Table 1: Possible etiologic agents of encephalitis based on epidemiology and risk factors.
Epidemiology or risk factor
Possible infectious agent(s)
Infants and children
West Nile virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, Cryptococcus neoformans (bird droppings), rabies virus.
Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Hendra virus
Old World primates
Eastern equine encephalitis virus (South America), Venezuelan equine encephalitis virus, tick-borne encephalitis virus, Powassan virus (woodchucks), La Crosse virus (chipmunks and squirrels), Bartonella quintana
Sheep and goats
Japanese encephalitis virus, Nipah virus
Varicella zoster virus, cytomegalovirus, human herpesvirus 6, West Nile virus, HIV, JC virus, L. monocytogenes, Mycobacterium tuberculosis, C. neoformans, Coccidioides species, Histoplasma capsulatum, T. gondii
Raw or partially cooked meat
Raw meat, fish, or reptiles
Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, West Nile virus, La Crosse virus, Plasmodium falciparum
Exposure to animals
Exposure to horses
Exposure to Old World primates
Physicians and health care workers
Herpes simplex virus (neonatal), varicella zoster virus, Venezuelan equine encephalitis virus (rare), poliovirus, nonpolio enteroviruses, measles virus, Nipah virus, mumps virus, rubella virus, Epstein-Barr virus, human herpesvirus 6, B virus, West Nile virus (transfusion, transplantation, breast feeding), HIV, rabies virus (transplantation), influenza virus, M. pneumoniae, M. tuberculosis, T. pallidum
Acute disseminated encephalomyelitis
All agents transmitted by mosquitoes and ticks (see above)
HIV, T. pallidum
Enteroviruses, Naegleria fowleri
Late summer/early fall
All agents transmitted by mosquitoes and ticks (see above), enteroviruses
Transfusion and transplantation
Cytomegalovirus, Epstein-Barr virus, West Nile virus, HIV, tick-borne encephalitis virus, rabies virus, iatrogenic CJD, T. pallidum, A. phagocytophilum, R. rickettsii, C. neoformans, Coccidioides species, H. capsulatum, T. gondii
Murray Valley encephalitis virus, Japanese encephalitis virus, Hendra virus
West Nile virus, tick-borne encephalitis virus, A. phagocytophilum, B. burgdorferi
West Nile virus, P. falciparum
Tick-borne encephalitis virus
Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, B. bacilliformis (Andes mountains), P. falciparum, T. solium
Southeast Asia, China, Pacific Rim
Japanese encephalitis virus, tick-borne encephalitis virus, Nipah virus, P. falciparum, Gnanthostoma species, T. solium
Table 2: Possible etiologic agents of encephalitis based on clinical findings.
Possible infectious agent
HIV, Epstein-Barr virus, cytomegalovirus, measles virus, rubella virus, West Nile virus, Treponema pallidum, Bartonella henselae and other Bartonella species, Mycobacterium tuberculosis, Toxoplasma gondii, Trypanosoma brucei gambiense
Varicella zoster virus, B virus, human herpesvirus 6, West Nile virus, rubella virus, some enteroviruses, HIV, Rickettsia rickettsii, Mycoplasma pneumoniae, Borrelia burgdorferi, T. pallidum, Ehrlichia chaffeensis, Anaplasma phagocytophilum
Respiratory tract findings
St. Louis encephalitis virus (early)
Cranial nerve abnormalities
T. whipplei (oculomasticatory)
Parkinsonism (bradykinesia, masked facies, cogwheel rigidity, postural instability)
Poliomyelitis-like flaccid paralysis
Diagnostic Alogrithm for Initial Evaluation in Adults:
Diagnostic Algorithm for Children:
Always indicated in suspected encephalitis cases until HSV comfortably ruled-out by PCR study or good alternative diagnostic explanation.
Meropenem and imipenem have been shown to be bactericidal for listeria and may be considered as alternatives when ampicillin, penicillin, and trimethoprim/sulfamethoxazole are not tolerated. These drugs are virtually untested clinically; however, meropenem appears to have less potential to lower the seizure threshold and is thus the favored carbapenem for treating CNS infections.
Use should be considered for any pts with potential risk for tick-borne infections such as RMSF, other rickettsial infections including ehrlichia.
Human immunodeficiency virus
St Louis encephalitis virus
Albendazole + diethylcarbamazine
Albendazole + corticosteroids
Comment: Helpful guidance that sets priorities including definition of encephalitis as well as suggested diagnostic algorithm.
Comment: First comprehensive guideline ever published for encephalitis. Document has extensive information that helps the clinician regarding signs, symptoms, epidemiological risks and diagnostic approaches.
Comment: Includes strategies in critically ill patients that may require ICU monitoring.
Comment: More than a primer on an often competing diagnosis under consideration.
Comment: Hepatitis E has been increasingly described as causing a range of neurological problems including Guillain−Barré syndrome (GBS), neuralgic amyotrophy, and encephalitis and/or myelitis. --albeit uncommonly.
