Acute Infectious Encephalitis Research Articles

Outcome and Sequelae of Infectious Encephalitis.

Acute infectious encephalitis is a widely studied clinical syndrome. Although identified almost 100 years ago, its immediate and delayed consequences are still neglected despite their high frequency and possible severity. We reviewed the available data on sequelae and persisting symptoms following infectious encephalitis with the aim of characterizing the clinical picture of these patients at months to years after hospitalization. We searched PubMed for case series involving sequelae after infectious encephalitis. We carried out a narrative review of the literature on encephalitis caused by members of the Herpesviridae family (herpes simplex virus, varicella zoster virus, and human herpesvirus-6), members of the Flaviviridae family (West Nile virus, tick-borne encephalitis virus, and Japanese encephalitis virus), alphaviruses, and Nipah virus. We retrieved 41 studies that yielded original data involving 3,072 adult patients evaluated after infectious encephalitis. At least one of the five domains of cognitive outcome, psychiatric disorders, neurological deficits, global functioning, and quality of life was investigated in the reviewed studies. Various tests were used in the 41 studies and the investigation took place at different times after hospital discharge. The results showed that most patients are discharged with impairments, with frequent deficits in cognitive function such as memory loss or attention disorders. Sequelae tend to improve within several years following flavivirus or Nipah virus infection, but long-term data are scarce for other pathogens. Further research is needed to better understand the extent of sequelae after infectious encephalitis, and to propose a standardized assessment method and assess the rehabilitation efficacy in these patients.

Infectious Encephalitis in Adults: Characteristics, Outcome and Clinical Clues (S25.010)

<h3>Objective:</h3> Clinical characterization and comparison between the major causative agents of acute infectious encephalitis in adults. <h3>Background:</h3> The annual incidence of acute infectious encephalitis in adults is reported between 0.5–16 per 100,000 persons. West Nile virus (WNV) is among the most important causative agents of viral encephalitis. <h3>Design/Methods:</h3> We retrospectively characterize the clinical course of acute infectious encephalitis among adult patients admitted to the Tel-Aviv Medical Center between 2010 and 2020 (n=95), comparing major causative agents and focusing on WNV encephalitis (WNVE, n=31), varicella-zoster virus encephalitis (VZVE, n=30) and herpes simplex 1 virus encephalitis (HSV1E, n=13). <h3>Results:</h3> Patient groups differed in terms of age, with WNVE (median age 73) and VZVE (76) patients significantly older compared with HSV1E patients (51). CSF characteristics differed between groups, with VZVE patients having significant mononuclear white blood cell (WBC) predominance (99%) and HSV1E patients having lower CSF protein (57 mg/dL). Blood inflammation markers also differed significantly, with WBC higher in WNVE and C-reactive protein lower in HSV1E. Functional outcome was the worst in WNVE patients at discharge (median modified Rankin Scale [mRS] score 4) and last follow-up (median mRS score 4), reaching statistical significance when compared with VZVE patients. Differences in functional outcome prevailed when excluding patients with poor functional baseline (mRS score &gt; 2 before presentation). Logistic regression found age as an independent variable associated with worse functional outcome, and age, baseline mRS and WNVE (compared to VZVE) as associated with mortality. <h3>Conclusions:</h3> In odds with previous reports, WNVE and VZVE were far more common than HSV1E. Differences in laboratory characteristics could prove clinically useful early in the presentation of acute encephalitis. In some aspects, WNVE patients had a course resembling a bacterial, rather than viral, CNS infection. The detrimental outcome of WNVE emphasizes the need to promote solutions to WNV infection such as vaccinations and specific drugs. <b>Disclosure:</b> Dr. Maayan Eshed has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bionaut Labs Ltd. Dr. Levinson has nothing to disclose. Dr. Mina has nothing to disclose. Dr. Ashkenazi has nothing to disclose. Dr. Dekel has nothing to disclose. Dr. Cohen-Poradosu has nothing to disclose. Yifat Alcalay has nothing to disclose. Orna Aizenstein Lehavi has nothing to disclose. Yael Paran has nothing to disclose. Dr. Gadoth has received intellectual property interests from a discovery or technology relating to health care.

