Encephalitis

PATHOGENS

CLINICAL

  • Fever, cognitive deficits, focal neurologic signs (often rapidly progressive), and/or seizures preceded by nonspecific/flu-like prodrome.
  • Review travel, sexual contact, tick/insect hx.
    • Obtain hx looking for epidemiological risks including geography, exposure to vectors, time of year, travel hx, animal contact, recent vaccines, occupational exposure (especially lab workers).
  • PE: meningeal signs (meningoencephalitis), abnormal mental status with ataxia, hemiparesis, aphasia, cranial nerve involvement and psychosis possible.
  • Ddx: among most common--arboviruses (summer-fall), HSV (most common sporadic cause), enterovirus (summer-fall), toxic/metabolic explanations, CNS vasculitis, paraneoplastic syndromes, post-infectious or post-immunization encephalitis/encephalomyelitis (e.g., ADEM).


Table 1: Possible etiologic agents of encephalitis based on epidemiology and risk factors[2].

Epidemiology or risk factor

Possible infectious agent(s)

Agammaglobulinemia

Enteroviruses, Mycoplasma pneumoniae

Age

Neonates

Herpes simplex virus type 2, cytomegalovirus, rubella virus, Listeria monocytogenes, Treponema pallidum, Toxoplasma gondii

Infants and children

Eastern equine encephalitis virus, Japanese encephalitis virus, Murray Valley encephalitis virus (rapid in infants), influenza virus, La Crosse virus

Elderly persons

Eastern equine encephalitis virus, St. Louis encephalitis virus, West Nile virus, sporadic CJD, L. monocytogenes

Animal contact

Bats

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.

Cats

Rabies virus, Coxiella burnetii, Bartonella henselae, T. gondii

Dogs

Rabies virus

Horses

Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Hendra virus

Old World primates

B virus

Rodents

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

C. burnetii

Skunks

Rabies virus

Swine

Japanese encephalitis virus, Nipah virus

White-tailed deer seen, potential for tick exposure

Borrelia burgdorferi(rare)

Borrelia miyamotoi(mostly described in the immunosuppressed)

Immunocompromised persons

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

Ingestion items

Raw or partially cooked meat

T. gondii

Raw meat, fish, or reptiles

Gnathostomiasis

Unpasteurized milk

Tick-borne encephalitis virus, L. monocytogenes, C. burnetii

Insect contact

Mosquitoes

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

Sandflies

Bartonella bacilliformis

Ticks

Tick-borne encephalitis virus, Powassan virus, Rickettsia rickettsii, Ehrlichia chaffeensis, Anaplasma phagocytophilum, C. burnetii (rare), B. burgdorferi

Tsetse flies

Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense

Occupation

Exposure to animals

Rabies virus, C. burnetii, Bartonella species

Exposure to horses

Hendra virus

Exposure to Old World primates

B virus

Physicians and health care workers

Varicella zoster virus, HIV, influenza virus, measles virus, M. tuberculosis

Veterinarians

Rabies virus, Bartonella species, C. burnetii

Person-to-person transmission

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

Recent vaccination

Acute disseminated encephalomyelitis

Recreational activities

Camping/hunting

All agents transmitted by mosquitoes and ticks (see above)

Sexual contact

HIV, T. pallidum

Spelunking

Rabies virus, Histoplasma capsulatum

Swimming

Enteroviruses, Naegleria fowleri

Season

Late summer/early fall

All agents transmitted by mosquitoes and ticks (see above), enteroviruses

Winter

Influenza virus

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, Coccidioidesspecies, H. capsulatum, T. gondii

Travel

Africa

Rabies virus, West Nile virus, P. falciparum, T. brucei gambiense, T. brucei rhodesiense

Australia

Murray Valley encephalitis virus, Japanese encephalitis virus, Hendra virus

Central America

Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, P. falciparum,Taenia solium

Europe

West Nile virus, tick-borne encephalitis virus,A. phagocytophilum, B. burgdorferi

India, Nepal

Bihar encephalitis (unknown cause, in lychee-fruit growing areas)

Rabies virus, Japanese encephalitis virus, P. falciparum

Middle East

West Nile virus,P. falciparum

Russia

Tick-borne encephalitis virus

South America

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, Gnathostomaspecies,T. solium

Unvaccinated status

Varicella zoster virus, Japanese encephalitis virus, poliovirus, measles virus, mumps virus, rubella virus

Table 2: Possible etiologic agents of encephalitis based on clinical findings[2].