Comment: Extra valacyclovir beyond standard IV therapy for 90d appeared to offer no benefit in this RCT of 87 pts.
Comment: Powassan/Deer Tick virus is probably under-recognized. Testing usually needs to be coordinated on CSF or serum through local heatlh department.
Comment: Search for relevant literature yielded 67 studies with findings of muscle weakness, memory loss, and difficulties with activities of daily living among the most common physical, cognitive, and functional sequelae, respectively/ Increased risks of significant sequelae were seen in older men with underlying illnesses such as cardiovascular disease or cancer.
Comment: In the California Encephalitis Project study, anti-NMDAR encephalitis proved to be the cause of encephalitis that was 4x more frequent then other causes often diagnosed by infectious diseases physician such as herpes simplex virus, West Nile virus were varicella zoster virus.
Comment: Phase I and IIa studies have interesting PK/PD information regarding ribavirin; however, this available data does not suggest benefit and treatment of lacrosse encephalitis.
Comment: Interesting study that suggests high-dose valacyclovir (1000 mg three times daily) achieves suitable CSF levels and may be an option in resource limited countries where parenteral acyclovir here may not be feasible.
Comment: Authors examine literature and suggest that many cases of encephalitis without defined etiology may have an explanation (infectious or auto-immune) and therefore continued efforts are needed to understand causes.
Comment: NMDA (N-methyl-D-aspartate) receptor antibody encephalitis is an autoimmune disorder that can present acutely and be confused with viral meningitis. CSF pleocytosis and elevated protein levels exist for both the autoimmune and the infectious categories.
This entity primarily afflicts children, teens, or young adults often with very prominent psychiatric features. Some may have autonomic dysfunction leading to concern of rabies.
Comment: Comprehensive review of a problem of tick-borne encephalitis that is mostly due to flavivirus infections seen in Western Europe extending through Eurasia to Japan. As no effective treatment is known, prevention through immunization is the best strategy.
Comment: Longitudinal cohort of 156 pts. Most recovered both mental and physical function by 1 year after infection onset. Presence of comorbid conditions was associated with a slower recovery. Depression, fatigue and mood issues did not seem to persist longer in the group with more severe, neuroinvasive disease.
Comment: Subset of WNV encephalitis patients have unresolved neurological sequelae.
Comment: Trial looking at a next generation inactivated JEV vaccine that avoids the issues known to the currently licensed, mouse-brain-derived vaccine. The new vaccine provided 98% seroconversion (compared to current 95%) and had a good side effect profile.
Comment: Comprehensive review on the subject including latest diagnostics.
Comment: Comprehensive update on the newly seen North American infection. Includes information on encephalitic, meningoencephalitic and ascending paralysis style presentations. Diagnostics discussed.
Comment: Study investigating the spectrum of illness associated with herpes simplex infection, as established by PCR assay. Atypical cases were found, including brainstem encephalitis, chronic encephalitis, and milder forms of encephalitis that were poorly appreciated in the era in which brain biopsy was necessary for diagnosis.
Comment: Recent review of pathogenesis and diagnostic and therapeutic strategies. Normal function is established in only 38% of patients treated with acyclovir. Glasgow coma score <6, age >30, and encephalitis >4 days duration are poor prognostic factors. 5-10% of patients relapse after a 10-14 day course of therapy.
Comment: Study establishing PCR detection of HSV DNA as the standard for diagnosis of herpes simplex encephalitis.
Comment: While the outcome of VZV meningoencephalitis in immunocompetent patients is generally favorable, reports indicate patients with HIV infection may have worse outcomes. These 4 patients appeared to benefit from IV acyclovir or ganciclovir given for 10-14 days.
Comment: Review of the literature available for this rare manifestation of listerial infection. Early treatment with ampicillin or penicillin was associated with > 70% survival. Limited data available for alternative therapies, although trimethoprim/sulfamethoxazole was used successfully.
Comment: Study of 432 patients who underwent brain biopsy for presumed HSV encephalitis. 45% had HSV, but 9% (16% of those without HSV) had other treatable etiologies. In cases in which the diagnosis cannot be made non-invasively, the yield for brain biopsy would appear to outweigh the risks, particularly in immunocompromised patients.
Comment: Basis of the recommendations for treatment courses of 14-21 days with IV acyclovir.
Comment: One of two controlled trials showing a beneficial effect of acyclovir over vidarabine on mortality.
Comment: Presentation and discussion of acute encephalopathy associated with acute HIV infection (seroconversion). This form of encephalopathy may be severe but typically has onset and resolution within one week. It is surely under recognized. The diagnosis may require viral load testing, as serological testing may be negative or indeterminate.
Comment: Update on the outbreak of arboviral encephalitis that affected 56 patients, with 7 deaths. This was the North American debut for this flavivirus, which is transmitted within the avian population.
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