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Background: Patients with suspected encephalitis continue to represent a diagnostic and therapeutic challenge, even in highly resourced centres. In February 2018, we set up a monthly in-person multidisciplinary team meeting (MDT). We describe the experience and outcomes of the MDT over three years., Methods: A retrospective analysis was performed to summarise patient demographics, MDT outcomes and final diagnoses., Results: Over the three-year period, 324 discussions of 238 patients took place. Cases were diverse; approximately 40% related to COVID-19 or brain infection, 40% autoimmune or other inflammatory disorders and 20% encephalitis mimics or uncertain aetiologies. Feedback from an online survey sent to referring teams and attendees highlighted the value of the MDT; 94% reported the discussion was useful and 69% reported resulting change in patient management., Conclusions: Multidisciplinary input is crucial in this challenging area, ensuring that all diagnostic avenues are explored and opening doors to novel diagnostics and therapeutics. It also supports clinicians dealing with unwell patients, including in centres where less specialist input is available, and when decisions have to be made where there is little or no evidence base., Competing Interests: Declaration of Competing Interest MSZ declares honoraria for one lecture each for each of the three mentioned in the last 3 years: Norwegian Neurological Society; Copenhagen Neuropsychological Society, Rigshospitalet; and Cygnet Healthcare. None of the other authors report any conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: As there have been no comprehensive reports of human metapneumovirus-associated encephalopathy (hMPVE), this study examined the clinical features of hMPVE in children in Japan., Method: A nationwide survey of children with hMPVE was conducted using a structured research form. An initial survey asked pediatricians about children with hMPVE treated between 2014 and 2018. A second survey obtained patient information from hospitals that responded to the initial survey and those identified as having treated cases from a literature search. We collected demographic data, symptoms of hMPV infection, neurological symptoms, laboratory data, treatment, and outcomes. Outcomes were determined using the Pediatric Cerebral Performance Category Score., Result: Clinical information was available for 16 children. Their median age was 37 months. Six had preexisting neurological disorders. The interval between the onsets of infection and hMPVE was 4 days. Outcomes were good in 11 patients and poor in 5. There were no significant differences in demographic data, neurological symptoms, or laboratory data between the patients with good and poor outcomes. The encephalopathy subtypes were acute encephalopathy with biphasic seizures and late reduced diffusion in 3, clinically mild encephalitis/encephalopathy with a reversible splenial lesion in 3, hemorrhagic shock and encephalopathy syndrome in 2, and others in 8., Conclusion: The outcomes of children with hMPVE were not very different from those of acute encephalopathy due to other viruses. We found no factors associated with poor outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: Guillain-Barré syndrome (GBS), Fisher syndrome (FS), and Bickerstaff brainstem encephalitis (BBE) are immune-mediated neuropathies presenting with symptoms such as weakness, ophthalmoplegia, ataxia, and consciousness disturbances. Although the epidemiology of GBS and BBE in patients of all ages has been reported, childhood data have not been well-investigated. We aimed to determine the clinical features, therapeutics, and prognoses of childhood GBS, FS, and BBE in Japan., Methods: We sent questionnaires to 1068 pediatric neurologists in Japan from 2014 to 2016 to determine the number of children less than 15 years old with GBS, FS, or BBE and their age and sex. We subsequently performed a secondary survey to investigate the clinical features, laboratory data, treatment, and prognosis., Results: Five-hundred thirty-eight pediatric neurology specialists (50.4%) responded to the first survey. The total number of children with GBS, FS, and BBE in Japan from 2014 to 2016 were 87, 10, and 6, respectively. GBS was classified as acute inflammatory demyelinating neuropathy (35.6%), acute motor axonal neuropathy (20.7%), or acute motor-sensory axonal neuropathy (10.3%), with a male-to-female ratio of 1.29:1.0 and a wide distribution of onset ages. The disease severities of GBS, FS, and BBE were variable, but all children could walk within one year., Conclusion: The prognoses of childhood GBS, FS, and BBE were generally favorable, as long as the patient was promptly treated with either intravenous immunoglobulin or plasma exchange., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Lyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described., Objectives: To describe the available literature on LNB encephalitis and to characterize this patient group through a Scandinavian retrospective cohort study., Data Sources: Medline, Embase, Scopus, Cochrane library., Study Eligibility Criteria: There was no discrimination on study type, time of publication or language., Participants: Review: All articles with definite LNB and confirmed/possible encephalitis., Cohort: LNB cohorts from Denmark, Sweden and Norway 1990-2019 were screened for patients with encephalitis., Methods: Review: Adhering to PRISMA guidelines; two authors extracted reviews and assessed quality of studies., Cohort: Data on demography, symptoms, cerebrospinal fluid findings, differential diagnostic examinations, treatment, residual symptoms, 1-year mortality were registered., Results: Review: 2330 articles screened on title/abstract, 281 full texts, yielding 42 articles (case reports/series or cohort studies), including 45 patients from 18 countries spanning 35 years. Altered mental status ranged from personality changes and confusion to unconsciousness. Common focal symptoms were hemiparesis, ataxia and dysarthria; seven patients had seizures. Median time from symptom onset to hospital was 2 weeks (IQR 2-90 days). Of 38 patients with available follow-up after median 12 months (IQR 5-13), 32 had fully or partially recovered, two had died., Cohort: Thirty-five patients (median age 67 years, IQR 48-76) were included. The encephalitis prevalence was 3.3% (95% CI 2.2-4.4%) among 1019 screened LNB patients. Frequent encephalitis symptoms were confusion, personality changes, aphasia, ataxia. EEGs and neuroimaging showed encephalitis in 93.8% and 20.6%, respectively. Median delay from symptom onset to hospital was 14 days (IQR 7-34), with further 7 days (IQR 3-34) delay until targeted therapy. At follow-up (median 298 days post-treatment; IQR 113-389), 65.6% had residual symptoms. None had died., Conclusions: This study shows that encephalitis is an uncommon, but likely overlooked clinical manifestation of LNB. As the high frequency of residual symptoms may be related to prolonged treatment delay, prompt LNB testing of patients with encephalitis in Borrelia burgdorferi-endemic areas should be considered., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Diverse neuronal antibodies are related to autoimmune encephalitis (AE) and AE-related epilepsy. However, the epidemiological characteristics of AE, AE-associated antibodies, and AE-related seizures are still unclear., Aims: This research evaluated the relationship between AE, AE-related seizures, and neuronal antibodies, as well as the morbidity of AE with early incidence., Methods: The PubMed, Embase, Cochrane, and Web of Science databases were searched. Pooled estimates and 95% confidence intervals (CIs) were calculated using a random-effects model., Results: Of the 4,869 citations identified, 100 articles were reviewed in full, and 42 subgroups were analyzed. The overall incidence of AE patients with seizures was 42% (95% CI: 0.40-0.44), and among them, the incidence of epilepsy in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients was 73% (95% CI: 0.70-0.77). Subsequently, we found that the prevalence of AE as the cause of epilepsy within the pooled period was 1% (95% CI: 0.01-0.02), while the overall positive rate of neuronal antibodies in epilepsy patients was 4% (95% CI: 0.03-0.05). Additionally, the detection rates of different antibodies among epilepsy patients were as follows: anti-NMDAR, 1%; anti-leucine-rich glioma inactivated 1 (LGI1), 1%; anti-contactin-associated protein-like 2 (CASPR2), 2%., Conclusion: Based on our findings, neuronal antibodies may serve as a bridge to study AE and immune-related epilepsy. To further understand the differences in outcomes following different treatment measures, and to provide more information for public health policy and prevention, more research is needed to improve the accuracy of estimations., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To follow prospectively a group of patients with seizures or epilepsy and suggestive clinical features of autoimmune aetiology and find out how many are finally diagnosed with acute symptomatic seizures (ASS) secondary to autoimmune encephalitis or autoimmune-related epilepsy, and how many develop epilepsy., Methods: Consecutive patients meeting the inclusion criteria from 2010 to 2018 were identified. Patients were classified as confirmed, probable autoimmune, non-autoimmune, or unknown., Results: One-hundred and nine patients were included, 64 (48.7 %) women, mean age 55.2 years (SD 17.9). ASS were reported by 61 patients (56 %), while 48 presented epilepsy (44 %). During follow-up 18 patients died (16.5 %). Final diagnosis was autoimmune-relatedepilepsy (confirmed + probable) in 22 cases and ASS secondary to autoimmune encephalitis (confirmed or probable) in 27, non-autoimmune aetiologies or other diagnosis in 49 (44 %), and unknown aetiology in 11 (10.2 %). Neuronal antibodies (ab) were found in 27 patients (24.7 %). T-lymphocyte infiltration in temporal lobes was observed in 2/8 patients (20 %). Neuronal ab were more frequent in the autoimmune groups: 17 patients (29.8 %) vs 1(2.3 %), p:0.001, and they suffered more autoimmune diseases: 37 (75.5 %) vs 12 (24.48 %), p:0.0001, and 34 (69 %) vs 22 (44.9 %) p:0.027, respectively. All patients with GAD ab 17/17 (100 %) evolved to chronic disease. Four patients (29 %) with ASS secondary to autoimmune encephalitis developed epilepsy., Significance: ASS secondary to autoimmune encephalitis or autoimmune-related epilepsy will be diagnosed in nearly half of patients who have been suspected of it. The only diagnostic clue is neuronal ab. Patients who have suffered ASS secondary to autoimmune encephalitis may develop epilepsy over time., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: We previously reported the nationwide, epidemiological data of acute encephalopathy in Japan during 2007-2010. Here we conducted the second national survey of acute encephalopathy during 2014-2017, and compared the results between the two studies to elucidate the trends in the seven years' interval as well as the influence of changes in pediatric viral infections and guidelines for acute encephalopathy in Japan., Methods: The Research Committee on Acute Encephalopathy supported by the Japanese Government sent a questionnaire to 507 hospitals throughout Japan, and collected the responses by mail., Results: A total of 1115 cases from 267 hospitals reportedly had acute encephalopathy during April 2014-June 2017. In this study, the age at onset was younger, the ratios of recently established syndromes, such as acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS), were higher, and the ratio of influenza-associated encephalopathy was lower, than in the previous study. The age at onset of influenza-associated encephalopathy was lower, and that of HHV-6/7-associated encephalopathy higher, compared to the first survey. The outcomes of entire acute encephalopathy remained unchanged., Conclusion: Some of these changes reflected the recent trends of viral infectious diseases including 2009 influenza pandemic, and others the standardization of the diagnosis of acute encephalopathy in Japan., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Acute encephalitis is an important cause of mortality and morbidity in children. We retrospectively identified children (≤15 years of age) admitted with suspected encephalitis at the Intensive Care Unit of the Pediatric Department of Cayenne Hospital between January 2007 and December 2018. A total of 30 children with acute encephalitis were identified. The incidence rate varied from 0 to 10.40 cases/100000 children under 15 years. Proven encephalitis was diagnosed in 73% of patients. Nine cases of acute disseminated encephalomyelitis were diagnosed. The causes of infection (44%) were Haemophilus influenzae, followed by Cryptococcus spp and Varicella Zoster Virus. Four children (13%) died: one case of Streptococcus pneumoniae, one of Haemophilus influenzae, one of Mycobacterium tuberculosis and one with no identified cause. Seventeen percent of children had moderate to severe neurological sequelae. The only factor associated with poor outcome was young age at the time of hospitalization (p = 0.03). Conclusion: This study highlights both vaccine-preventable pathogens and acute disseminated encephalomyelitis as the leading causes of childhood encephalitis in French Guiana., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The aim of this study is to describe demographic data, semiology and etiology in a pediatric population with status epilepticus (SE) and refractory SE (RSE)., Method: We retrospectively reviewed patients with the following inclusion criteria: i) age between two months and eighteen years; ii) SE diagnosis; iii) admission from January 2001 to December 2016; iv) available clinical data., Results: We enrolled 124 patients. Mean and median age was 4.6 ± 4.2 years and 3.3 [1.2-7.5] years respectively. SE had a "de novo" onset in 66.9%. Focal convulsive-SE was the most common semiology (50.8%) whilst generalised (32.3%) and nonconvulsive-SE (NCSE) (16.9%) were less represented. Some etiologies showed a different age distribution: febrile in youngest age (p = 0.002, phi 0.3) and idiopathic-cryptogenic in older children (p = 0.016, phi 0.2). A statistical significance correlation was detected between semiology and etiology (p < 0.001, Cramer's V 0.4), chemotherapy and NCSE (n = 6/21 vs 3/103, p < 0.001) as well as PRES and NCSE (n = 7/21 vs 5/103, p < 0.001). Only 17.7% had a RSE. No correlation was found in demographic and clinical data, but NCSE, acute and idiopathic-cryptogenic etiologies were more frequently associated to RSE. Encephalitis was the most common diagnosis in acute etiologies whereas unknown epilepsy in idiopathic-cryptogenic group., Conclusion: Most of our findings were previously described however we found a significant role of non-antiepileptic treatments (chemotherapy-dialysis) and comorbidity (PRES) determining acute etiology and NCSE. Acute (mostly encephalitis), idiopathic-cryptogenic (mainly unknown-epilepsy) and NCSE were frequently detected in RSE. In the above mentioned conditions a high level of suspicion was recommended., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Introduction: Seasonal influenza-associated neurological complications had high mortality and morbidity rates in recent studies. We reported influenza-associated encephalitis/encephalopathy in children during 2014-2017 in Taiwan, focusing on neurological presentations, neuroimaging correlations, and critical care managements., Materials/subjects: During January 1st 2014 to June 30th 2017, pediatric patients reported to the Taiwan Centers for Disease Control surveillance system for severe complicated influenza infections in the hospital were retrospectively reviewed. Children with influenza-associated encephalitis/encephalopathy were inspected for clinical presentations, laboratory data, neuroimaging studies, treatment modalities, and neurological outcomes., Results: Ten children with median age 5.9 years were enrolled for analysis. Influenza-associated encephalitis/encephalopathy appeared in the spring and summer, with a delayed peak comparing with the occurrence of pneumonia and septic shock. The neurological symptoms developed rapidly within median 1 day after the first fever episode. All patients had consciousness disturbance. Seven patients (70%) had seizures at initial presentation, and six of them had status epilepticus. Anti-viral treatments were applied in all patients, with median door-to-drug time 0.9 h for oseltamivir and 6.0 h for peramivir. Multi-modality treatments also included steroid pulse therapy, immunoglobulin treatment, and target temperature management, with 85.2% of the major treatments administered within 12 h after admission. Nine of the ten patients recovered without neurological sequelae. Only one patient had epilepsy requiring long-term anticonvulsants and concomitant cognitive decline., Conclusions: In highly prevalent area, influenza-associated encephalitis/encephalopathy should be considered irrespective of seasons. Our study suggested the effects of timely surveillance and multi-modality treatments in influenza-associated encephalitis/encephalopathy., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Women appear to be more vulnerable to the depressogenic effects of inflammation than men. Chronic stress, one of the most pertinent risk factors of depression and anxiety, is known to induce behavioral and affective-like deficits via neuroimmune alterations including activation of the brain's immune cells, pro-inflammatory cytokine expression, and subsequent changes in neurotransmission and synaptic plasticity within stress-related neural circuitry. Despite well-established sexual dimorphisms in the