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PubMed1993

Distribution of herpes simplex virus DNA in the brains of human long-term survivors of encephalitis.

We have examined the distribution of type 1 herpes simplex virus (HSV-1) DNA in the brains of 8 humans surviving for between 4 months and 17 years after acute encephalitis. Histological examination showed neuronal loss and gliosis largely confined to the temporal and frontal lobes, typical of HSV-1 encephalitis. There was a widespread persistent inflammatory infiltrate, present in both the cerebrum and brainstem. Viral DNA was detected in paraffin sections of formalin-fixed paraffin-embedded autopsy brain by use of the polymerase chain reaction to amplify a fragment of the HSV-1 thymidine kinase gene. HSV-1 DNA was amplified from the cerebrum in 6/8 cases and from the brainstem in 4/8 cases. These findings suggest the possibility that HSV-1 may persist within the human central nervous system after acute herpes simplex encephalitis. The distribution of the viral DNA correlates better with that of the persistent inflammatory infiltrate than with the destructive lesions of the acute encephalitis.

Adult↗
PubMed2006

The percipient observations of Constantin von Economo on encephalitis lethargica and sleep disruption and their lasting impact on contemporary sleep research.

The study, and the preceding companion article, reviews the pioneering contributions of Constantin von Economo (1876-1931) to Neuroscience in a modern context. The neurological studies of von Economo include the discovery of a new nosological entity, encephalitis lethargica, with which his name is forever linked ('von Economo disease'). Based on a percipient analysis of pathoanatomical material from patients with encephalitis lethargica who manifested with either insomnia or somnolence, von Economo deduced the existence of distinct centres in the brain for the regulation of sleep and wakefulness. He presented a synthesis of his ideas in a series of lectures in New York in 1929 and at the First International Neurological Congress held in Berne in 1931. Constantin von Economo was nominated three times for the Nobel Prize in Physiology or Medicine for the discovery of encephalitis lethargica. As those studies have exerted and continue to exert the highest impact among von Economo's publications, the present article examines the spectrum of his observations on encephalitis lethargica and the cerebral control of sleep, documented in 63 published works--including post-humous translations into French and English of original German texts; complete bibliographic information is given. His remaining 76 works of an annotated total of 139 scientific publications deal with brain structure, evolution and intelligence, as well as general works on nervous and mental pathology and form the focus of the preceding article.

Biomedical Research↗
PubMed2006

Alteration of regional cerebral blood flow to thyrotropin-releasing hormone therapy in acute encephalitis and encephalopathy during childhood.

BACKGROUND: Thyrotropin-releasing hormone (TRH) is now used as a therapeutic agent for various neurological disorders. Animal study has shown that TRH was attributable to increased cerebral blood flow (CBF). AIMS: There have been occasional reports that TRH therapy was effective for improving symptoms of persistent disturbance of consciousness after acute encephalitis or encephalopathy during childhood. To determine whether TRH has an effect on increasing CBF to patients who have consciousness disturbance caused by acute encephalitis or encephalopathy, and to determine the optimal method of administration. METHODS: Sixteen patients aged 0.7-10.9 years (mean age, 3.2+/-3.1 years) who presented with persistent disturbance of consciousness resulting from acute encephalitis or encephalopathy and were treated with TRH. Regional CBF (rCBF) was measured by single photon emission computed tomography before and after TRH therapy. The alteration rates of rCBF were compared between the divided two groups concerning the dose levels, dosing periods, and treatment lags. RESULTS: The alteration rates of rCBF of the high dose group were higher than those of the low dose group. Differences in the dosing periods and treatment lags did not cause any significant difference of the alteration rates of rCBF. CONCLUSION: The study showed that higher alteration rates of the CBF were observed in the higher dosing group, and TRH have the potency of increasing CBF. TRH therapy would have the potential for effective treatment of persistent consciousness disturbance caused by childhood acute encephalitis or encephalopathy.

Autoradiography↗
PubMed2005

Minocycline delays disease onset and mortality in reovirus encephalitis.

