Viral encephalitis: a clinician’s guide
TL;DR: The Liverpool approach to the investigation and treatment of adults with suspected viral encephalitis is discussed, and the Liverpool algorithm for investigation and Treatment of immunocompetent adults with suspicions of viral encephalitis is introduced.
Abstract: The management of patients with suspected viral encephalitis has been revolutionised in recent years with improved imaging and viral diagnostics, better antiviral and immunomodulatory therapies, and enhanced neurointensive care. Despite this, disasters in patient management are sadly not uncommon. While some patients are attacked with all known antimicrobials with little thought to investigation of the cause of their illness, for others there are prolonged and inappropriate delays before treatment is started. Although viral encephalitis is relatively rare, patients with suspected central nervous system (CNS) infections, who might have viral encephalitis, are not. In addition, the increasing number of immunocompromised patients who may have viral CNS infections, plus the spread of encephalitis caused by arthropod-borne viruses, present new challenges to clinicians. This article discusses the Liverpool approach to the investigation and treatment of adults with suspected viral encephalitis, and introduces the Liverpool algorithm for investigation and treatment of immunocompetent adults with suspected viral encephalitis (available at www.liv.ac.uk/braininfections).
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TL;DR: A group of clinicians met in Liverpool in February 2008 to begin the development process for clinical care guidelines based around a similar simple algorithm, supported by an evidence base, whose implementation is hoped would improve the management of patients with suspected encephalitis.
312 citations
Cites background from "Viral encephalitis: a clinician’s g..."
...However, as HSV encephalitis is more common in the elderly than younger adults, it is especially important that the diagnosis is considered promptly in such patients.(36)...
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...Recommendations All patients with suspected encephalitis should have a CSF PCR test for HSV (1 and 2), VZV and enteroviruses, as this will identify 90% of cases due to known viral pathogens (B, II) Further testing should be directed towards specific pathogens as guided by the clinical features, such as occupation, travel history and animal or insect contact (B, III) Evidence Although the list of viral causes of encephalitis is long, HSV 1 & 2, VZV and enteroviruses are the most commonly identified causes of viral encephalitis in immunocompetent individuals in Europe & the United States.5,36,56,57 Our ability to diagnose encephalitis caused by herpes viruses & enteroviruses has been improved greatly by developments in PCR methods.58,59 CSF PCR for HSV between day 2 and10 of illness has overall sensitivity and specificity of >95% for HSV encephalitis in immunocompetent adults.11,28 Although HSV PCR may be negative in the first few days of the illness. a second CSF taken 3e7 days later will often be HSV positive, even if aciclovir treatment has been started.12,59,60 Further microbiological investigations should be based on specific epidemiological factors (age; animal, insect, and sexual contacts; immune status; occupation; recreational activities; geography and a recent travel history; season of the year; and vaccination history) and clinical findings (hepatitis, lymphadenopathy, rash, respiratory tract infection, retinitis, urinary symptoms and neurological syndrome (Table 11)....
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...Microbiological investigation of encephalitis).(36,50,61,62)...
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...individuals in Europe & the United States.(5,36,56,57) Our ability to diagnose encephalitis caused by herpes viruses & enteroviruses has been improved greatly by developments in PCR methods....
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...2007).(35,36) Note viral causes of chronic encephalitis such as JC viruses are not included here....
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TL;DR: A national prospective study in France in 2007 to investigate the etiologic diagnosis of encephalitis, investigate the risk factors associated with death, and assess risk factors related to death found bacteria accounts for the highest case-fatality rates.
Abstract: Background 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. Methods 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. Results 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). Conclusions 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.
297 citations
Additional excerpts
...vascular disorders, or infectious diseases [2]....
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TL;DR: The pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults in adults are reviewed, including a discussion of the most common complications and their treatment.
268 citations
25 Oct 2008
TL;DR: The cause of encephalitis is associated with significant mortality and morbidity, but its cause remains largely unknown as discussed by the authors, and the etiologic diagnosis and risk factors associated with death during hospitalization were assessed by multivariate logistic regression.