stress response, immunity, and prevalence of stress-linked psychiatric illnesses, much of current research investigating the neuroimmune impact of stress remains exclusively focused on male subjects. We summarize and evaluate here the available data regarding sex differences in the neuro-immune consequences of stress, and some of the physiological factors contributing to these differences. Furthermore, we discuss the extent to which sex differences in stress-related neuroinflammation can account for the overall female bias in stress-linked psychiatric disorders including major depressive disorder and anxiety disorders. The currently available evidence from rodent studies does not unequivocally support the peripheral inflammatory changes seen in women following stress. Replication of many recent findings in stress-related neuroinflammation in female subjects is necessary in order to build a framework in which we can assess the extent to which sex differences in stress-related inflammation contribute to the overall female bias in stress-related affective disorders., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Primary human immunodeficiency virus (HIV) neuropathologies can affect all levels of the neuraxis and occur in all stages of natural history disease. Some, like HIV encephalitis, HIV myelitis, and diffuse infiltrative lymphocytosis of peripheral nerve, reflect productive infection of the nervous system; others, like vacuolar myelopathy, distal symmetric polyneuropathy, and central and peripheral nervous system demyelination, are not clearly related to regional viral replication, and reflect more complex cascades of dysregulated host immunity and metabolic dysfunction. In pediatric patients, the spectrum of neuropathology is altered by the impacts of HIV on a developing nervous system, with microcephaly, abundant brain mineralization, and corticospinal tract degeneration as examples of this unique interaction. With efficacious therapies, CD8 T-cell encephalitis is emerging as a significant entity; often this is clinically recognized as immune reconstitution inflammatory syndrome, but has also been described in the context of viral escape and treatment interruption. The relationship of HIV neuropathology to clinical symptoms is sometimes straightforward, and sometimes mysterious, as individuals can manifest significant deficits in the absence of discrete lesions. However, at all stages of the natural history disease, neuroinflammation is abundant, and critical to the generation of clinical abnormality. Neuropathologic and neurobiologic investigations will be central to understanding HIV nervous system disorders in the era of efficacious therapies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Human immunodeficiency virus (HIV)-infected individuals are particularly susceptible to several central nervous system infections: human cytomegalovirus, which may cause encephalitis, ventriculitis, polyradiculitis, or polyradiculomyelitis; Mycobacterium tuberculosis, which can cause meningitis or space-occupying lesions; and Treponema pallidum subspecies pallidum (T. pallidum), which affects the meninges, cerebrospinal fluid, cranial nerves, and vasculature in early neurosyphilis, and additionally the brain and spinal cord parenchyma in late neurosyphilis. Central nervous system cytomegalovirus infection is seen in HIV-infected individuals with very advanced immunosuppression. Its prognosis is poor and optimal therapy has not been determined. Tuberculous meningitis has a high mortality in those also infected with HIV, especially in the developing world, and better therapies are urgently needed. As the rates of syphilis increase in the developed world, neurosyphilis and in particular ocular syphilis are increasingly reported. The likelihood of all three of these central nervous system infections is decreased in individuals who receive potent antiretroviral therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Guillain-Barré syndrome (GBS), Miller Fisher syndrome (MFS), and Bickerstaff brainstem encephalitis (BBE) are usually monophasic, but some patients experience recurrences after long asymptomatic intervals. We aimed to investigate clinical features of recurrent GBS, MFS, and BBE at a single hospital., Methods: Records from 97 consecutive patients with GBS, MFS or BBE who were admitted to a tertiary hospital between 2001 and 2013 were reviewed. Clinical and laboratory features of patients with recurrent GBS, MFS, or BBE were investigated., Results: Patients included 55 (32 males) with GBS, 34 (22 males) with MFS, and 8 (6 males) with BBE. Recurrent cases occurred in 2 (4%) of the 55 patients with GBS, 4 (12%) of the 34 patients with MFS, and 2 (25%) of the 8 patients with BBE. Patients with recurrent MFS had a tendency to be younger at the first episode than patients with non-recurrent MFS (median, 22 versus 37years old). Symptoms and signs were less severe during relapses than during the initial episode in recurrent patients., Conclusions: Recurrences occurred more frequently in patients with MFS or BBE compared with those with GBS. Patients with recurrent MFS might be younger than those with non-recurrent MFS., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Adult mosquitoes rely on ingestion of sugar from plants to survive, swarm and mate. Culex pipiens pallens Coguillett is the primary vector of lymphatic filariasis and epidemic encephalitis. Little is known about the effect of feeding on different sugar sources on the survivorship and fecundity of Cx. pipiens pallens. In the present study, newly emerged mosquitoes were exposed to several flowering plant and seed pod species with different olfactory preferences, and the survival times of mosquitoes exposed to these sugar sources were determined. The proportions of mosquitoes that ingested sugar from host plants were investigated by cold anthrone tests. The numbers of eggs per egg raft laid by mosquitoes were compared when they were provided with different sugar sources and one blood meal. The results revealed that feeding on different kinds of sugar sources significantly affected female and male mosquitoes' survival times. Cold anthrone tests indicated that the proportions of sugar-positive mosquitoes from different nutritional regimes within 24h corresponded to the preference rankings of Cx. pipiens pallens to these sugar sources, and rapid declines in the proportions of surviving individuals might be attributed to their insufficient ingestion of sugar from nutritional regimes. Feeding on different sugar sources strongly affected the proportions of engorged mosquitoes, and females that had fed on their preferred sugar sources laid more eggs than mosquitoes provided with less preferred sugar sources. The results would provide insights in developing mosquito control strategies that target the sugar feeding behavior of mosquitoes., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Hashimoto's encephalopathy (HE) is a rare syndrome of progressive or relapsing-remitting encephalopathy associated with elevated serum anti-thyroid antibody concentrations. It is thought to be an autoimmune process that generally responds well to high-dose corticosteroids and other immunomodulatory therapies. However, some patients are unresponsive to steroids or are unable to receive immune therapy. A viable alternative is needed for this group. Given that seizure and EEG abnormalities are commonly associated with this syndrome, we postulate that treatment with levetiracetam, which has duel anti-inflammatory and anti-seizure mechanisms, might show clinical benefit. We present the cases of two patients who met the criteria for HE but were unable to receive steroids due to labile diabetes. They were both successfully treated with levetiracetam., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Enterovirus (HEV) and parechovirus (HPeV) infections are common in the neonatal period, and account for a large portion of febrile illnesses during the summer season. HEV infections appear clinically and seasonally similar to HPeV infections. In this study, we present the virological and clinical data from neonates infected with HEV or HPeV and hospitalized in a neonatal intensive care unit for sepsis-like illness or neurologic disorders. In the period January 2010 to October 2013, 54 cerebrospinal fluid (CSF) and 10 plasma samples were obtained from 60 newborns aged <30 days. A total of 7/60 (11.6%) patients were positive for HEV infection and 3 (5.0%) were positive for HPeV infection as determined by specific real-time RT-PCR. The most common clinical signs were fever, irritability, hyporeactivity and, in a few cases, rash. All infections were observed during the summer-fall period. In conclusion, HEV and HPeV were shown to account for a significant portion of febrile illnesses in neonates requiring hospitalization., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Acute encephalitis syndrome (AES) is a constellation of symptoms that includes fever and altered mental status. Most cases are attributed to viral encephalitis (VE), occurring either in outbreaks or sporadically. We conducted hospital-based surveillance for sporadic adult-AES in rural Central India in order to describe its incidence, spatial and temporal distribution, clinical profile, etiology and predictors of mortality., Methods: All consecutive hospital admissions during the study period were screened to identify adult-AES cases and were followed until 30-days of hospitalization. We estimated incidence by administrative sub-division of residence and described the temporal distribution of cases. We performed viral diagnostic studies on cerebrospinal fluid (CSF) samples to determine the etiology of AES. The diagnostic tests included RT-PCR (for enteroviruses, HSV 1 and 2), conventional PCR (for flaviviruses), CSF IgM capture ELISA (for Japanese encephalitis virus, dengue, West Nile virus, Varicella zoster virus, measles, and mumps). We compared demographic and clinical variables across etiologic subtypes and estimated predictors of 30-day mortality., Results: A total of 183 AES cases were identified between January and October 2007, representing 2.38% of all admissions. The incidence of adult AES in the administrative subdivisions closest to the hospital was 16 per 100,000. Of the 183 cases, a non-viral etiology was confirmed in 31 (16.9%) and the remaining 152 were considered as VE suspects. Of the VE suspects, we could confirm a viral etiology in 31 cases: 17 (11.2%) enterovirus; 8 (5.2%) flavivirus; 3 (1.9%) Varicella zoster; 1 (0.6%) herpesvirus; and 2 (1.3%) mixed etiology); the etiology remained unknown in remaining 121 (79.6%) cases. 53 (36%) of the AES patients died; the case fatality proportion was similar in patients with a confirmed and unknown viral etiology (45.1 and 33.6% respectively). A requirement for assisted ventilation significantly increased mortality (HR 2.14 (95% CI 1.0-4.77)), while a high Glasgow coma score (HR 0.76 (95% CI 0.69-0.83)), and longer duration of hospitalization (HR 0.88 (95% CI 0.83-0.94)) were protective., Conclusion: This study is the first description of the etiology of adult-AES in India, and provides a framework for future surveillance programs in India., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Purpose: Two hundred and fifty-three patients were included in a study on the etiology of encephalitis, carried out in France in 2007. Tuberculosis was the second most frequently identified cause, after HSV and with the same number of cases as VZV. The authors report the specific features of patients presenting with tuberculosis encephalitis (TE)., Methods: TE patients were defined as patients presenting with encephalitis, with positive culture or PCR for Mycobacterium tuberculosis, or the association of clinical, biological, imaging, and epidemiological evidence (possible cases). Clinical, microbiological, and brain imaging data was analyzed and compared to that of other included patients., Results: Twenty cases of TE were identified. The M/F sex-ratio was 1.5, the mean age 53 years. Four (20%) patients had a history of tuberculosis before the encephalitis. The median delay between the onset of general and neurological symptoms was significantly longer for tuberculosis cases than for others (10 days vs. 2; P<10(-10)). The median CSF protein level was significantly higher for tuberculosis cases (2.1 g/L vs. 0.8 g/L, P=0.002). CT scan and MRI were normal on admission for eight patients out of 17. Fourteen isolated strains of M. tuberculosis were susceptible to first-line anti-tuberculosis drugs and one was rifampicin-resistant. Six (33%) patients died during hospitalization and two were lost to follow-up. Ten out of 12 (78.6%) had persisting neurological symptoms on discharge., Discussion: Despite non-multiresistant MT strains, the case fatality rate among TE patients was high in our series. Early brain imaging is poor contributive for the diagnosis of TE., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Alzheimer's disease (AD) involves progressive neurodegeneration in the presence of misfolded proteins and poorly-understood inflammatory changes. However, research has shown that AD is genetically, clinically, and pathologically heterogeneous. In frozen brain samples of frontal cortex (diseased) and cerebellum (nondiseased) from the University of Kentucky Alzheimer's Disease Center autopsy cohort, we performed gene expression analysis for genes categorizing inflammatory states (termed M1 and M2) from early and late stage AD, and age-matched nondemented controls. We performed analysis of the serum samples for a profile of inflammatory proteins and examined the neuropathologic data on these samples. Striking heterogeneity was found in early AD. Specifically, early-stage AD brain samples indicated apparent polarization toward either the M1 or M2 brain inflammatory states when compared with age-matched nondisease control tissue. This polarization was observed in the frontal cortex and not in cerebellar tissue. We were able to detect differences in AD neuropathology, and changes in serum proteins that distinguished the individuals with apparent M1 versus M2 brain inflammatory polarization., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A research committee supported by the Japanese government conducted a nationwide survey on the epidemiology of acute encephalopathy in Japan using a questionnaire. A total of 983 cases reportedly had acute encephalopathy during the past 3 years, 2007-2010. Among the pathogens of the preceding infection, influenza virus was the most common, followed by human herpesvirus-6 (HHV-6) and rotavirus. Among syndromes of acute encephalopathy, acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was the most frequent, followed by clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS), acute necrotizing encephalopathy (ANE) and hemorrhagic shock and encephalopathy syndrome (HSES). Influenza virus was strongly associated with ANE and MERS, HHV-6 with AESD, and rotavirus with MERS. Mortality was high in ANE and HSES, but was low in AESD, MERS and HHV-6-associated encephalopathy. Neurologic sequelae were common in AESD and ANE, but were absent in MERS., (Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objectives: To detect the presence of Toscana virus (TOSV) circulation in Tunisia and to study its role in viral meningo-encephalitis., Patients and Methods: A total of 315 (167 sera and 178 cerobrospinal fluid [CSF]) samples was investigated. These samples are colleted from Tunisian patients with neurological diseases during the period between January 2003 and December 2009. All samples were tested negative for enterovirus, Herpes Simplex virus and West Nile virus. Detection for IgM and IgG specific to TOSV was done by ELISA tests., Results: Specific IgM for TOSV were detected in 10 % of patients with neurological diseases (31 cases). These recent infections were distributed throughout the study period and predominated during summer and automn. Patients were originated, in the majority from the coastal region. IgG were isolated in 22 cases (7 %) corresponding to previous infection., Conclusion: This is the first report of TOSV circulating in Tunisia and its frequent implication in neurological diseases. These results incited to include TOSV as one of the viral etiologies to target in the diagnosis of viral meningitis and encephalitis in the country., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Purpose: The authors had for aim to describe the characteristics of listeriosis encephalitis patients enrolled in a national study., Methods: Listeria monocytogenes was identified as the forth etiology of encephalitis, in a prospective study in France, in 2007. We analyzed 12 cases with confirmed listeriosis (seven with rhombencephalitis, five with encephalitis) and compared them with encephalitis of other etiologies and with listeriosis encephalitis, mandatorily notified during the same year., Results: L. monocytogenes strains were genoserotyped as IVb (n=6), IIa (n=3), and IIb (n=3). Cerebrospinal fluid (CSF) median protein level was 2.5g/L and the median WBC counts was 367cells/mm(3). Among twelve patients, seven patients had ongoing comorbidities. The case fatality rate during hospitalization was 50%. Patients presenting with listeriosis enrolled in the study did not differ from those reported to the mandatory surveillance system according to their demographical characteristics and comorbidities. They were older, presented more frequently with cancer, or were more often under corticosteroid treatment than patients presenting with encephalitis due to other etiologies., Conclusions: Neurolisteriosis has a poor prognosis, thus it should be considered early in patients presenting with encephalitis to improve its management., (Copyright © 2011. Published by Elsevier SAS.)