Clinical presentation

Possible infectious agent

General findings

Hepatitis

Coxiella burnetii

Lymphadenopathy

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

Parotitis

Mumps virus

Rash

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

Venezuelan equine encephalitis virus, Nipah virus, Hendra virus, influenza virus, adenovirus, M. pneumoniae, C. burnetii, M. tuberculosis, Histoplasma capsulatum

Retinitis

Cytomegalovirus, West Nile virus, B. henselae, T. pallidum

Urinary symptoms

St. Louis encephalitis virus (early)

Neurologic findings

Cerebellar ataxia

Varicella zoster virus (children), Epstein-Barr virus, mumps virus, St. Louis encephalitis virus, Tropheryma whipplei,T. brucei gambiense

Cranial nerve abnormalities

Herpes simplex virus, Epstein-Barr virus, Listeria monocytogenes, M. tuberculosis, T. pallidum, B. burgdorferi,T. whipplei, Cryptococcus neoformans, Coccidioides species, H. capsulatum

Dementia

HIV, human transmissible spongiform encephalopathies (sCJD and vCJD), measles virus (SSPE), T. pallidum, T. whipplei

Myorhythmia

T. whipplei (oculomasticatory)

Parkinsonism (bradykinesia, masked facies, cogwheel rigidity, postural instability)

Japanese encephalitis virus, St. Louis encephalitis virus, West Nile virus, Nipah virus, T. gondii, T. brucei gambiense

Poliomyelitis-like flaccid paralysis

Japanese encephalitis virus, West Nile virus, tick-borne encephalitis virus; enteroviruses (enterovirus-71, coxsackieviruses),poliovirus

Rhombencephalitis

Herpes simplex virus, West Nile virus, enterovirus 71, L. monocytogenes

DIAGNOSIS

  • MRI may be normal in many cases early on. May show temporal lobe changes (in HSV) or more diffuse involvement.
  • EEG abnormal in many cases of HSV encephalitis with characteristic temporal lobe spikes. Should be performed in all pts to rule out non-convulsive seizure activity.
  • Lab: obtain CSF if safe to do so, usually w/ mononuclear cells and increased protein; CSF PCRs, CSF culture (viral cx of limited value), or serology (based on suspected agents: IgM, acute/convalescent IgG or CSF antibodies).
    • HSV PCR should be performed on all pts with encephalitis. If negative, repeat w/i 3-7d in pts with compatible findings if not other diagnosis secured.
    • Note: negative PCR test is not absolute evidence that a certain infection is not extant.
    • Autoimmune N-methyl-D-aspartate receptor encephalitis in one large series was identified as the leading cause of encephalitis (4x >HSV, VZV, WNV)[13].
  • Consider brain biopsy in pts with continued deterioration despite acyclovir.
  • Many cases without known etiology despite extensive testing.

Diagnostic Alogrithm for Initial Evaluation in Adults[1]:

See Diagnostic Alogrithm for Initial Evaluation in Adults Table

Diagnostic Algorithm for Children[1]:

See Diagnostic Algorithm for Children Table

  • If infectious diagnosis not rapidly achieved, consider obtaining anti-NMDAR antibody testing as it is a leading cause of encephalitis[13].

TREATMENT

General recommendations, empiric therapy

  • Important to consider treatable causes and use empiric therapy.
  • Supportive care is all that can be done for most pts.
  • Many cases of encephalitis without an identifiable cause or due to a virus without known therapy.