ENCEPHALITES AIGUES INFECTIEUSES CHEZ LENFANT, EXPERIENCE DU SERVICE DES MALADIES INFECTIEUSES DE LHOPITAL DENFANT DE RABAT

Acute infectious encephalitis is a rare neurological pathology with a varied etiology and a serious prognosis. The purpose of this work is to report the experience of the pediatric infectious diseases department of the Childrens Hospital of Rabat in the management of this condition in order to identify the clinical, paraclinical, etiological, therapeutic and evolutionary and to determine the prognostic factors. Materials and Methods: This is a retro-prospective monocentric study, conducted from January 2014 to March 2019. Included in the study are children under 15 years of age, hospitalized for acute infectious encephalitis, confirmed or retained on presumption criteria. An operating sheet has been prepared for each file collecting epidemiological, clinical, paraclinical, therapeutic and progressive data and reported in an Excel sheet. Results : 60 cases have been collected. The average age of the patients is 4 years, the sex ratio M/F is 1.14. The onset of symptoms was acute in 77% of patients. The reason for consultation was fever (78%), convulsions (63%) and febrile disturbances of consciousness (13%). On admission, functional signs were dominated by fever (90%), disturbance of consciousness (53%), immediate coma (20% of cases) and convulsions (75%). The clinical examination found signs of deficit (43.33%), meningeal syndrome (20%), gait disturbances (16.6%), aphasia (2 cases), cerebellar syndrome (2 cases) and hypotonia (3 cases). Brain CT was instrumental in the diagnosis of encephalitis (26.4%), brain MRI (70%) and EEG (51%). The CSF analysis was pathological in 46% of the cases with a positive direct examination (1 case) and positive culture at MNO (1 case). PCR on CSF was positive in 25.6% of cases (HSV1: 5cases, EBV: 1 case, TB: 4cases). The etiology found was viral (50 cases: unknown germ (42 cases), HSV1 (5 cases), chickenpox (1 case), mumps virus (1 case), EBV (1 case)) and bacterial (10 cases: unknown germ (2 cases), MNO (2 cases), PNO (1 case) BK (5 cases)). Treatment was based on the etiology. Corticotherapy was recommended for 25 children and anticonvulsant treatment in all cases. Discussion: Despite its mono-centric nature and its time limitation, this series highlight the severity of acute infectious encephalitis in children. Viral encephalitis is the most common including herpetic encephalitis. The diagnostic difficulties are significant due to the routine unavailability of cerebral MRI and PCR in the CSF. However, a probabilistic treatment must be started without delay, the time to have more elements for the etiological orientation. Physicians awareness and the availability of these examinations remain essential for obtaining better results.

Determining an infectious or autoimmune etiology in encephalitis.

ObjectivesEarly presentation and workup for acute infectious (IE) and autoimmune encephalitis (AE) are similar. This study aims to identify routine laboratory markers at presentation that are associated with IE or AE.MethodsThis was a multi‐center retrospective study at three tertiary care hospitals in New York City analyzing demographic and clinical data from patients diagnosed with definitive encephalitis based on a confirmed pathogen and/or autoantibody and established criteria for clinical syndromes.ResultsThree hundred and thirty‐three individuals with confirmed acute meningoencephalitis were included. An infectious‐nonbacterial (NB) pathogen was identified in 151/333 (45.40%), bacterial pathogen in 95/333 (28.50%), and autoantibody in 87/333 (26.10%). NB encephalitis was differentiated from AE by the presence of fever (NB 62.25%, AE 24.10%; p < 0.001), higher CSF white blood cell (WBC) (median 78 cells/μL, 8.00 cells/μL; p < 0.001), higher CSF protein (76.50 mg/dL, 40.90 mg/dL; p < 0.001), lower CSF glucose (58.00 mg/dL, 69.00 mg/dL; p < 0.001), lower serum WBC (7.80 cells/μL, 9.72 cells/μL; p < 0.050), higher erythrocyte sedimentation rate (19.50 mm/HR, 13.00 mm/HR; p < 0.05), higher C‐reactive protein (6.40 mg/L, 1.25 mg/L; p = 0.005), and lack of antinuclear antibody titers (>1:40; NB 11.54%, AE 32.73%; p < 0.001). CSF‐to‐serum WBC ratio was significantly higher in NB compared to AE (NB 11.3, AE 0.99; p < 0.001). From these findings, the association of presenting with fever, CSF WBC ≥50 cells/μL, and CSF protein ≥75 mg/dL was explored in ruling‐out AE. When all three criteria are present, an AE was found to be highly unlikely (sensitivity 92%, specificity 75%, negative predictive value 95%, and positive predictive value 64%).InterpretationsSpecific paraclinical data at initial presentation may risk stratify which patients have an IE versus AE.