Chronic systemic inflammatory conditions, such as atherosclerosis, diabetes and obesity are associated with increased risk of stroke, which suggests that systemic inflammation may contribute to the development of stroke in humans. The hypothesis that systemic inflammation may induce brain pathology can be tested in animals, and this was the key objective of the present study. First, we assessed inflammatory changes in the brain in rodent models of chronic, systemic inflammation. PET imaging revealed increased microglia activation in the brain of JCR-LA (corpulent) rats, which develop atherosclerosis and obesity, compared to the control lean strain. Immunostaining against Iba1 confirmed reactive microgliosis in these animals. An atherogenic diet in apolipoprotein E knock-out (ApoE(-/-)) mice induced microglial activation in the brain parenchyma within 8 weeks and increased expression of vascular adhesion molecules. Focal lipid deposition and neuroinflammation in periventricular and cortical areas and profound recruitment of activated myeloid phagocytes, T cells and granulocytes into the choroid plexus were also observed. In a small, preliminary study, patients at risk of stroke (multiple risk factors for stroke, with chronically elevated C-reactive protein, but negative MRI for brain pathology) exhibited increased inflammation in the brain, as indicated by PET imaging. These findings show that brain inflammation occurs in animals, and tentatively in humans, harbouring risk factors for stroke associated with elevated systemic inflammation. Thus a "primed" inflammatory environment in the brain may exist in individuals at risk of stroke and this can be adequately recapitulated in appropriate co-morbid animal models., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Encephalitis is caused by a variety of conditions, including infections of the brain by a wide range of pathogens. A substantial number of cases of encephalitis defy all attempts at identifying a specific cause. Little is known about the long-term prognosis in patients with encephalitis of unknown aetiology, which complicates their management during the acute illness. To learn more about the prognosis of patients with encephalitis of unknown aetiology, patients in whom no aetiology could be identified were examined in a large, single-centre encephalitis cohort. In addition to analysing the clinical data of the acute illness, surviving patients were assessed by telephone interview a minimum of 2 years after the acute illness by applying a standardized test battery. Of the patients with encephalitis who qualified for inclusion (n = 203), 39 patients (19.2%) had encephalitis of unknown aetiology. The case fatality in these patients was 12.8%. Among the survivors, 53% suffered from various neurological sequelae, most often attention and sensory deficits. Among the features at presentation that were associated with adverse outcome were older age, increased C-reactive protein, coma and a high percentage of polymorphonuclear cells in the cerebrospinal fluid. In conclusion, the outcome in an unselected cohort of patients with encephalitis of unknown aetiology was marked by substantial case fatality and by long-term neurological deficits in approximately one-half of the surviving patients. Certain features on admission predicted an unfavourable outcome., (© 2010 The Authors. Journal Compilation © 2010 European Society of Clinical Microbiology and Infectious Diseases.)

