Comparative Study

Authors: Divyanshu Dubey, Sean J Pittock, Cecilia R Kelly...

OBJECTIVE

To evaluate the incidence and prevalence of autoimmune encephalitis and compare it to that of infectious encephalitis.

METHODS

We performed a population-based comparative study of the incidence and prevalence of autoimmune and infectious encephalitis in Olmsted County, Minnesota. Autoimmune encephalitis diagnosis and subgroups were defined by 2016 diagnostic criteria, and infectious encephalitis diagnosis required a confirmed infectious pathogen. Age- and sex-adjusted prevalence and incidence rates were calculated. Patients with encephalitis of uncertain etiology were excluded.

RESULTS

The prevalence of autoimmune encephalitis on January 1, 2014 of 13.7/100,000 was not significantly different from that of all infectious encephalitides (11.6/100,000; p = 0.63) or the viral subcategory (8.3/100,000; p = 0.17). The incidence rates (1995-2015) of autoimmune and infectious encephalitis were 0.8/100,000 and 1.0/100,000 person-years, respectively (p = 0.58). The number of relapses or recurrent hospitalizations was higher for autoimmune than infectious encephalitis (p = 0.03). The incidence of autoimmune encephalitis increased over time from 0.4/100,000 person-years (1995-2005) to 1.2/100,000 person-years (2006-2015; p = 0.02), attributable to increased detection of autoantibody-positive cases. The incidence (2.8 vs 0.7/100,000 person-years, p = 0.01) and prevalence (38.3 vs 13.7/100,000, p = 0.04) of autoimmune encephalitis was higher among African Americans than Caucasians. The prevalence of specific neural autoantibodies was as follows: myelin oligodendrocyte glycoprotein, 1.9/100,000; glutamic acid decarboxylase 65, 1.9/100,000; unclassified neural autoantibody, 1.4/100,000; leucine-rich glioma-inactivated protein 1, 0.7/100,000; collapsin response-mediator protein 5, 0.7/100,000; N-methyl-D-aspartate receptor, 0.6/100,000; antineuronal nuclear antibody type 2, 0.6/100,000; and glial fibrillary acidic protein α, 0.6/100,000.

INTERPRETATION

This study shows that the prevalence and incidence of autoimmune encephalitis are comparable to infectious encephalitis, and its detection is increasing over time. Ann Neurol 2018;83:166-177.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Black People; Child; Child, Preschool; Encephalitis; Female; Hashimoto Disease; Hospitalization; Humans; Incidence; Infant; Infant, Newborn; Infectious Encephalitis; Male; Middle Aged; Prevalence; Recurrence; United States; White People; Young Adult; Black or African American

PubMed: 29293273
DOI: 10.1002/ana.25131

Review

Authors: Bruna Klein da Costa, Douglas Kazutoshi Sato

OBJECTIVES

To review the diagnostic criteria for encephalitis and encephalopathy of presumed infectious etiology, as well as the diagnostic workup for viral encephalitis and its treatment approaches. The authors also intended to summarize relevant information on specific viruses frequently found in Brazil.

SOURCE OF DATA

Literature search on Pubmed/MEDLINE using the following keywords: "viral", "encephalitis", "child", or "adolescents", filtering for articles on humans and in English.

SUMMARY OF DATA

Viral encephalitis is the most common cause of encephalitis and is responsible for high rates of morbidity, permanent neurologic sequelae, and according to the virus, may have high mortality rates. The most common etiologies are herpesviruses 1 and 2 (HSV-1 and HSV-2), non-polio enterovirus, and arboviruses (in Brazil, dengue, Zika, and chikungunya). Other relevant etiologies are seasonal influenza, cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and the re-emergent measles.

CONCLUSION

Clinical data, laboratory results, and neuroimaging findings support the diagnosis of encephalitis and the specific viral etiology. To increase the likelihood of etiologic confirmation, it is important to know the best approach to collecting samples and to choose the best identification technique for each virus. The differential diagnosis of viral encephalitis includes other infections and immune-mediated inflammatory central nervous system disorders.