Minocycline is neuroprotective in many experimental models of neurodegenerative diseases and central nervous system (CNS) injury but has not previously been tested in a model of viral encephalitis. Experimental infection of neonatal mice with neurotropic reoviruses is a classic model for studying the pathogenesis of viral encephalitis. Intracerebral inoculation of serotype 3 reovirus strain Dearing (T3D) in neonatal mice results in lethal encephalitis caused by neuronal apoptosis throughout the CNS. Minocycline significantly delayed death in mice to 11.6 +/- 0.9 days post-infection vs. 8.6 +/- 0.7 days post-infection in controls (P < 0.01). Virus-induced CNS injury, apoptosis, viral titer and antigen expression were significantly decreased in the brains of minocycline-treated mice on 6 and 8 days post-infection compared to controls. Virus-induced injury and viral titer in minocycline-treated infected mice at 11 days post-infection were similar to those seen in untreated T3D-infected mice at 8 days post-infection. Little microglial or astrocytic invasion of brain regions with viral injury was found at any time-point in untreated or minocycline-treated mice, suggesting that in this model system the neuroprotective effect exerted by minocycline is more likely due to its anti-apoptotic properties rather than its capacity to inhibit microglial activation and limit gliosis. These findings, similar to those reported for neurodegenerative diseases, indicate that minocycline does not prevent development of fatal reovirus encephalitis but delays disease onset and progression, suggesting that minocycline treatment may provide a useful adjunctive therapy in viral CNS infections.

Age of Onset↗
PubMed2004

OTK18 expression in brain mononuclear phagocytes parallels the severity of HIV-1 encephalitis.

OTK18 was isolated by mRNA differential display of human monocyte-derived macrophages (MDM) infected with human immunodeficiency virus type one (HIV-1). Northern blot and real-time reverse transcription polymerase chain reaction showed low levels of OTK18 expression in human tissue, which markedly increased during advanced HIV-1 encephalitis (HIVE). Immunocytochemistry, using rabbit polyclonal antisera, showed OTK18 localized to brain mononuclear phagocytes (MP) in moderate to severe HIV-1 encephalitis. OTK18 expression was selective and not found in HIV-1-infected brain tissue with limited neuropathological abnormalities, nor in cytomegalovirus encephalitis, multiple sclerosis, Alzheimer's disease, or uninfected control brains. Thus, OTK18 expression in brain mononuclear phagocytes is a signature for advanced HIV-1 encephalitis.

AIDS Dementia Complex↗
PubMed2004

[A case of Influenza virus encephalitis in south of France].

INTRODUCTION: Influenza virus outbreaks occur each year, in France, during autumn and winter. Influenza-associated acute encephalitis were reported during epidemics or pandemics. Sporadic cases are rarely identified probably because influenza virus is not searched among etiology of febrile encephalitis. EXEGESIS: We report a case of influenza-associated encephalitis complicated by adrenal insufficiency in a young woman. Diagnosis was based on seroconversion of serum influenza virus A antibodies (complement fixation test). Follow up of the patient showed a total recovery. CONCLUSION: Influenza must be searched for any febrile encephalitis occurring during winter. Reverse transcriptase polymerase chain reaction (RT-PCR) on cerebrospinal fluid should be assessed. It is not actually a routine technique and we do not know yet if it is accurate enough for diagnosis. So, it is important to identify influenza virus and obtain documentary evidence concerning neurological impairment. Nevertheless, a better understanding of pathogenesis and use of vaccination are needed to improve prognosis.

Adult↗
PubMed1996

Neural cells from dogs with spontaneous distemper encephalitis express class II major histocompatibility complex molecules.

Expression of class II major histocompatibility complex (MHC) molecules by non-immune cells (e.g., parenchymal cells) leads to the presentation of self-antigens, and may have a role in the pathogenesis of many diseases mediated by autoimmunity. Such diseases, characterized by demyelination of the central nervous system and expression of class II MHC molecules on neural cells, include multiple sclerosis, experimental allergic encephalitis and Theiler's murine encephalomyelitis virus infection. Canine distemper encephalitis probably does not have an autoimmune character, but it shares many similarities with the aforementioned diseases. For this reason, the expression of class II MHC molecules in the brains of dogs with canine distemper encephalitis was investigated immunohistochemically. The results presented here demonstrate that canine microglia and astrocytes "upregulate" class II MHC expression in cases of encephalitis associated with chronic canine distemper.