Purpose: Rasmussen's encephalitis (RE) is a progressive and catastrophic epileptic disorder caused by chronic localized encephalitis. We performed a nationwide survey of RE to assess the clinical picture, treatment effect, and prognosis of Japanese RE patients., Subjects & Methods: The subjects were 27 patients (male:12; female:15) from 13 medical facilities. All of them satisfied the clinical and neuroimaging criteria for RE, including 14 pathologically proven cases., Results: They were divided into the childhood-onset rapidly progressive type (CORP, n=19), and late-onset slowly progressive type (LOSP, n=8). The mean age at epilepsy onset was 4 years and 4 months in CORP, and 16 years in LOSP. The mean period between the onset age of epilepsy and development of frequent seizures was 1 year and 4 months in the former, and 3 years and 4 months in the latter. The immunomodulatory treatment including high-dose steroid (n=14) and high-dose intravenous immunoglobulin therapies (IVIgG, n=12) achieved more than a 50% reduction in the seizure frequency in 5 (36%) and 4 (33%) patients, respectively. Eight and seven patients underwent focal cortical resection and functional hemispherectomy, leading to significant improvement in 5 of the 8 patients and excellent seizure control in all 7 patients, respectively., Conclusion: Although the high-dose steroid and IVIG therapies may have alleviated the exacerbation of seizures in those with RE, they could not halt the disease progression. Functional hemispherectomy is still the only curative therapy for RE, despite the fact that the early introduction of this procedure remains controversial., (Copyright (c) 2009 Elsevier B.V. All rights reserved.)