Topics: Adolescent; Brazil; Child; Cytomegalovirus; Encephalitis, Viral; Herpesvirus 4, Human; Herpesvirus 6, Human; Humans; Zika Virus; Zika Virus Infection

PubMed: 31513761
DOI: 10.1016/j.jped.2019.07.006

Review

Authors: Sang-Im Yun, Young-Min Lee

Japanese encephalitis (JE) is an infectious disease of the central nervous system caused by Japanese encephalitis virus (JEV), a zoonotic mosquito-borne flavivirus. JEV is prevalent in much of Asia and the Western Pacific, with over 4 billion people living at risk of infection. In the absence of antiviral intervention, vaccination is the only strategy to develop long-term sustainable protection against JEV infection. Over the past half-century, a mouse brain-derived inactivated vaccine has been used internationally for active immunization. To date, however, JEV is still a clinically important, emerging, and re-emerging human pathogen of global significance. In recent years, production of the mouse brain-derived vaccine has been discontinued, but 3 new cell culture-derived vaccines are available in various parts of the world. Here we review current aspects of JEV biology, summarize the 4 types of JEV vaccine, and discuss the potential of an infectious JEV cDNA technology for future vaccine development.

Topics: Animals; Asia; Cell Line; Drug Discovery; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Japanese Encephalitis Vaccines; Technology, Pharmaceutical; Vaccination

PubMed: 24161909
DOI: 10.4161/hv.26902

Review

Authors: Julia C Haston, Jennifer R Cope

PURPOSE OF REVIEW

Free-living amebae (FLA) including Naegleria fowleri , Balamuthia mandrillaris , and Acanthamoeba species can cause rare, yet severe infections that are nearly always fatal. This review describes recent developments in epidemiology, diagnosis, and treatment of amebic meningoencephalitis.

RECENT FINDINGS

Despite similarities among the three pathogenic FLA, there are notable variations in disease presentations, routes of transmission, populations at risk, and outcomes for each. Recently, molecular diagnostic tools have been used to diagnose a greater number of FLA infections. Treatment regimens for FLA have historically relied on survivor reports; more data is needed about novel treatments, including nitroxoline.

SUMMARY

Research to identify new drugs and guide treatment regimens for amebic meningoencephalitis is lacking. However, improved diagnostic capabilities may lead to earlier diagnoses, allowing earlier treatment initiation and improved outcomes. Public health practitioners should continue to prioritize increasing awareness and providing education to clinicians, laboratorians, and the public about amebic infections.

Topics: Humans; Central Nervous System Protozoal Infections; Amebiasis; Meningoencephalitis; Acanthamoeba; Infectious Encephalitis

PubMed: 37093056
DOI: 10.1097/QCO.0000000000000923

Review

Authors: Lyle R Petersen, Aaron C Brault, Roger S Nasci...

IMPORTANCE

Since its introduction in North America in 1999, West Nile virus has produced the 3 largest arboviral neuroinvasive disease outbreaks ever recorded in the United States.

OBJECTIVE

To review the ecology, virology, epidemiology, clinical characteristics, diagnosis, prevention, and control of West Nile virus, with an emphasis on North America.

EVIDENCE REVIEW

PubMed electronic database was searched through February 5, 2013. United States national surveillance data were gathered from the Centers for Disease Control and Prevention.

FINDINGS

West Nile virus is now endemic throughout the contiguous United States, with 16,196 human neuroinvasive disease cases and 1549 deaths reported since 1999. More than 780,000 illnesses have likely occurred. To date, incidence is highest in the Midwest from mid-July to early September. West Nile fever develops in approximately 25% of those infected, varies greatly in clinical severity, and symptoms may be prolonged. Neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis) develops in less than 1% but carries a fatality rate of approximately 10%. Encephalitis has a highly variable clinical course but often is associated with considerable long-term morbidity. Approximately two-thirds of those with paralysis remain with significant weakness in affected limbs. Diagnosis usually rests on detection of IgM antibody in serum or cerebrospinal fluid. Treatment is supportive; no licensed human vaccine exists. Prevention uses an integrated pest management approach, which focuses on surveillance, elimination of mosquito breeding sites, and larval and adult mosquito management using pesticides to keep mosquito populations low. During outbreaks or impending outbreaks, emphasis shifts to aggressive adult mosquito control to reduce the abundance of infected, biting mosquitoes. Pesticide exposure and adverse human health events following adult mosquito control operations for West Nile virus appear negligible.

