlichioses
  7. Anaplasma phagocytophilum: doxycycline is recommended (A-III).
  8. Ehrlichia chaffeensis: doxycycline is recommended (AII).
  9. Rickettsia rickettsii: doxycycline is recommended (AII); chloramphenicol can be considered an alternative in selected clinical scenarios, such as pregnancy (C-III).
  10. Coxiella burnetii: doxycycline plus a fluoroquinolone plus rifampin is recommended (B-III). Spirochetes
  11. Borrelia burgdorferi: ceftriaxone, cefotaxime, or penicillin G is recommended (B-II).
  12. Treponema pallidum: penicillin G is recommended (AII); ceftriaxone is an alternative (B-III).


  1. Coccidioides species: fluconazole is recommended (AII); alternatives are itraconazole (B-II), voriconazole (B-III), and amphotericin B (intravenous and intrathecal) (C-III).
  2. Cryptococcus neoformans: initial treatment with amphotericin B deoxycholate plus flucytosine (A-I) or a lipid formulation of amphotericin B plus flucytosine (A-II) is recommended.
  3. Histoplasma capsulatum: liposomal amphotericin B followed by itraconazole is recommended (B-III).


  1. Acanthamoeba: trimethoprim-sulfamethoxazole plus rifampin plus ketoconazole (C-III) or fluconazole plus sulfadiazine plus pyrimethamine (C-III) can be considered.
  2. Balamuthia mandrillaris: pentamidine, combined with a macrolide (azithromycin or clarithromycin), fluconazole, sulfadiazine, flucytosine, and a phenothiazine can be considered (C-III).
  3. Naegleria fowleri: amphotericin B (intravenous and intrathecal) and rifampin, combined with other agents, can be considered (C-III).
  4. Plasmodium falciparum: quinine, quinidine, or artemether is recommended (A-III); atovaquone-proguanil is an alternative (B-III); exchange transfusion is recommended for patients with 110% parasitemia or cerebral malaria (B-III); corticosteroids are not recommended.
  5. Toxoplasma gondii: pyrimethamine plus either sulfadiazine or clindamycin is recommended (A-I); trimethoprimsulfamethoxazole alone (B-I) and pyrimethamine plus either atovaquone, clarithromycin, azithromycin, or dapsone (B-III) are alternatives.
  6. Trypanosoma brucei gambiense: eflornithine is recommended (A-II); melarsoprol is an alternative (A-II).
  7. Trypanosoma brucei rhodesiense: melarsoprol is recommended (A-II). Helminths
  8. Baylisascaris procyonis: albendazole plus diethycarbamazine can be considered (C-III); adjunctive corticosteroids should also be considered (B-III).
  9. Gnathostoma species: albendazole (B-III) or ivermectin (B-III) is recommended.
  10. Taenia solium: need for treatment should be individualized; albendazole and corticosteroids are recommended (BIII); praziquantel can be considered as an alternative (C-II). Postinfectious/postvaccination status
  11. Acute disseminated encephalomyelitis: high-dose corticosteroids are recommended (B-III); alternatives include plasma exchange (B-III) and intravenous immunoglobulin (CIII).

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