Abstract: BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSIONS
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.
261 citations
TL;DR: Prospective studies are required to document the risk of late unprovoked seizures and epilepsy following viral encephalitis due to different viruses as well as to determine the clinical characteristics, course, and outcome of post‐encephalitic epilepsy.
Abstract: Viral encephalitis presents with seizures not only in the acute stage but also increases the risk of late unprovoked seizures and epilepsy. Acute symptomatic and late unprovoked seizures in different viral encephalitides are reviewed here. Among the sporadic viral encephalitides, Herpes simplex encephalitis (HSE) is perhaps most frequently associated with epilepsy, which may often be severe. Seizures may be the presenting feature in 50% patients with HSE because of involvement of the highly epileptogenic frontotemporal cortex. The occurrence of seizures in HSE is associated with poor prognosis. In addition, chronic and relapsing forms of HSE have been described and these may be associated with antiepileptic drug-resistant seizures. Among the epidemic (usually due to flaviviruses) viral encephalitides, Japanese encephalitis (JE) is most common and is associated with acute symptomatic seizures, especially in children. The reported frequency of acute symptomatic seizures in JE is 7-46%. Encephalitis due to other flaviviruses such as equine, St. Louis, and West Nile viruses may also manifest with acute symptomatic seizures. In Nipah virus encephalitis, seizures are more common in relapsed and late-onset encephalitis in comparison to acute encephalitis (4% vs. 1.8%). Other viruses like measles, varicella, mumps, influenza, and entero-viruses may cause seizures depending on the area of brain involved. There is no comprehensive data regarding late unprovoked seizures in different viral encephalitides. Prospective studies are required to document the risk of late unprovoked seizures and epilepsy following viral encephalitis due to different viruses as well as to determine the clinical characteristics, course, and outcome of post-encephalitic epilepsy.
178 citations
References
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TL;DR: VGKC-Ab-associated encephalopathy is a relatively common form of autoimmune, non-paraneoplastic, potentially treatable encephalitis that can be diagnosed by a serological test.
Abstract: Patients presenting with subacute amnesia are frequently seen in acute neurological practice. Amongst the differential diagnoses, herpes simplex encephalitis, Korsakoff's syndrome and limbic encephalitis should be considered. Limbic encephalitis is typically a paraneoplastic syndrome with a poor prognosis; thus, identifying those patients with potentially reversible symptoms is important. Voltage-gated potassium channel antibodies (VGKC-Ab) have recently been reported in three cases of reversible limbic encephalitis. Here we review the clinical, immunological and neuropsychological features of 10 patients (nine male, one female; age range 44-79 years), eight of whom were identified in two centres over a period of 15 months. The patients presented with 1-52 week histories of memory loss, confusion and seizures. Low plasma sodium concentrations, initially resistant to treatment, were present in eight out of 10. Brain MRI at onset showed signal change in the medial temporal lobes in eight out of 10 cases. Paraneoplastic antibodies were negative, but VGKC-Ab ranged from 450 to 5128 pM (neurological and healthy controls <100 pM). CSF oligoclonal bands were found in only one, but bands matched with those in the serum were found in six other patients. VGKC-Abs in the CSF, tested in five individuals, varied between <1 and 10% of serum values. Only one patient had neuromyotonia, which was excluded by electromyography in seven of the others. Formal neuropsychology testing showed severe and global impairment of memory, with sparing of general intellect in all but two patients, and of nominal functions in all but one. Variable regimes of steroids, plasma exchange and intravenous immunoglobulin were associated with variable falls in serum VGKC-Abs, to values between 2 and 88% of the initial values, together with marked improvement of neuropsychological functioning in six patients, slight improvement in three and none in one. The improvement in neuropsychological functioning in seven patients correlated broadly with the fall in antibodies. However, varying degrees of cerebral atrophy and residual cognitive impairment were common. Over the same period, only one paraneoplastic case of limbic encephalitis was identified between the two main centres. Thus, VGKC-Ab-associated encephalopathy is a relatively common form of autoimmune, non-paraneoplastic, potentially treatable encephalitis that can be diagnosed by a serological test. Establishing the frequency of this new syndrome, the full range of clinical presentations and means of early recognition, and optimal immunotherapy, should now be the aim.