CONCLUSIONS AND RELEVANCE

In North America, West Nile virus has and will remain a formidable clinical and public health problem for years to come.

Topics: Animals; Birds; Culicidae; Ecology; Humans; Mosquito Control; United States; West Nile Fever; West Nile virus

PubMed: 23860989
DOI: 10.1001/jama.2013.8042

Review

Authors: Jocelyne Piret, Guy Boivin

Herpes simplex virus 1 (HSV-1) can be responsible for life-threatening HSV encephalitis (HSE). The mortality rate of patients with HSE who do not receive antiviral treatment is 70%, with most survivors suffering from permanent neurological sequelae. The use of intravenous acyclovir together with improved diagnostic technologies such as PCR and magnetic resonance imaging has resulted in a reduction in the mortality rate to close to 20%. However, 70% of surviving patients still do not recover complete neurological functions. Thus, there is an urgent need to develop more effective treatments for a better clinical outcome. It is well recognized that cerebral damage resulting from HSE is caused by viral replication together with an overzealous inflammatory response. Both of these processes constitute potential targets for the development of innovative therapies against HSE. In this review, we discuss recent progress in therapy that may be used to ameliorate the outcome of patients with HSE, with a particular emphasis on immunomodulatory agents. Ideally, the administration of adjunctive immunomodulatory drugs should be initiated during the rise of the inflammatory response, and its duration should be limited in time to reduce undesired effects. This critical time frame should be optimized by the identification of reliable biomarkers of inflammation.

Topics: Acyclovir; Adrenal Cortex Hormones; Animals; Antiviral Agents; Drug Therapy; Encephalitis, Herpes Simplex; Genetic Predisposition to Disease; Humans; Immunity; Immunomodulation; Risk Factors; Simplexvirus; Treatment Outcome

PubMed: 32051176
DOI: 10.1128/CMR.00105-19

Review

Authors: Maria D Mileno

Travelers to 24 endemic countries in Asia may be at risk for Japanese encephalitis. The ACIP has recently expanded guidelines on the use of Ixiaro, the inactivated Japanese encephalitis vaccine. This article reviews the disease burden of Japanese encephalitis and the role of a travel clinic in guiding travelers to Asia regarding decision-making about the use of this highly protective vaccine.

Topics: Adolescent; Adult; Asia; Child; Child, Preschool; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Infant; Japanese Encephalitis Vaccines; Risk; Seasons; Travel

PubMed: 32752568
DOI: No ID Found

Authors: Léa Poussier, Alexandra Mailles, Pierre Tattevin...

OBJECTIVE

To characterize differences between Herpes Simplex virus encephalitis and Varicella-Zoster virus encephalitis (HSVE and VZVE) and other aetiologies of infectious encephalitis (IE), and to investigate the impact of time-to-aciclovir (ACV) start, ACV dose and duration on outcome.

METHODS

We compared 132 HSVE, 65 VZVE and 297 other IE enrolled in a prospective cohort (ENCEIF). We estimated associations between time-to-ACV start, dose or duration and outcome through adjusted odds ratio (aOR) using logistic regression analysis.

RESULTS

Prevalence of immunodepression differed among aetiologies: 15/65 (23%) for VZVE, 13/132 (10%) for HSVE and 30/297 (10%) for other IE (p <0.05), as was presence of seizure at admission: 27/132 (20%) for HSVE, 4/65 (6%) for VZVE and 43/297 (14%) for other IE (p <0.05). Poor outcome at hospital discharge (Glasgow outcome scale ≤3) differed among the three groups: 40/127 (31%) for HSVE, 12/65 (18%) for VZVE and 38/290 (13%) for other IE (p <0.05). Time-to-ACV start was associated with outcome in HSVE (aOR 3.61 [1.25-10.40]), but not in VZVE (aOR 0.84 [0.18-3.85]). Increased ACV dose was not associated with outcome among HSVE (aOR 1.25 [0.44-3.64]) nor VZVE (aOR 1.16 [0.24-5.73]).

DISCUSSION

HSVE and VZVE are distinct in clinical presentation, outcome and prognostic factors. The impact of early ACV initiation was more apparent for HSVE than for VZVE; however, this could be because of VZVE's smaller sample size and lower outcome rate leading to low statistical power or because of potential distinct IE pathophysiology.