Viral encephalitis, treatable causes

  • HSV: acyclovir 10mg/kg IV q8h x 14-21d.
    • In neonates: 20mg/kg IV q8h x 21d.
    • If good response not seen, f/u LP and treat until HSV PCR negative.
  • VZV: acyclovir 10-15mg/kg IV q8h x 10-14d. Alternative: ganciclovir.
  • CMV: ganciclovir 5 mg/kg IV q12h x 14-21 days; then 5mg/kg IV every day for maintenance .
    • Some combine ganciclovir w/ foscarnet 90mg/kg IV q12h w/ 90-120mg/kg IV every day for maintenance, especially with HIV CMV CNS infection.
    • Reduce immune suppression, if possible.
    • Consider HAART in HIV pts.
    • Note: cidofovir penetrates into CSF poorly, not recommended.
  • B virus: ganciclovir 5 mg/kg IV twice daily or acyclovir 15 mg/kg IV q8h x > 14d or until all CNS sx resolve, then acyclovir 800 mg PO 5 times daily or valacyclovir 1 g PO three times a day indefinitely. See B virus module for details.
  • HHV-6: case reports suggest ganciclovir or foscarnet may help. Follow CMV recommendations.

Nonviral encephalitis

  • Listeria: ampicillin 2mg IV q4h + gentamicin 5mg/kg/d IV divided q8h x 3-6 weeks.
    • Alternative: TMP/SMX 15mg/kg/d IV divided q6h x 3-6 weeks.
  • Toxoplasmosis:
    • Pyrimethamine 100-200mg orally once (loading dose), then 50-100mg PO every day + sulfadiazine 4-8 g PO every day + folinic acid 10mg PO every day x minimum 6 weeks.
    • Pyrimethamine 100-200mg PO once (loading dose), then 50-100mg PO every day + clindamycin 900mg IV q6h + folinic acid 10mg PO every day x minimum 6 weeks.

Postinfectious/postvaccination-related

  • Autoimmune encephalitis[8]: often a probable rather than a definitive diagnosis.
  • Acute disseminated encephalomyelitis: neurology consultation, high-dose corticosteroids recommended. Plasma exchange or IV IgG could be considered.
  • Anti-NMDAR encephalitis: antibody-mediated process directed against extracellular epitopes of NR1subunit epitope of NMDA receptor.
    • May occur as a paraneoplastic–driven process, especially ovarian teratoma.
    • Approximately 75% rate seen following tumor removal, or if non-tumor related, use of corticosteroids, immunoglobulin, plasmapheresis, rituximab or cyclophosphamide.

Prevention

  • Tick-borne encephalitis virus: flavivirus infection seen in Western Europe through Eurasia.
    • Serology to diagnose. No effective treatment is known.
    • Commercial vaccine available in Europe and is thought to be >95% effective.
  • Japanese encephalitis virus: vaccine available, recommended for people living in rural, rice-growing parts of Asia or who are traveling to such regions with extended stay and for laboratory workers at risk for exposure.

Selected Drug Comments

Drug

Recommendation

Acyclovir

Always indicated in suspected encephalitis cases until HSV comfortably ruled-out by PCR study or good alternative diagnostic explanation.

Meropenem

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.

Doxycycline

Use should be considered for any patients with potential risk for tick-borne infections such as RMSF, other rickettsial infections including Ehrlichia.

FOLLOW UP

  • The relapse rate of HSV encephalitis maybe 5% or more. Negative HSV PCR in CSF portends for better outcome, less relapse--especially in neonates.

OTHER INFORMATION

  • HSV is critical to treat rapidly.
    • Clues: fever, seizure, mental status or personality changes, focal neurological deficits, temporal lobe involvement on MRI. ALWAYS start empiric acyclovir while awaiting test results.
    • CSF showing RBCs and elevated protein (HSV meningitis).
    • No HSV skin lesions seen in the majority.
  • Suspected or proven HSV: use acyclovir IV. If dx studies negative--may need brain biopsy if suspicious.

Pathogen Specific Therapy

Basis for recommendation

  1. Venkatesan A, Tunkel AR, Bloch KC, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013;57(8):1114-28.  [PMID:23861361]

    Comment: Helpful guidance that sets priorities including the definition of encephalitis as well as suggested diagnostic algorithm.