971 citations
"Viral encephalitis: a clinician’s g..." refers background in this paper
...paraneoplastic limbic encephalitis, and voltage gated potassium channel limbic encephalitis.(1)...
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TL;DR: It is concluded that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis and patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acy Clovir treatment.
Abstract: We randomly assigned 208 patients who underwent brain biopsy for presumptive herpes simplex encephalitis to receive either vidarabine (15 mg per kilogram of body weight per day) or acyclovir (30 mg per kilogram per day) for 10 days. Sixty-nine patients (33 percent) had biopsy-proved disease; 37 received vidarabine, and 32 acyclovir. The mortality in the vidarabine recipients was 54 percent, as compared with 28 percent in the acyclovir recipients (P = 0.008). Six-month mortality varied according to the Glasgow coma score at the onset of therapy. For scores of greater than 10, 7 to 10, and less than or equal to 6, mortality was 42, 46, and 67 percent in the patients treated with vidarabine, as compared with 0, 25, and 25 percent in those treated with acyclovir. A six-month morbidity assessment using an adapted scoring system revealed that 5 of 37 patients receiving vidarabine (14 percent) as compared with 12 of 32 receiving acyclovir (38 percent) were functioning normally (P = 0.021). Eight vidarabine-treated patients (22 percent) and three acyclovir-treated patients (9 percent) had moderate debility. Patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acyclovir treatment. We conclude that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis.
772 citations
Book•
21 Apr 2014TL;DR: The central nervous system syndromes mediated by bacterial toxins: botulism, J.J. Whitley and S. Stagno neurological manifestations of infection with the human immunodeficiency viruses, B.K. Plotkin Guillain-Barre syndrome and D.G. McLone.
Abstract: Part 1 Viral infections of the central nervous system and related disorders: pathogenesis and pathophysiology of viral infections of the central nervous system, M. Schlitt et al viral meningitis and the aseptic meningitis syndrom, H.A. Rotbart encephalitis caused by herpesviruses, including B virus, R.J. Whitley and M. Schlitt arthropod-borne encephalitides, R.J. Whitley meningitis and encephalitis caused by mumps virus, J.W. Gnann, Jr et al slow viral infections of the human nervous system, D.M. Asher perinatal viral infections R.J. Whitley and S. Stagno neurological manifestations of infection with the human immunodeficiency viruses, B.K. Evans et al viral vaccines that protect the central nervous system, M.F. Mangano and S.A. Plotkin Guillain-Barre syndrome, G. Tenorio et al. Part 2 Mycoplasmal infections of the central nervous system: mycoplasmal diseases of the central nervous system, W.A. Clyde, Jr. Part 3 Bacterial infections of the central nervous system: pathogenesis and pathophysiology of bacterial infections of the central nervous system, A.R. Tunkel and W.M. Scheld neonatal bacterial meningitis, A.L. Smith and J. Haas acute bacterial meningitis in children and adults, K.L. Roos et al rickettsiae and the central nervous system, J.H. Kim and D.T. Durack tuberculosis of the central nervous system, A. Zuger and F.D. Lowy brain abscess, B. Wispelwey et al subdural empyema, D.C. Hefgott et al epidural abscess, B.G. Gellin et al central nervous system complications of infective endocarditis, P. Francioli infections of the cerebrospinal fluid shunts, B.A. Kaufman and D.G. McLone. Part 4 Central nervous system syndromes mediated by bacterial toxins: botulism, J.M. Hughes tetanus, T.P. Bleck bordetella pertussis and the central nervous system, E.L. Hewlett. Part 5 Spriochetal infections of the central nervous system: central nervous system syphilis, E.W. Hook, III Lyme disease, L. Reik, Jr. Part 6 Fungal infections of the central nervous system: pathogenesis and pathophysiology of fungal infections, J. R. Perfect and D.T. Durack chronic meningitis, T. Tucker and J.J. Ellner diagnosis and treatment of fungal meningitis, J.R. Perfect space-occupying fungal lesions of the central nervous system, K. Sepkowitz and D. Armstrong. Part 7 Protozoal and helminthic infections of the central nervous system: protozoal infections, J.P. Cegielski and D.T. Durack toxoplasmosis, C.S. Dukes et al helminthic infections, M.L. Cameron and D.T. Durack.