Central pontine myelinolysis in the presence of SARS-CoV-2 infection (clinical observations)

Osmotic demyelinating syndrome (ODS) is a severe complication that occurs due to rapid correction of hyponatremia. Central pontine myelinolysis (CPM), in which a focus of demyelination occurs in the pontine region, and extrapontine myelinolysis (EPM), in which foci of demyelination appear in the white matter of the cerebral hemispheres, can be distinguished as a part of this syndrome. We describe two clinical cases of CPM that developed due to hyponatremia and hypokalemia in patients with SARS-CoV-2 infection (COVID-19). Differential diagnosis included acute disseminated encephalomyelitis, infectious encephalitis, and brain tumor. In both cases, a significant recovery of the lost functions was noted. The pathogenetic mechanisms of CPM development in patients with COVID-19 are discussed. ODS development in COVID- 19 necessitates strict control and correction of electrolyte disturbances in this category of patients in accordance with existing recommendations, which can reduce the risk of CPM.

Childhood Infectious Encephalitis: An Overview of Clinical Features, Investigations, Treatment, and Recent Patents.

Infectious encephalitis is a serious and challenging condition to manage. This overview summarizes the current literature regarding the etiology, clinical manifestations, diagnosis, management, and recent patents of acute childhood infectious encephalitis. We used PubMed Clinical Queries as a search engine and used keywords of "encephalitis" AND "childhood" Patents were searched using the key term "encephalitis" in google.patents.- com and patentsonline.com. Viral encephalitis is the most common cause of acute infectious encephalitis in children. In young children, the clinical manifestations can be non-specific. Provision of empiric antimicrobial therapy until a specific infectious organism has been identified, which in most cases includes acyclovir, is the cornerstone of therapy. Advanced investigation tools, including nucleic acid-based test panel and metagenomic next-generation sequencing, improve the diagnostic yield of identifying an infectious organism. Supportive therapy includes adequate airway and oxygenation, fluid and electrolyte balance, cerebral perfusion pressure support, and seizure control. Recent patents are related to the diagnosis, treatment, and prevention of acute infectious encephalitis. Viral encephalitis is the most common cause of acute infectious encephalitis in children and is associated with significant morbidity. Recent advances in understanding the genetic basis and immunological correlation of infectious encephalitis may improve treatment. Third-tier diagnostic tests may be incorporated into clinical practice. Treatment is targeted at the infectious process but remains mostly supportive. However, specific antimicrobial agents and vaccines development is ongoing.

Central nervous system infections in a tropical area: influence of emerging and rare infections.

The frequency of infectious encephalitis and the distribution of causative pathogens in tropical areas are poorly known and may be influenced by emerging and rare infections. The aim was to characterize a large series of acute infectious encephalitis and myelitis in immunocompetent patients from the Caribbean island of Guadeloupe identifying clinical, biological and radiological features according to pathogens. Using a hospital database, detailed information on a comprehensive series of immunocompetent patients with acute infectious myelitis and encephalitis over the 2012-2018 period was retrospectively collected. From 259 suspected cases with acute central nervous system infection, 171 cases were included for analysis, comprising 141 encephalitis, 22 myelitis and eight encephalomyelitis. The annual incidence peaked at 15.0/100000 during the Zika 2016 outbreak. Children accounted for 22.2% of cases. Eight adults died during hospital stay, all encephalitis. Seventeen infectious agents, two of which had never been described in Guadeloupe so far, were identified in 101 cases (59.1%), including 35 confirmed cases (34.7%), 48 probable cases (47.5%), 15 possible cases (14.9%) and three clinical cases (3.0%). The most frequent etiologic agents were Zika virus in 23 cases (13.5%), herpes simplex in 12 (7.0%), varicella zoster virus in 11 (6.4%), dengue virus in 11 (6.4%) and leptospirosis in 11 (6.4%). The Zika outbreak had a major influence on the annual incidence of acute central nervous system infection. Acute neuroleptospirosis is over-represented in our series. Further efforts are mandatory to develop new diagnostic tools for pathogen profiling.