Objective: To analyse the underlying causes, therapeutic response and outcomes of convulsive refractory status epilepticus (RSE)., Methodology: This retrospective analysis was carried on 98 patients with RSE (age: 16.9+/-14.5 years). All had received a combination of parenteral benzodiazepine and phenytoin or phenobarbitone followed by other anti-epileptic drugs (AEDs). The clinical, EEG, imaging features of convulsive RSE and long-term seizure outcome were analysed., Results: Seventy six patients had de novo RSE for the first time in life. The mean duration of RSE, before and during NICU admission was 3.4+/-3.2 days and 2.9+/-2.4 days respectively. The mean duration of NICU stay and mechanical ventilation was 17.4+/-14.5 was 14.4+/-12.8 days respectively. The precipitating factors included viral fever - 13, AEDs stoppage - 7 and alcohol - 1. EEG was abnormal in 81.5% of patients. CT and MRI were abnormal in 63.4% and 82.3% respectively. Thirty-four patients died and compared to those surviving, patients were older, had lesser duration of NICU stay and elevated CSF protein. Dependence for activities of daily living (ADL) at discharge was: recovered - 29, mild to moderate - 13 and severe - 22. Seizure outcome in 64 patients after 43.5+/-58.2 weeks were - seizure-free: 65.6%, one seizure: 21.8%, >1 seizure/month: 14.1%, and seizure recurrence requiring admission: 1.5%. After six and twelve months of follow up, the long-term seizure outcome were: seizure-free: 48.3% and 28.6%; one seizure: 27.6% and 38.1%; >1 seizure/month: 20.7% and 28.6%; and seizure recurrence requiring admission: 3.4% and 4.7% respectively. Among those survived 49 de novo RSE, about one-third developed post-SE symptomatic seizures after 30.1+/-54.4 weeks., Conclusions: Seizures could still be controlled in two-thirds of patients with convulsive RSE. About 30% of patients achieved long-term seizure freedom.