Animals↗
PubMed2001

Seizures in Japanese encephalitis.

OBJECTIVE: Although Japanese encephalitis (JE) has been reported to be associated with seizures, there is no report on its frequency, pattern and severity and their correlation with electroencephalography (EEG) and radiological findings. In this communication, the analysis of seizures in 65 JE patients seen during 1991-1999 is presented. METHODS: The diagnosis of JE was based on clinical, radiological and serological criteria. The patients were subjected to a detailed clinical evaluation. Frequency and pattern of seizures and other neurological findings were recorded. Cranial CT scan or MRI was carried out in all the patients. Electroencephalograph was recorded using the 10-20 system of electrode placement. Patients' outcome was defined, on the basis of clinical status for 3 months, into poor, partial and complete recovery. The relationship between seizures and other clinical, radiological and EEG parameters was evaluated by the Z test of proportion using the two-tail approach. RESULTS: The patient's age ranged between 2 and 57 years, 24 were females and 19 were below 13 years of age. Thirty patients had seizures within the first week of encephalitis. The seizures were generalised tonic-clonic in 17 patients and partial motor with secondary generalization in 13 patients. Eleven patients had a single seizure, 8 had two seizures and 11 had multiple seizures. Two patients were presented with status epilepticus. Interictal EEG in the patients with seizures revealed theta to delta slowing in all patients and epileptiform discharges in four patients only. MRI revealed thalamic lesions bilaterally in 24, cortical in 7, basal ganglia in 8 and brainstem in 3 patients out of 26 patients with seizure. In the seizure group, three patients died, nine had poor, eight had partial and nine had complete recovery. Upon comparison of the JE patients with and without seizures, Glasgow coma scale (GCS) score, focal weakness, EEG slowing and cortical and thalamic lesion on CT or MRI were significantly related to the occurrence of the seizures; however, it was not associated with poor outcome. CONCLUSIONS: JE is associated with seizures in 46% of the patients in the acute stage of encephalitis which is easily controlled by monotherapy. Patients with severe encephalitis were associated with higher frequency of seizures.

Adolescent↗
PubMed1993

Viral encephalitis.

Viral encephalitis represents an important source of morbidity and mortality worldwide. Numerous viruses possess neurovirulence, producing encephalitic disorders that usually consist of fever, headache, vomiting, altered consciousness, focal or generalized seizures, and motor dysfunction. Contemporary virologic methods frequently allow rapid and specific identification of viral pathogens, but the etiologic agent remains uncertain in 25% or more of encephalitis patients. Although acyclovir substantially reduces mortality and improves outcome for patients with herpes simplex virus encephalitis, supportive care remains the only therapy available for most patients with virus encephalitis.

Antiviral Agents↗
PubMed2002

[Neuroleptic malignant syndrome in patients with non-herpetic viral encephalitis. Study of 7 cases].

BACKGROUND: Our aim was to consider the possibility that patients with viral non-herpetic viral encephalitis develop the neuroleptic malignant syndrome (NMS) and determine the indispensable elements to diagnose it. PATIENTS AND METHOD: Seven patients with this type of encephalitis whose clinical picture fulfilled the criteria for NMS were evaluated. The control group consisted of 17 patients with the same type of encephalitis who had been randomly selected from the Neurological Service of a 3rd level hospital. We compared blood leukocyte numbers, cerebrospinal fluid (CSF) findings, axilar temperature, creatine kinase (CK) values and number of days of hospitalisation. RESULTS: There were 5 males and 2 females with the mean age of 26 years. The control group consisted of 10 males and 7 females with an mean age of 37.52 years. Patients developed NMS after they were exposed to a mean doses of 17.85 mg of haloperidol with a latency (up to onset of symptoms) of 27.42 hours. In patients with NMS, the total number of leukocytes was increased (p < 0.003) as was that of neutrophils (p < 0.0003); the CSF protein level was increased (p < 0.02) whereas the CSF glucose level was reduced (p < 0.004); hyperpyrexia was higher (p < 0.000001); serum CK levels were higher (p < 0.000001), and, finally, NMS patients spent more days in hospital (p < 0.0002) than the control group. CONCLUSIONS: Patients with non-herpetic viral encephalitis can develop NMS after being exposed to relatively low doses of haloperidol and after a short latency period. The criteria typical of NMS including rigidity, hyperpyrexia, autonomic instability, altered consciousness and high CK levels are critical elements for its diagnosis. Moreover, these patients had high protein and low glucose CSF levels and they require more days of hospitalisation.