A Prospective Cohort Study to Identify Clinical, Biological, and Imaging Features That Predict the Etiology of Acute Encephalitis

New diagnostic tools have been developed to improve the diagnosis of infectious encephalitis. Using a prospective cohort of encephalitis patients, our objective was to identify possible clusters of patients with similar patterns among encephalitis of unknown cause (EUC) and to describe to what extent a patient's initial presentation may be predictive of encephalitis etiology, particularly herpes simplex virus (HSV) and varicella-zoster virus (VZV). The National Cohort of Infectious Encephalitis in France is an ongoing prospective cohort study implemented in France in 2016. Patients who present with documented or suspected acute infectious encephalitis were included. Focusing on the variables that describe the initial presentation, we performed a factor analysis of mixed data (FAMD) to investigate a pattern of association between the initial presentation of a patient and the etiologic pathogen. As of 1 August 2018, data from 349 patients were analyzed. The most frequent pathogens were HSV (25%), VZV (11%), tick-borne encephalitis virus (6%), Listeria (5%), influenza virus (3%), and EUC (34%). Using the FAMD, it was not possible to identify a specific pattern related to the group of EUC. Age, temporal or hemorrhagic lesions, and cerebral spinal fluid lymphocytosis were significantly associated with HSV/VZV encephalitis. No initial clinical/imaging/biology pattern was identified at admission among EUC, despite the improvement in diagnostic tools. In this context, the recommendation for a universal, early, probabilistic, initial treatment against HSV and VZV is still relevant, regardless of the initial clinical presentation of the encephalitis.

Outcomes measures in children after acute central nervous system infections and malaria.

Acute central nervous system (CNS) infections in children result in significant mortality and neurologic morbidity worldwide. This article summarizes the recent pediatric literature published on outcomes measures used after acute infectious meningitis, encephalitis, and cerebral malaria, and highlights ongoing research efforts to standardize outcomes measurements. Search terms were geared toward functional, cognitive, behavioral, and other outcome assessments. Recent data suggest that, depending on microbiological cause, there are differences in currently used outcome measures following acute CNS infections. Outcomes assessments include a variety of formal psychological tests (structured interviews and neuropsychological tests of cognitive and motor functioning) and dichotomized or ordinal scales. Standardization of outcome measures, however, is lacking. Global efforts to standardize outcomes that encompass both the child and family are ongoing. Centers worldwide can track and measure a variety of cognitive, behavioral, and functional outcomes after acute CNS infections. Standardized documentation and coding of clinically important outcomes is needed. Further research to evaluate effective practices using acute adjunctive and rehabilitation therapies will be aided by outcome measure standardization.

Intensive care issues in acute encephalitis in children

Encephalitis is a major cause of acute neurological dysfunction among children and constitutes a medical emergency. Acute infectious encephalitis is usually viral in etiology. However, immune-mediated encephalitis, which are eminently treatable also forms asignificant proportion. The evaluation and management have evolved with the advances in diagnostic studies, neuromonitoring techniques and antimicrobials. Early recognition, systematic approach and institution of timely appropriate symptomatic and specific therapy are essential to improve outcomes. Cerebrospinal fluid examination and neuroimaging may point to a specific diagnosis. With few exceptions, no specific therapy is available for most forms of viral encephalitis. Morbidity and mortality can be significantly reduced in HSV encephalitis by adequate treatment with acyclovir while delays in treatment can be devastating. Long term sequelae are common among survivors.