Topics: Humans; Prospective Studies; Male; Female; Middle Aged; Antiviral Agents; Acyclovir; Aged; Encephalitis, Herpes Simplex; Encephalitis, Varicella Zoster; Treatment Outcome; Adult; Herpesvirus 3, Human; Young Adult; Adolescent; Aged, 80 and over

PubMed: 38527616
DOI: 10.1016/j.cmi.2024.03.017

Meta-Analysis

Authors: Emira Hodzic, Rodrigo Hasbun, Alejandro Granillo...

BACKGROUND

Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its utility. We present a systematic review and meta-analysis on the outcome of steroid use in VE.

METHODS

We conducted a systematic literature review and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two observational studies from unpublished or partially published data were added. For the meta-analysis, we employed the metaphor package of the statistical software R-4.3.1.

RESULTS

We screened 378 studies and included 50. 155 patients were added from the Houston and Linz cohorts. Individual data were available for 281 persons, 120 (43%) of whom received steroids. The most common pathogens were herpes simplex virus 1, West Nile virus, and measles. Study designs and patient outcomes were heterogeneous. Only three of the trials report an advantage of steroid therapy. Steroid-induced side effects were scarce. Ten cohorts were included into the meta-analysis. For the pooled data, the null hypothesis could not be rejected (p = 0.245) using a random effects model, i.e., a benefit of steroid treatment on survival in VE could not be shown.

CONCLUSIONS

Steroids as potent anti-inflammatory agents may act through a reduction of secondary inflammation-mediated damage. Our data do not support the use of steroids in VE. However, multiple shortcomings apply. Standardized controlled trials are needed to investigate optimal dosing and timing of steroid administration and to explore potential subgroups that could benefit.

Topics: Humans; Steroids; Anti-Inflammatory Agents; Encephalitis, Viral

PubMed: 37060361
DOI: 10.1007/s00415-023-11715-0

Authors: Tobias Moser, Joachim Gruber, Eirini Mylonaki...

BACKGROUND

Encephalitis originates from diverse autoimmune and infectious etiologies. Diagnostic challenges arise due to the spectrum of presentation and the frequent absence of specific biomarkers. This study aimed to comprehensively characterize and differentiate autoimmune encephalitis (AE) from infectious encephalitis (IE) in adults, and disentangle clinical, paraclinical, and therapeutic differences.

METHODS

A cohort study spanning 10 years was conducted across three Austrian tertiary care hospitals. Inclusion criteria comprised adults with probable or definite encephalitis. Demographics, clinical features, technical findings, treatment modalities, and outcomes were collected from the electronic patient files. A follow-up was performed via telephone interviews and clinical visits.

RESULTS

Of 149 patients, 17% had AE, 73% IE, and 10% encephalitis of unknown etiology. Significant differences between AE and IE included the prevalence of acute symptomatic seizures (AE: 85% vs. IE: 20%, p < 0.001), fever (8% vs. 72%, p < 0.001), headache (15% vs. 61%, p < 0.001), and focal neurological deficits (56% vs. 23%, p = 0.004), respectively. Paraclinical differences comprised lower CSF pleocytosis in AE compared to IE (median 6 cells/µl vs. 125 cells/µl, p < 0.001). Epileptic discharges on EEG and MRI lesions were more prevalent in AE than IE (50% vs. 14%, p < 0.001; 50% vs. 28%, p = 0.037). The modified Rankin Scale scores at discharge and last follow-up (median duration 2304 days, IQR 1433-3274) indicated favorable outcomes in both groups.

CONCLUSION

This comprehensive analysis provides insights into the epidemiology, clinical, paraclinical, and therapeutic aspects and the outcomes of AE and IE in adults. We developed a diagnostic tool that facilitates early differentiation between AE and IE, aiding in timely therapeutic decision-making.

Topics: Humans; Male; Female; Middle Aged; Encephalitis; Adult; Aged; Early Diagnosis; Infectious Encephalitis; Cohort Studies; Hashimoto Disease; Diagnosis, Differential; Electroencephalography; Magnetic Resonance Imaging; Follow-Up Studies

PubMed: 39368009
DOI: 10.1007/s00415-024-12712-7