Adolescent↗
PubMed1996

The patterns of varicella zoster virus encephalitis.

Varicella zoster virus (VZV) encephalitis has become increasingly prevalent in the era of acquired immunodeficiency syndrome (AIDS), and a widening spectrum of pathological lesions has defined the disease in these and other severely immunosuppressed patients. VZV produces three distinct morphological patterns of brain damage. VZV can cause bland or hemorrhagic infarctions secondary to a large or medium vessel vasculopathy. Deep white matter, ovoid mixed necrotic, and demyelinative lesions occur as a consequence of small vessel vasculopathy, with demyelination dependent on the degree of additional oligodendrocyte infection. Distinctive Cowdry A intra-nuclear viral inclusions are rare in either large or small blood vessels or near infarctions, but are commonly found in glial cells at the edge of the smaller ovoid, demyelinative lesions. Ependymal and periventricular necrosis occurs as a result of vasculopathy of subependymal vessels and secondary infection of ependymal and other glial cells in the periventricular region. To clarify these patterns of VZV encephalitis and shed light on their pathogenesis, the authors have examined all cases of VZV encephalitis seen at our institution since 1984. Additionally, the authors review the extensive literature in an attempt to classify the patterns of VZV encephalitis into (1) large/ medium vessel vasculopathy with bland or hemorrhagic infarctions, (2) small vessel vasculopathy with mixed ischemic/demyelinative lesions, and (3) ventriculitis/periventriculitis. Although one of these three patterns often predominates clinically and radiographically, careful histological examination at autopsy shows mixed features in many cases.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

A large outbreak of acute encephalitis with high fatality rate in children in Andhra Pradesh, India, in 2003, associated with Chandipura virus.

BACKGROUND: An outbreak of acute encephalitis of unknown origin with high case fatality (183 of 329 cases) was reported in children from Andhra Pradesh state in southern India during 2003. We investigated the causative agent. METHODS: Cell lines and peripheral blood lymphocyte co-cultures were used to isolate the causative agent from clinical samples. Identity of the agent was established by electron microscopy and serological and molecular assays. FINDINGS: Clinical samples tested negative for IgM antibodies to Japanese encephalitis, West Nile, dengue, and measles viruses, and for RNA of coronavirus, paramyxovirus, enterovirus, and influenza viruses. Virus was isolated from six patients with encephalitis and was identified as Chandipura virus by electron microscopy, complement fixation, and neutralisation tests. Chandipura virus RNA was detected in clinical samples from nine patients. Sequencing of five of these RNA samples showed 96.7-97.5% identity with the reference strain of 1965. Chandipura viral antigen and RNA were detected in brain tissue of a deceased child by immunofluorescent antibody test and PCR. Neutralising, IgG, and IgM antibodies to Chandipura virus were present in some patients' serum samples. Serum samples obtained after 4 days of illness were more frequently positive for IgM to Chandipura virus than were those obtained earlier (p<0.001). A similar trend was noted for neutralising antibodies. INTERPRETATION: Our findings suggest that this outbreak of acute encephalitis in Andhra Pradesh was associated with Chandipura virus, adding to the evidence suggesting that this virus should be considered as an important emerging pathogen.

Acute Disease↗
PubMed1989

Effect of measles, mumps, rubella vaccination on pattern of encephalitis in children.

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.

Adolescent↗
PubMed1998

PCR on cerebrospinal fluid to show influenza-associated acute encephalopathy or encephalitis.