  2. Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008;47(3):303-27.  [PMID:18582201]

    Comment: First comprehensive guideline ever published for encephalitis. The document has extensive information that helps the clinician regarding signs, symptoms, epidemiological risks and diagnostic approaches.

References

  1. Britton PN, Dale RC, Blyth CC, et al. Causes and Clinical Features of Childhood Encephalitis: A Multicenter, Prospective Cohort Study. Clin Infect Dis. 2019.  [PMID:31549170]

    Comment: Study of 287 children in Australia found the following causes of encephalitis in confirmed cases: 57% (95% confidence interval [CI], 52%-63%) had infectious causes, 10% enterovirus, 10% parechovirus, 8% bacterial meningoencephalitis, 6% influenza, 6% herpes simplex virus (HSV), and 6% Mycoplasma pneumoniae; 25% (95% CI, 20%-30%) had immune-mediated encephalitis, 18% acute disseminated encephalomyelitis, and 6% anti-N-methyl-d-aspartate receptor encephalitis; and 17% (95% CI, 13%-21%) had an unknown cause.

  2. Ruzek D, Avšič Županc T, Borde J, et al. Tick-borne encephalitis in Europe and Russia: Review of pathogenesis, clinical features, therapy, and vaccines. Antiviral Res. 2019;164:23-51.  [PMID:30710567]

    Comment: A flavivirus that is transmitted by ticks in Europe, Russia and Asia that in countries where the infection is common strategies include the use of a protective vaccine, specific anti-TBEV immunoglobulin for post-exposure prophylaxis (available only in Russia). Unfortunately, uptake of the vaccine is relatively low.

  3. Dalmau J, Graus F. Antibody-Mediated Encephalitis. N Engl J Med. 2018;378(9):840-851.  [PMID:29490181]

    Comment: Helpful review with NMDAR among the most frequently encountered cause of antibody-mediated encephalitis. Many others are listed along with there associations (see Table 1 in this article).

  4. Backman R, Foy R, Diggle PJ, et al. A pragmatic cluster randomised controlled trial of a tailored intervention to improve the initial management of suspected encephalitis. PLoS One. 2018;13(12):e0202257.  [PMID:30521521]

    Comment: 24 hospitals in the United Kingdom had the implementation of protocols regarding encephalitis occluding lumbar puncture within 12 hours and instituting acyclovir within 6 hours. The interventions had no benefit obvious compared to control; however, both hospitals added 8.5% improvement compared to preintervention suggesting some spillover of educational aspects

  5. Stahl JP, Azouvi P, Bruneel F, et al. Guidelines on the management of infectious encephalitis in adults. Med Mal Infect. 2017;47(3):179-194.  [PMID:28412044]

    Comment: Guidelines from France, that offer fairly specific management recommendations regarding testing and treatment (lots of "ifs, then."

  6. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016.  [PMID:26906964]

    Comment: More than a primer on an often competing diagnosis under consideration.

  7. Dalton HR, Kamar N, van Eijk JJ, et al. Hepatitis E virus and neurological injury. Nat Rev Neurol. 2016;12(2):77-85.  [PMID:26711839]

    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.

  8. Gnann JW, Sköldenberg B, Hart J, et al. Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-term Valacyclovir Therapy. Clin Infect Dis. 2015;61(5):683-91.  [PMID:25956891]

    Comment: Extra valacyclovir beyond standard IV therapy for 90d appeared to offer no benefit in this RCT of 87 pts.

  9. Wormser GP, Pritt B. Update and Commentary on Four Emerging Tick-Borne Infections: Ehrlichia muris-like Agent, Borrelia miyamotoi, Deer Tick Virus, Heartland Virus, and Whether Ticks Play a Role in Transmission of Bartonella henselae. Infect Dis Clin North Am. 2015;29(2):371-81.  [PMID:25999230]

    Comment: Powassan/Deer Tick virus is probably under-recognized. Testing usually needs to be coordinated on CSF or serum through the local health department.

  10. Patel H, Sander B, Nelder MP. Long-term sequelae of West Nile virus-related illness: a systematic review. Lancet Infect Dis. 2015;15(8):951-9.  [PMID:26163373]

    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.

