[Postgrad Med J 2022;0:1–10, Clin Microbiol Infect 2017;23:607-13]

- Inflammation of the brain parenchyma, typically caused by either an infectious agent or an autoimmune process which may be postinfectious, paraneoplastic or idiopathic.

- Autoimmune encephalitis:

  • leading cause of encephalitis for patients less than 30 years old - always consider autoimmune/inflammatory encephalitis especially if atypical presentation
  • screening for underlying malignancies is recommended
  • consult Neurology for specific CSF investigations

Jump to Therapy


Epidemiologic clues are important in directing investigation of meningoencephalitis and include:

  • season of year
  • geographic locale
  • local prevalence of potential etiological agents
  • travel history
  • recreational activities
  • occupational exposure
  • insect contact
  • animal contact
  • vaccination history
  • immune status of patient
  • transfusion history
  • sexual history
  • TB exposure/risk

Initial Investigations


(NB: Collect 10-20mL of extra CSF for additional studies): 

- Cell count (predominantly lymphocytic pleocytosis in viral encephalitis), glucose (CSF:blood glucose ratio is typically normal in viral encephalitis), protein (protein may be moderately elevated or normal in viral encephalitis)

- Gram stain and culture (Listeria monocytogenes, N. meningitidis)

- PCR:




- Blood culture

- HIV serology

- Syphilis serology (Treponema pallidum)

- Monospot

- Microscopy and rapid diagnostic test for malaria if travel history to endemic area


Nasopharyngeal washing/swab:

- Respiratory pathogen molecular panel  (influenza, adenovirus, human metapneumovirus, enterovirus/rhinovirus, bocavirus, COVID)


- GI PCR panel (Enterovirus) (if available)


Chest X-ray

EEG and MRI (HSV encephalitis typically causes bilateral but asymmetrical inflammation of the temporal and frontal lobes)

Tuberculin skin test


Secondary Investigations


- Arbovirus serology: West Nile virus and California serogroup and Cache Valley virus serology if mosquito exposure mid-April to November. Send convalescent serology 1-2 weeks later.

- Lyme serology (Borrelia burgdorferi) - if positive consult microbiologist for Lyme PCR on CSF

- Epstein–Barr virus (EBV) VCA IgM

- Cytomegalovirus (CMV) IgG/IgM

- Herpes simplex (HSV) IgG/IgM

- Human Herpes virus 6 (HHV6) and Human Herpes virus 7 (HHV7) IgM



- Pan herpes PCR – HSV 1 & 2, HHV6, HHV7, VZV, CMV, EBV

- Histoplasma antigen



- PCR for West Nile virus (depending on season/local prevalence)

- Cryptococal antigen

- Fungal cultures - Cryptococcus, Coccidioides spp, Histoplasma spp

- Mycobacterial cultures/PCR (M. tuberculosis)



- Coccidioides antigen if compatible travel history/exposure

- Histoplasma antigen if compatible travel history/exposure


Special considerations if initial/secondary investigations negative or deterioration on acyclovir

NB: Initial Herpes PCR may be negative early in course of illness (1-3 days). Repeat CSF for Herpes PCR at 2-7 days before discontinuing acyclovir.


Rare Etiologies:


- Arboviruses (arthropod-borne) - travel history, insect exposure

  • Flaviviruses: Japanese encephalitis, St. Louis encephalitis, West Nile virus, Kunjin virus, Usutu virus, Murray Valley encephalitis, Dengue, Zika virus, Tick borne viruses, Powassan encephalitis
  • Bunyaviruses: California encephalitis virus, La Crosse encephalitis virus, Jamestown Canyon virus, Snowshoe hare virus, Toscana virus, Naples virus, Sicilian virus, Hantavirus
  • Togaviruses: Eastern/Western/Venezuelan equine encephalitis virus, Chikungunya virus

- Rabies virus - animal/occupational exposure

- Herpes B - monkey exposure

- Parvovirus B19 - children/rash, anemia

- JC viruses – immunocompromised

- LCM virus - immunocompromised/rodent exposure

- Measles, mumps, rubella - post infectious/post vaccination (acute disseminated encephalomyelitis)

- Adenoviruses - rare cause of encephalitis in immunocompromised

- Enteroviruses - account for only a small percentage of viral encephalitis cases, especially in children.

- Lassa fever-Arenavirus-West Africa

- Variegated Squirrel bornavirus- after contact with exotic squirrels

- Ebola – central/west Africa



- Bartonella spp: B. henselae - cat exposure, B. bacilliformis - S. America travel

- Tropheryma spp (Whipple's disease)

- Brucella - ingestion of unpasteurized milk/milk products or direct exposure to infected animals

- Leptospira - exposure to contaminated water or food or direct exposure to infected animals


- Coxiella burnetii (Q fever) - contact with sheep, goats, unpasteurized products

- Rickettsia rickettsi (Rocky Mountain Spotted Fever) - travel to endemic areas of Americas

- Ehrlichia chaffeensis - USA travel/coastal areas

- Anaplasma phagocytophilum - travel to endemic area

- Orientia tsutsugamushi - travel to India



- Acanthamoeba spp – immunocompromised, chronic alcoholism

- Naegleria fowleri - swimming in lakes/brackish waters

- Toxoplasma gondii - reactivation in immunocompromised host/intrauterine infection

- Trypanosoma spp - travel to endemic area

- Toxocara - exposure to contaminated soil from dog/cat feces containing infectious eggs



- Taenia solium - immigrants/travel to endemic areas (Mexico, Central/South America)

- Gnathostoma spp - immigrants/travel to southeast Asia; eosinophilia (blood/CSF)

- Baylisascaris procyonis - raccoon exposure (esp feces); eosinophilia (blood/CSF)

- Strongyloides stercoralis - hyperinfection syndrome in immunocompromised host

- Angiostrongyliasis cantonensis – exposure to/ingestion of snails, shrimp; eosinopilia (CSF)


Transmissible spongiform encephalopathy:

- sporadic/variant Creutzfeldt-Jakob disease


Infectious Diseases consult recommended.

Usual Pathogens

Herpes simplex virus 1
Other causes - see Introduction above


Empiric Therapy Dose Duration
Acyclovir 10mg/kg IV q8h 14-21 days for HSV
10-14 days for VZV

Antibacterial (if bacterial meningitis not ruled out)

Empiric Therapy Dose Duration
Ceftriaxone 2g IV q12h  
Vancomycin 15mg/kg IV q8-12h  
Ampicillin 2g IV q4h  
Doxycycline 200mg IV/PO once then 100mg IV/PO bid