A Cost-Effective Approach to the Diagnosis and Management of Acute Infectious Encephalitis

Setting: A tertiary care teaching hospital in India. Objective: To report a syndromic approach to acute encephalitis syndrome (AES) and propose a cost-effective model. Study design: AES patients were categorized by the presence or absence of myalgia/rash into systemic and neurological AES. The patients with systemic AES were investigated for dengue, scrub typhus, leptospira, chikungunya, and malaria, and those with neurological AES were investigated for herpes and Japanese encephalitis (JE). Sensitivity and specificity of syndromic categorization were tested, and cost effectiveness was calculated. Results: There were 210 patients with infectious AES; neurological in 45 and systemic in 165. Specific etiology could be found in 130 (62%) patients, and after excluding 36 patients with co-infections, 94 patients were tested for sensitivity and specificity. Twenty patients had neurological AES (herpes 12, JE 8), and 74 systemic (scrub typhus 42, dengue 20, malaria 6, leptospira 6). The absence of myalgia/rash categorized neurological AES with 100% specificity. In neurological AES, thalamic involvement predicted JE with 100% specificity. In systemic AES, differentiation could not be made between etiologies based on hypotension, thrombocytopenia, and muscle, liver, and kidney dysfunction. In these patients, MRI and acyclovir therapy were warranted, saving cost. By targeted investigations and treatment, the cost was reduced by 70%. Conclusions: A syndromic approach to AES and goal-directed investigations and treatment substantially reduces the cost of management.

Infectious Meningitis and Encephalitis

The clinician who is evaluating a patient with a suspected central nervous system infection often faces a large differential diagnosis. There are several signs, symptoms, geographical clues, and diagnostic testing, such as cerebrospinal fluid abnormalities and magnetic resonance imaging abnormalities, which can be helpful in identifying the etiological agent. By taking a systematic approach, one can often identify life-threatening, common, and/or treatable etiologies. Here the authors describe some of the pearls and pitfalls in diagnosing and treating acute infectious meningitis and encephalitis.

Postencephalitic Parkinsonism in a Patient with Mumps Infection: A Case Report

In 1917, Von Economo described a disease named Encephalitis Lethargica which affected a large number of patients across the world in an epidemic between 1916 and 1927. It's spread paralleled with the spread of the pandemic influenza, but Von Economo and the contemporary authors did not believe it to be a post-influenzal sequela. Now parkinsonism is a well-known complication of acute infectious encephalitis. There are many potential infectious causes of parkinsonism reported in literature. In India, postencephalitic parkinsonism is commonly due to Japanese Encephalitis. Neurologic manifestations reported in Mumps include meningitis, encephalitis, deafness, facial neuritis, cerebellar ataxia, hydrocephalus, transverse myelitis and polyradiculitis. We describe a case of young girl who had Mumps parotitis and encephalitis and then subsequently developed parkinsonism as a sequela. Mumps was confirmed by positive serology and basal ganglia lesions were demonstrated by magnetic resonance imaging of the brain. To the best of our knowledge, this is the first case of postencephalitic parkinsonism following Mumps infection from India.

What is new about epidemiology of acute infectious encephalitis?

This review aims to describe new features on the epidemiology of encephalitis world-wide. As this neurological presentation is most frequently related to transmitted viruses, surveillance of encephalitis is of major importance to detect their emergence or re-emergence. Rabies causes one of the most severe types of encephalitis as it is lethal in all cases, and it is endemic in some countries. It was thought that the virus had been eradicated in Western Europe, but it re-emerged in Greece and Italy. Physicians should be aware of this diagnosis in the case of severe encephalitis. Some viruses (Powassan, Nipah, and Hendra) are becoming endemic in some new parts of the world (USA and Australia). Because of their severity, they are healthcare concerns in those countries and for travelers (e.g. in Asia). Finally, a concept is emerging: herpes simplex virus is suspected to be a trigger for autoimmune encephalitis. This is of major importance for the future management of patients (corticosteroids early in the course of the disease?), and the epidemiology of sequelae. Encephalitis is a good marker for the detection of emerging infections. New findings about the relationship between herpes simplex virus encephalitis and autoimmune encephalitis open a new concept for a better management of patients.