  11. Gable MS, Sheriff H, Dalmau J, et al. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis. 2012;54(7):899-904.  [PMID:22281844]

    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.
    Rating: Important

  12. McJunkin JE, Nahata MC, De Los Reyes EC, et al. Safety and pharmacokinetics of ribavirin for the treatment of la crosse encephalitis. Pediatr Infect Dis J. 2011;30(10):860-5.  [PMID:21544005]

    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.

  13. Pouplin T, Pouplin JN, Van Toi P, et al. Valacyclovir for herpes simplex encephalitis. Antimicrob Agents Chemother. 2011;55(7):3624-6.  [PMID:21576427]

    Comment: An 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.

  14. Granerod J, Tam CC, Crowcroft NS, et al. Challenge of the unknown. A systematic review of acute encephalitis in non-outbreak situations. Neurology. 2010;75(10):924-32.  [PMID:20820004]

    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.

  15. Gable MS, Gavali S, Radner A, et al. Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis. Eur J Clin Microbiol Infect Dis. 2009;28(12):1421-9.  [PMID:19718525]

    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 the concern of rabies.
    Rating: Important

  16. Loeb M, Hanna S, Nicolle L, et al. Prognosis after West Nile virus infection. Ann Intern Med. 2008;149(4):232-41.  [PMID:18711153]

    Comment: A longitudinal cohort of 156 pts. Most recovered both mental and physical function by 1 year after infection onset. The 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.

  17. Sejvar JJ. The long-term outcomes of human West Nile virus infection. Clin Infect Dis. 2007;44(12):1617-24.  [PMID:17516407]

    Comment: Subset of WNV encephalitis patients have unresolved neurological sequelae.

  18. Tauber E, Kollaritsch H, Korinek M, et al. Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial. Lancet. 2007;370(9602):1847-53.  [PMID:18061060]

    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 the current 95%) and had a good side effect profile.

  19. Domingues RB, Tsanaclis AM, Pannuti CS, et al. Evaluation of the range of clinical presentations of herpes simplex encephalitis by using polymerase chain reaction assay of cerebrospinal fluid samples. Clin Infect Dis. 1997;25(1):86-91.  [PMID:9243040]

    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.

  20. Lakeman FD, Whitley RJ. Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J Infect Dis. 1995;171(4):857-63.  [PMID:7706811]

    Comment: Study establishing PCR detection of HSV DNA as the standard for diagnosis of herpes simplex encephalitis.

  21. Poscher ME. Successful treatment of varicella zoster virus meningoencephalitis in patients with AIDS: report of four cases and review. AIDS. 1994;8(8):1115-7.  [PMID:7986408]

    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.

  22. Armstrong RW, Fung PC. Brainstem encephalitis (rhombencephalitis) due to Listeria monocytogenes: case report and review. Clin Infect Dis. 1993;16(5):689-702.  [PMID:8507761]

    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.

  23. Whitley RJ, Cobbs CG, Alford CA, et al. Diseases that mimic herpes simplex encephalitis. Diagnosis, presentation, and outcome. NIAD Collaborative Antiviral Study Group. JAMA. 1989;262(2):234-9.  [PMID:2544743]

    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.

  24. VanLandingham KE, Marsteller HB, Ross GW, et al. Relapse of herpes simplex encephalitis after conventional acyclovir therapy. JAMA. 1988;259(7):1051-3.  [PMID:3339802]

    Comment: Basis of the recommendations for treatment courses of 14-21 days with IV acyclovir.

  25. Whitley RJ, Alford CA, Hirsch MS, et al. Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med. 1986;314(3):144-9.  [PMID:3001520]

    Comment: One of two controlled trials showing a beneficial effect of acyclovir over vidarabine on mortality.

  26. CDC; Update: West Nile virus encephalitis--New York, 1999; MMWR Morb Mortal Wkly Rep; Vol. 48; pp. 944;

    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.

  27. Hardy WD, Daar ES, Sokolov RT, et al. Acute neurologic deterioration in a young man. Rev Infect Dis. 1991;13(4):745-50.  [PMID:1925293]

    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.

Last updated: January 12, 2020