Anti-NMDA-receptor encephalitis has been described only recently among other causes of paraneoplastic and auto-immune limbic encephalitis. Its frequency is probably underestimated. The very characteristic clinical presentation, the severity of symptoms frequently leading to the intensive care unit, the therapeutic implications of the diagnosis whatever the cause, paraneoplastic or not and, once treated, the possibility of a full recovery or mild sequels in the majority of cases justify a surveillance either in neurology wards or in infectious, psychiatric, intensive care, or pediatric units. The authors review the history of this disease, the available epidemiological data, the characteristic clinical presentation of patients, the differential diagnosis, and the suggested treatment according to an up-to-date literature review.

Acute encephalitis with refractory, repetitive partial seizures (AERRPS) represents a peculiar form of encephalitis mainly affecting children. They usually present abruptly with seizure or impaired consciousness as well as high-grade fever following antecedent infection. Seizures in AERRPS are almost exclusively of localized origin, whose semiology includes eye deviation, hemifacial twitching, hemiclonic convulsion, and autonomic manifestations. Partial seizures are brief, but repeat with increasing frequency and develop status epilepticus at nadir. They are extremely pharmaco-resistant and are only suppressed by intravenous administration of high-dose barbiturates. Although acute seizures are hardly controlled, patients gradually recover with decreasing seizure frequency and continuously evolve into post-encephalitic epilepsy without latent period. Residual cognitive impairment is common. Electroencephalograms in active stage demonstrate electrical seizure activities and interictal periodic discharges. Magnetic resonance imaging reveals late cerebral atrophy with limited signal abnormality. Persistent fever during active stage, cerebrospinal fluid (CSF) pleocytosis, and up-regulation of neopterin raise the hypothesis that inflammatory process is involved in this condition. Furthermore, early production of autoantibody against NMDA receptor 2B in serum and CSF, although its disease specificity is still in controversy, is suggestive of autoimmune etiology. Exploration for definite clinical marker is currently in progress.

Background: Acute febrile encephalopathy (AFE) is a common cause of childhood hospital admissions in Lucknow. In recent years, many patients have been hospitalized with AFE and hemorrhagic manifestations, some of whom were proven to have dengue viral infection., Objectives: To (i) define the role of dengue encephalopathy (DE) as a cause of AFE in children in Lucknow, (ii) document features of dengue hemorrhagic fever (DHF) in them and (iii)compare clinical features of definite dengue and non dengue AFE., Study Design: Prospective study at a teaching hospital in northern India. Children between 1-12 years of age hospitalized with fever and altered consciousness of 2 weeks or less duration were enrolled after excluding bacterial and tuberculous meningitis and frank hepatic encephalopathy. Clinical and laboratory details were charted. Haemagglutination inhibition (HI) test for dengue and Japanese encephalitis viruses in paired sera and IgM antibody capture ELISA for dengue were done. Real time PCR was done in those samples testing positive for dengue IgM. Those with either positive HI test or positive dengue PCR in CSF or serum were considered definite dengue infection and features of DHF were charted in them. Those negative for IgM antibodies after 5 days of illness or whenever done, HI test, were considered definite non dengue. Clinical and laboratory features were compared between definite dengue and non dengue groups., Results: A total of 265 patients of AFE were enrolled over a 2 year period. HI test was positive in 15/49 (30.6%) and IgM in 52/238 (21.8%) patients thus tested. A total of 62 patients were positive for dengue antibodies by either test. Real time PCR assay for dengue virus genome was positive in 28/42 (69%) tested -- 21/29 (72.4%) in CSF and 9/15 (60%) in serum. A total of 39 patients met the criteria for definite dengue infection of which only 2 fulfilled the WHO criteria for DHF. Comparing DE and non DE, rash, bleeding, swelling over body, and hepatomegaly were significantly more common and meningeal signs less frequent in DE. Mean platelet counts and serum albumen were lower and liver enzymes and INR were significantly higher in DE., Conclusions: Dengue viral infection is a cause of AFE in children in this region. Majority of DE here appears to be due to viral invasion of brain as suggested by high PCR positivity in CSF and lack of WHO criteria for DHF. Differentiating features of DE include swelling and hepatic dysfunction.

The neurological and psychiatric manifestations of Borrelia burgdorferi sensu lato are so numerous that Borrelia is also called the "new great imitator". Thus knowing about the multiple clinical aspects of neuroborreliosis is necessary for the clinician. We reviewed literature for "classical" neuroborreliosis such as acute meningoradiculitis or chronicle encephalomyelitis, but also for encephalitis, myelitis, polyneuritis, radiculitis and more controversial disorders such as chronic neurological disorders, ischemic and hemorrhagic stroke, and motor neuron disease. We specified every time on which basis each disorder was attributed to Lyme disease, particularly if European or American criteria were met. Every part of the nervous system can be involved: from central to peripheral nervous system, and even muscles. In endemic areas, Lyme serology must be assessed in case of unexplained neurological or psychiatric disorder. In case of positive serology, CSF assessment with intrathecal anti-Borrelia antibody index will be more efficient to prove the diagnosis.