Steroids and Childhood Encephalitis

G (GS) have both antiinflammatory and immunosuppressive property, which explains why pediatricians tend to prescribe them for all pediatric clinical conditions in which it is thought or known that inflammation and/or autoimmunity are the main cause of disease signs and symptoms. However, such prescriptions are sometimes questionable because the efficacy of GS has not been demonstrated by controlled trials, and the risk of adverse events following high-dose or prolonged administration has not been adequately evaluated. Encephalitis is one of the syndromes for which GS are frequently used. However, the importance of this treatment remains unclear because a diagnosis of encephalitis covers a range of clinical conditions whose etiology, pathogenesis, clinical picture and spontaneous evolution vary. Furthermore, it has been tested in very few studies involving children. The aim of this article is to review what is currently known about the real impact of GS treatment in children with acute infectious encephalitis (AIE) and acute disseminated encephalomyelitis (ADEM), the 2 major types of encephalitis.

Long-term Outcome of Patients Presenting With Acute Infectious Encephalitis of Various Causes in France

A prospective study of infectious encephalitis was conducted in France in 2007. In total, 253 patients were enrolled with a proven etiological diagnosis for 52%. The cohort of surviving patients with encephalitis was assessed for sequelae and impairment 3 years after enrollment. Patients, their family, and general practitioners (GPs) were interviewed by phone to document persisting symptoms, return to work, and past and current leisure activities, with standardized questionnaires. The IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) was completed with relatives. The global outcome was determined in all patients with the Glasgow outcome scale. In 2010, 20 patients (10%) were unavailable for follow-up, 2 (1%) were excluded, and 18 (9%) had died since hospital discharge. Data were available for 167 survivors and 9 patients whose death was related to the encephalitis. The outcome was favorable in 108 of 176 patients (61%) (71 with complete resolution), 31 (18%) were mildly impaired, 25 (14%) were severely impaired, and 3 (1%) were in a vegetative state. The most frequent symptoms were difficulty concentrating (42%), behavioral disorders (27%), speech disorders (20%), and memory loss (19%). Fifteen of 63 patients (24%) previously employed were still unable to resume work. Long-term outcome was significantly associated with comorbid conditions, age, level of education, and the causative agent of encephalitis. Most patients with encephalitis experienced a favorable outcome 3 years after hospital discharge. However, minor to severe disability persists in a high number of cases with consequences for everyday life. Physical and mental impairment should be evaluated in all patients with encephalitis, and neuropsychological rehabilitation implemented whenever needed.

Encephalitis in the Pediatric Population

1. Stephen J. Falchek, MD* 1. *Division of Pediatric Neurology, Alfred I. duPont Hospital for Children/Thomas Jefferson University, Wilmington, DE, and Philadelphia, PA. * Abbreviations: ADEM: : acute disseminated encephalomyelitis CEP: : California Encephalitis Project CNS: : central nervous system CPP: : cerebral perfusion pressure CSF: : cerebrospinal fluid HSV: : herpes simplex virus IVIG: : intravenous immune globulin MS: : multiple sclerosis PCR: : polymerase chain reaction WNV: : West Nile virus Management of encephalitis, which can be fatal, requires understanding of a broad range of causative agents, pathophysiologic mechanisms, clinical syndromes, and outcomes. After completing this article, readers should be able to: 1. Know the many causes of encephalitis, including infectious, parainfectious, and noninfectious disorders. 2. Recognize the clinical features of encephalitis. 3. Be able to conduct a diagnostic investigation of a patient with encephalitis by using clinical and laboratory criteria. 4. Know the anticipated clinical course of different types of encephalitis. 5. Be familiar with the modalities used to treat encephalitis. 6. Understand the factors that influence the outcome in a patient who has encephalitis. The broad definition of the term “encephalitis,” that is, inflammation of the brain , necessitates acknowledgment of the enormous inclusivity of the topic. The most common interpretation of the term implies a direct invasion of the brain by an infectious pathogen, most commonly, viral, fungal, or parasitic. The topic also includes examples of meningitis mediated by bacteria or other agents, which can produce extrameningeal symptoms such as lethargy or seizures, in which case, the combined term “meningoencephalitis” is used. There are also many examples of encephalitis not due to direct central nervous system (CNS) infections. Inflammatory processes due to an acute or chronic illness can result in an acute immune-mediated encephalitis, such as acute disseminated encephalomyelitis (ADEM), lupus cerebritis, and paraneoplastic syndromes. Agents or conditions that produce slowly progressive CNS symptoms, such as tertiary syphilis or “slow viruses” (the prion protein encephalopathies), also are considered examples of encephalitis. Table 1 lists only a limited number of the many pathogens and pathologic conditions that can cause either acute or subacute encephalitis. In this discussion, …

