Encephalitis
[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
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:
- Herpes simplex virus (HSV) 1 and 2
- meningoencephalitis molecular panel (if available)
- Varicella zoster virus (VZV)
- Enterovirus
- Meningococcus (if clinical suspicion)
- VDRL
Blood:
- 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)
Stool:
- 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
Blood:
- 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
CSF/Blood:
- Pan herpes PCR – HSV 1 & 2, HHV6, HHV7, VZV, CMV, EBV
- Histoplasma antigen
CSF:
- PCR for West Nile virus (depending on season/local prevalence)
- Cryptococal antigen
- Fungal cultures - Cryptococcus, Coccidioides spp, Histoplasma spp
- Mycobacterial cultures/PCR (M. tuberculosis)
Urine:
- 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:
Viral
- 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, Oropouche virus
- 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
Bacterial
- 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
Rickettsial
- 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
Protozoal
- 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
Helminths
- 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.
Herpes simplex virus 1
Enteroviruses
Other causes - see Introduction above
HSV
| 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 |