Many virus and bacteria can cause encephalitis but are rarely identified as the aetiological agent by individual diagnosis. In France, the only continuous source of information about encephalitis is the national hospital medical database (NHMD). Data from the VIH-negative patients recorded in mainland France between 2000 and 2002 with a diagnosis of encephalitis were extracted and analysed according to demographic, geographical and temporal distribution. Hospitalisation details were described. An average of 1200 patients was recorded each year. They were residents of all French districts and equally hospitalized in university hospitals and non university hospitals. Their mean age was 38, and most were men. The aetiological diagnosis was unknown for 80%. The most frequent aetiological diagnosis was herpes simplex virus in adults, and VZV virus in children. These results give us some clues to design a national study on encephalitis. The study will be implemented in mainland France in 2007 and will last one year. We invite all voluntary hospitals to include their encephalitic patients in our study.

Systemic inflammatory response syndrome (SIRS) is a medical condition in which the all-organ microcirculation is affected including nervous system. We describe neurological findings in 64 patients with SIRS at Hospital das Clínicas of Sao Paulo University School of Medicine; 45.3% were male and 54.7% female; their age ranged from 16 to 95 years old. SIRS was caused by infection in 68.8% of patients, trauma in 10.9%, burns in 7.8%, and elective surgery in 4.7%. The central nervous system involvement occurred in 56.3% of patients and was characterized as encephalopathy in 75%, seizures in 13.9%, non-epileptic myoclonus in 2.8%, and ischemic stroke in 8.3%. The magnetic resonance imaging, cerebrospinal fluid and electroencephalographic changes were unremarkable in encephalopathic patients. Neuromuscular disorders were diagnosed in 43.7%. Critical ill polyneuropathy was characterized in 57.1%, critical ill myopathy in 32.1%, demyelinating neuropathy in 7.2%, and pure motor neuropathy in 3.6%. Nerve and muscle pathological studies dismissed inflammatory abnormalities. The identification of these conditions has important economic implications and may change the critically ill patients' prognosis.

Objectives: This retrospective study was carried out to determine the prevalence of cerebromeningeal diseases at the Fann Teaching Hospital Infectious Diseases Clinic, in Dakar, and to describe their epidemiological, clinical, and etiological features., Patients and Methods: Data was collected for analysis from patients files recorded from January 1, 2001 to December 31, 2003., Results: Four hundred seventy cases were identified (11.4% of total admissions) with a M/F sex ratio of 1.38 and a mean age of 33 years. Eighty-nine patients were infected by HIV and clinical presentations included fever (78%), meningeal syndrome (57.4%), coma (64.9%), convulsions (19%), focal neurological deficits (15.5%), and cranial nerves dysfunction (7.2%). Etiologies presented as cerebral malaria (85 cases), purulent meningitis (51 cases), neuromeningeal cryptococcosis (37 cases), tuberculous meningitis (11 cases), intracranial abscess (10 cases), toxoplasma encephalitis (4 cases), cerebrovascular attack (11 cases), and cerebromeningeal hemorrhages (3 cases). In as many as 248 cases (52.8%) no etiology could be found. The case fatality rate was 44.5% overall (209 deaths) and 68.5% among HIV-infected patients. Neurological sequels were found in 22 survivors (8.8%), consisting in focal neurological deficit (12 cases), deafness (5 cases), diplopia (2 cases), dementia (2 cases), postmeningitic encephalitis (1 case)., Conclusion: These results show the need to improve our technical capacities in our diagnostic laboratories, the prevention of opportunistic infections in the course of HIV/AIDS infection, and the involvement of various specialists in the management of cerebromeningeal diseases.

Epidemiologic observations support the contention that infection, inflammation, and neonatal white matter damage (WMD) are associated. We also have documentation from multiple experimental models that infection/inflammation can damage developing white matter. Based on these observations in humans and animals, we offer causal inferences using widely accepted causal criteria and the multivariable model of causation. As much as we want to, however, we are reluctant to state unequivocally that inflammation causes WMD in humans born much before term. The main reason is that we lack convincing evidence that inflammation precedes WMD (temporal evidence). We also need more (and more detailed) observational studies clarifying the presumed infection --> inflammation --> WMD sequence before we can initiate intervention trials to reduce the risk of WMD.

Melioidosis, which is infection with the gram-negative bacterium Burkholderia pseudomallei, is an important cause of sepsis in east Asia and northern Australia. In northeastern Thailand, melioidosis accounts for 20% of all community-acquired septicaemias, and causes death in 40% of treated patients. B pseudomallei is an environmental saprophyte found in wet soils. It mostly infects adults with an underlying predisposing condition, mainly diabetes mellitus. Melioidosis is characterised by formation of abscesses, especially in the lungs, liver, spleen, skeletal muscle, and prostate. In a third of paediatric cases in southeast Asia, the disease presents as parotid abscess. In northern Australia, 4% of patients present with brain stem encephalitis. Ceftazidime is the treatment of choice for severe melioidosis, but response to high dose parenteral treatment is slow (median time to abatement of fever 9 days). Maintenance antibiotic treatment is with a four-drug regimen of chloramphenicol, doxycycline, and trimethoprim-sulfamethoxazole, or with amoxicillin-clavulanate in children and pregnant women. However, even with 20 weeks' antibiotic treatment, 10% of patients relapse. With improvements in health care and diagnostic microbiology in endemic areas of Asia, and increased travel, melioidosis will probably be recognised increasingly during the next decade.

We studied all the adult patients with acute encephalitis, 322 in all, in the Helsinki area, Finland, during the years 1967--1991. The average incidence was 1.4/100000 adults/year. The proportion of known and suggested etiologies in 5-year periods has risen from 36 (1967--71) to 59% (1987--91). Herpes simplex virus was identified most often (16%), followed by varicella-zoster (5%), mumps (4%), and influenza A viruses (4%). In addition, 20 other agents were identified. The leading cause of encephalitis in patients aged 65 years or more was varicella-zoster virus. Eighteen patients (5.6%) died. It appears that the etiology of encephalitis changes with age and with time. It is important to establish the etiological pattern, as this assists in prompt diagnosis, which is a prerequisite for successful therapy.

Background: Following the 1996 discovery of a rabies-like lyssavirus in Australian flying foxes, it was unclear whether this was a new epizootic or an unrecognised, previously existing disease., Objective: To review cases of unexplained encephalitis in the Northern Territory (NT) to test available clinical specimens for lyssavirus and survey the use of diagnostic tests by clinicians., Methods: The NT hospital morbidity database was searched from January 1992 to September 1996 for all Royal Darwin Hospital (RDH) cases with an ICD-9 code encompassing encephalitis or viral meningitis. Final diagnoses were determined by hospital record review. For cases of unexplained encephalitis, we assessed the use of diagnostic tests and located clinical specimens for testing for lyssavirus-specific inclusion bodies via immunohistochemistry, immunofluorescence and reverse-transcriptase polymerase chain reaction (RT-PCR)., Results: Encephalitis occurred in 34/154 (22%) cases located by the search; 53% (18/34) of encephalitis cases were unexplained. Of these, 24% had no serology performed and 47% had no blood cultures taken. Four (22%) died and two had autopsies. These were the only two cases with clinical specimens available for testing. They were negative for lyssavirus. None of the 71 cases coded as viral meningitis had unexplained encephalitis., Conclusion: There was a considerable proportion of unexplained illness among NT cases of encephalitis., Implications: Clinicians should test for lyssavirus in patients with encephalitic symptoms and a postmortem should be sought where death is unexplained. Specimens should be stored to enable testing for emerging infectious diseases.