Infectious Encephalitis in France in 2007: A National Prospective Study

Encephalitis is associated with significant mortality and morbidity, but its cause remains largely unknown. We designed a national prospective study in France in 2007 to describe patients with encephalitis, investigate the etiologic diagnosis of encephalitis, and assess risk factors associated with death. Patients were enrolled by attending physicians according to case definition, and data were collected with a standardized questionnaire. The etiologic diagnosis was investigated after a standardized procedure. Risk factors associated with death during hospitalization were assessed by multivariate logistic regression. A total of 253 patients with acute infectious encephalitis from 106 medical units throughout France were included in the study. Their ages ranged from 1 month to 89 years (median age, 54 years); 61% were male. Cause of the encephalitis was determined in 131 patients (52%). Herpes simplex virus 1 (42%), varicella-zoster virus (15%), Mycobacterium tuberculosis (15%), and Listeria monocytogenes (10%) were the most frequently identified agents. Twenty-six patients (10%, all adults) died, 6 of them with tuberculosis and 6 with listeriosis. Risk factors independently associated with death during hospitalization identified by the multivariable analysis were age (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0-1.4; for 5-year increase), cancer (OR, 17; 95% CI, 2.3-122.6), immunosuppressive treatment before onset (OR, 24; 95% CI, 1.3-426.0), percentage of hospitalized patients receiving mechanical ventilation (OR, 2.0; 95% CI, 1.4-3.0; for 10% increase), the etiologic agent, coma on day 5 after admission (OR, 16; 95% CI, 2.8-92.3), and sepsis on day 5 after admission (OR, 94; 95% CI, 4.9-1792.2). Our prospective study provides an overview of the clinical and etiologic patterns of acute infectious encephalitis in adults in France. Herpes simplex virus 1 remains the main cause of encephalitis, but bacteria accounts for the highest case-fatality rates.

Acute infectious encephalitis and pathogens coming from animals

Despite better knowledge of pathophysiology and a wider use of new molecular technologies for the diagnosis, the etiological diagnosis of acute encephalitis is not established in most cases. Incidence, prognosis, rate of this disease and severity of sequelae remain unknown. In France, according to the published data, the incidence of encephalitis is estimated to be 1.9 cases per 100 000 inhabitants in average among non-HIV patients. The etiological diagnosis is established in less than 30% of cases. The more frequent diagnosis is herpetic encephalitis in adults and encephalitis caused by Varicella zoster virus in children younger than 16 years. Despite a difficult diagnosis and the lack of specific treatment for most of these infections, the etiological diagnosis should always be deeply explored to precise the individual prognosis, to allow better management of antibiotic therapy, and to improve epidemiological knowledge. We present the recommendations established by the French Society for Infectious Diseases. First designed to suit the French epidemiology, they take in count the possible exposure of patients to different epidemiological patterns. Three levels of etiological tests are proposed, from the most common infections and those, which required an immediate treatment, to the rarest ones.

A medical overview of encephalitis

Encephalitis is uncommon but is a neurological emergency which must be considered in a patient presenting with altered consciousness. Encephalitis is a diffuse inflammatory process of the brain parenchyma associated with evidence of brain dysfunction. The presentation of encephalitis can be acute or chronic. The aetiology of encephalitis can be broadly divided into two major subtypes. (1) Infection-related encephalitis which is a direct consequence of pathogenic viral, bacterial or parasitic agents. Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are the most common cause of acute infectious encephalitis. (2) Autoimmune-mediated encephalitis which is mediated by an aberrant immune response. This can be triggered by a recent viral infection or vaccination. An example of this would be acute disseminated encephalitis (ADEM). This article will focus on the medical management of acute encephalitis. This will involve an extensive overview of the literature reviewing the diagnosis, investigation and treatment of acute viral encephalitis, ADEM and acute haemorrhagic leukoencephalopathy (AHLE). Encephalitis can also present chronically, and some of the different types of chronic encephalitis will be discussed.