728 citations
TL;DR: This review summarizes recent changes in the treatment of adults with community-acquired bacterial meningitis and details the approach to complications such as transtentorial herniation, hydrocephalus, and focal seizures.
Abstract: This review summarizes recent changes in the treatment of adults with community-acquired bacterial meningitis. It explains the initial assessment and management, the use of adjunctive corticosteroids, and intensive care monitoring. The authors detail the approach to complications such as transtentorial herniation, hydrocephalus, and focal seizures.
714 citations
"Viral encephalitis: a clinician’s g..." refers background in this paper
...However, in a patient who is only mildly confused with no focal neurological signs, than a lumbar puncture should be done straight away, without the unnecessary delay of a CT.24 If a CT is going to cause a delay of several hours, then presumptive treatment for both bacterial and/or viral pathogens should be started....
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...puncture should be done straight away, without the unnecessary delay of a CT.(24)...
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...patients, who may lack the clinical signs of an inflammatory mass lesion.(24) Opinions vary as...
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TL;DR: Control of EV71 epidemics through high-level surveillance and public health intervention needs to be maintained and extended throughout the Asia-Pacific region if an effective live-attenuated vaccine is developed.
Abstract: Since its discovery in 1969, enterovirus 71 (EV71) has been recognised as a frequent cause of epidemics of hand-foot-and-mouth disease (HFMD) associated with severe neurological sequelae in a small proportion of cases. There has been a significant increase in EV71 epidemic activity throughout the Asia–Pacific region since 1997. Recent HFMD epidemics in this region have been associated with a severe form of brainstem encephalitis associated with pulmonary oedema and high case-fatality rates. The emergence of large-scale epidemic activity in the Asia–Pacific region has been associated with the circulation of three genetic lineages that appear to be undergoing rapid evolutionary change. Two of these lineages (B3 and B4) have not been described previously and appear to have arisen from an endemic focus in equatorial Asia, which has served as a source of virus for HFMD epidemics in Malaysia, Singapore and Australia. The third lineage (C2) has previously been identified [Brown, B.A. et al. (1999) J. Virol. 73, 9969–9975] and was primarily responsible for the large HFMD epidemic in Taiwan during 1998. As EV71 appears not to be susceptible to newly developed antiviral agents and a vaccine is not currently available, control of EV71 epidemics through high-level surveillance and public health intervention needs to be maintained and extended throughout the Asia–Pacific region. Future research should focus on (1) understanding the molecular genetics of EV71 virulence, (2) identification of the receptor(s) for EV71, (3) development of antiviral agents to ameliorate the severity of neurological disease and (4) vaccine development to control epidemics. Following the successful experience of the poliomyelitis control programme, it may be possible to control EV71 epidemics if an effective live-attenuated vaccine is developed.
672 citations
"Viral encephalitis: a clinician’s g..." refers background in this paper
...Enterovirus 71 has caused massive outbreaks of hand foot and mouth disease in Asia in recent years, which is often associated with aseptic meningitis, encephalitis or myelitis.(7) Nipah virus is a morbillivirus (in the same family as measles) that was recognised for the first time in 1998 when it caused encephalitis in humans in Malaysia....
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