For over a decade we have maintained within a district of 5 million people, a system of prompt reporting of cases of childhood vaccine-preventable diseases, encephalitis, meningitis, hepatitis, and rabies; together with a sentinel laboratory surveillance of cholera, typhoid fever, malaria, HIV infection and antimicrobial-resistance patterns of selected pathogens. The system combined government and private sectors, with every hospital enrolled and participating. Reports were scanned daily on a computer for any clustering of cases. Interventions included investigations, immunisation, antimicrobial treatment, health education, and physical rehabilitation of children with paralysis. All vaccine-preventable diseases have declined markedly, whilst malaria and HIV infections have increased steadily. Annual expense was less than one US cent per head. The reasons for the success and sustainability of this model include simplicity or reporting procedure, low budget, private-sector participation, personal rapport with people in the network, regular feedback of information through a monthly bulletin, and the visible interventions consequent upon reporting. This district-level disease surveillance model is replicable in developing countries for evaluating polio eradication efforts, monitoring immunisation programmes, detecting outbreaks of old or new diseases, and for evaluating control measures.

Putative etiology was studied in 991 patients with symptomatic localization-related epilepsies seen in a university hospital in South India. They formed 39% of patients with various types of epilepsies and epileptic syndromes seen during the study period. Seizure occurred in close temporal association with an acute central nervous system (CNS) insult in 53% of patients. Infections of CNS including single CT enhancing lesion (SCTEL) accounted for 77% of patients with acute symptomatic epilepsy. Cerebrovascular diseases were the risk factors in 48% of patients with remote symptomatic epilepsy. Neurocysticercosis, SCTEL and small single cerebral calcific CT lesion (SSCCCTL) together accounted for 40% of etiological factors and neurotuberculosis for 10%. Infections of the central nervous system and SCTEL together were the putative risk factors in 52% of patients aged < or =40 years. Cerebrovascular diseases were the etiological factors in 64% of patients aged >40 years. Neurological handicaps from birth manifested by mental retardation and/or cerebral palsy was the feature in 21% of children. The type of seizure was either simple partial or complex partial with or without secondary generalization in 76% of patients. The remaining patients presented with either generalized tonic clonic seizures or unlocalized seizures. Localization to a single site of seizure origin proposed by the International League Against Epilepsy (ILAE) was possible in only 67.5% of patients. The most readily identifiable was motor cortex. In patients with unlocalized or generalized seizures the type of pathology was diffuse in 17% of patients and in 48.5% of patients, the lesion was located in the frontal brontoparietal lobe.

The case records for 256 patients with acute encephalitis, including meningoencephalitis, acute encephalopathy and Reye syndrome, were obtained from 36 departments of pediatrics in large hospitals through questionnaires which were sent in 1990-92. The incidence rate per 100,000 child years was 3.3, and was more frequent in children aged 0-4 years (rate 6.6) than 5-15 years (rate 2.0), with statistical significance. The disease in the 105 etiologically diagnosed patients was due to measles virus (24), herpes simplex (21), rubella (24), and other agents (36), including two cases of human herpesvirus 6. A third of the infants with measles encephalitis were first seen at less than 18 months of age. Eighteen cases of rubella encephalitis occurred during an epidemic of rubella in Aichi Prefecture, 1987-88. The short-term outcome (mean length of follow-up: 2 years 3 months) of encephalitis was death in 20 cases (7.8%) and sequelae in 58 (24%). Eleven patients died within 7 days and five by the 8-14th day from onset. Thirty-six children had multiple residual impairments, including twelve who were severely handicapped. The prognosis for both life and sequelae was significantly poor for herpes simplex encephalitis in etiologically diagnosed patients. We stress the importance of an increase in the vaccination rate and the establishment of an early diagnostic system.

462 patients (269 males, 193 females, aged from 1 month to 16 years) with encephalitis were treated at the Children's Hospital, University of Helsinki, over a 20-year period. The incidence of encephalitis was 8.3/100,000 child-years (range 19.8 in 1974 to 2.5 in 1985 and 1986). The organisms most commonly associated with encephalitis in children were mumps, measles, and varicella viruses, and Mycoplasma pneumoniae. After the start of the nationwide measles, parotitis, and rubella (MPR) vaccination programme in 1982 in Finland, encephalitides associated with these viruses seem to have totally vanished. Currently the pathogens most often associated with childhood encephalitides are varicella-zoster, M pneumoniae, and enteroviruses. 3% of the 462 patients died from their illness, and 7% became severely damaged, with the poorest outcome occurring after multiple infections, and herpes simplex virus, cytomegalovirus or M pneumoniae infections. The decline in the total number of cases of encephalitis was not accompanied by a decrease in number of patients with a poor outcome. Patients with treatable encephalitides due, for example, to M pneumoniae and herpes viruses, need prompt attention.

Acute encephalitis caused by Toxoplasma gondii was diagnosed in ten patients in Belgium, the U.S.A., and Canada. None had underlying conditions usually associated with toxoplasmosis. Three had evidence of extraneural infection at necropsy. Nine patients died. Only two of the patients had a history of homosexuality, and one was a heroin addict. Five were Haitian, and four of them had lived in North America for 2-5 years. Eight of the patients had pronounced lymphopenia. Diagnosis of toxoplasmosis was hampered by a lack of suspicion that Toxoplasma could be the agent causing necrotising encephalitis in the non-immunocompromised host, the protean manifestations of the encephalitis, and a lack of a specific antibody response. The large number of cases appearing in western Europe and North America emphasise the necessity of including toxoplasmosis in the differential diagnosis of encephalitis of unknown aetiology.

A study of routine data on mumps in England and Wales suggests that its epidemiological features are changing from those of an epidemic disease in young adults and older children to a more endemic disease in younger children. Infection now occurs at an earlier age, at which complications are less frequent and symptomless infection may be more common. The incidence of clinical disease may be falling. The high proportion of registered deaths in the middle aged and elderly may be an artifact due to misclassification of causes of death and to misdiagnosis. These changes lessen the need for routine immunisation. Indeed with low acceptance rates of measles vaccination of 50% at age 15 months, mumps/measles routine vaccination at the same age is contraindicated because similarly low acceptance rates might lead to an increase in the number of cases of mumps in older children and young adults, at which ages complications are more frequent.