BACKGROUND: Except for Reye's syndrome, influenza-associated acute encephalopathy or encephalitis is not universally recognised. We did a multicentre study of laboratory and clinical data for patients with influenza-associated acute encephalopathy or encephalitis. METHODS: In Nagoya, Japan, ten patients with acute encephalopathy or encephalitis associated with influenza-like illness were admitted to our hospitals between April, 1996, and March, 1997. We collected clinical, laboratory and serological data and assessed cerebrospinal fluid samples by PCR for influenza A and B. FINDINGS: Seven patients, aged 22 months to 4 years, had evidence of recent influenza infection, six with type-A/Hong Kong (H3N2) and one with type B. The first sign in the central nervous system appeared within 2 days of fever in all but one patient. The first sign of involvement of the central nervous system was generalised convulsions in all patients. Two patients died, one had sequelae, and four survived without sequelae. PCR for influenza type A was positive for five patients. INTERPRETATION: The results of PCR suggest that at least part of the influenza type A genome existed in the central nervous system. Influenza-associated acute encephalopathy or encephalitis in young children deserves wider recognition.

Acute Disease↗
PubMed1994

Cytomegalovirus encephalitis in two patients with AIDS receiving ganciclovir for cytomegalovirus retinitis.

Cytomegalovirus (CMV) encephalitis has been reported with increasing frequency in patients with AIDS. Nevertheless, the management of CMV-related encephalitis appears to be problematic and data in the literature on the clinical efficacy of ganciclovir therapy is sparse and controversial. We describe two patients with AIDS who developed CMV encephalitis while receiving ganciclovir maintenance therapy for CMV retinitis. Moreover, there was no improvement in neurological status or virological and radiological response during a further induction course of ganciclovir. These observations suggest that the currently recommended therapeutic protocols with ganciclovir are not effective in the prevention and treatment of CMV encephalitis in patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1985

Chronic mumps virus encephalitis. Mumps antibody levels in cerebrospinal fluid.

To study the outcome of mumps virus encephalitis 47 patients were contacted 1-15 years after the acute encephalitis associated with mumps virus infection. Twenty-three patients experienced clinical sequelae such as difficulties in memory and learning, focal motor or sensory signs, and loss of hearing and visual acuity. Lumbar puncture was performed on 8 patients. Antibodies to mumps virus were detected in 6 cerebrospinal fluid (CSF) specimens using enzyme immunoassay and in 3 patients an abnormal serum/CSF antibody ratio was observed 11, 26 and 58 (controls greater than 85); 14.3, 1.4 and 6.1 years after the acute encephalitis, respectively. Antibodies to other microbes were either undetectable in the CSF or the serum/CSF ratios were normal. The clinical sequelae in about half of the patients and the signs of intrathecal mumps antibody production are suggestive of a chronic process in the central nervous system after encephalitis associated with mumps virus infection.

Adult↗
PubMed1988

Antiviral treatment of a serious herpes simplex infection: encephalitis.

Herpes simplex encephalitis is the most common cause of sporadic encephalitis in the western world. Patients usually have altered levels of consciousness, altered levels of mentation, fever, headache, and personality changes. These may progress to hemiparesis and seizures. Exact diagnosis must be established by brain biopsy and identification of the virus in biopsy material. There is a great need for a noninvasive test that is positive early in the disease. Without antiviral treatment the mortality rate is greater than 70%, and many survivors have serious disabilities. Both adenine arabinoside and acyclovir decrease death and morbidity, but acyclovir is the preferred drug. With acyclovir about 40% of patients will survive with normal development or minor levels of impairment but more than half of the patients will die or suffer significant impairment. It is essential to treat early; patients who are young and have not reached coma or impaired consciousness may show 65% recovery and return to normal function. Development of new antiviral drugs or other types of therapies is desirable. Herpetic skin lesions are likely to be more confusing than diagnostic because other types of encephalitis with fever often precipitate recurrent herpes that is unrelated to the encephalitis.

Acyclovir↗
PubMed1999

[A cause of acute encephalitis: primary infection due to Epstein-Barr virus].

UNLABELLED: The neurologic complications of Epstein-Barr virus (EBV) primary infection are frequently overlooked, yet EBV is responsible for some cases of acute encephalitis. We report on a case of an infant with acute brain-stem encephalitis during EBV primary infection. OBSERVATION: A 22-month-old boy was admitted to the hospital for acute neurological symptoms. Initially, he presented ataxia and dysphagia. During the first days, his neurological status worsened with loss of consciousness requiring ventilatory support. A progressive improvement appeared after a 1 week course. One month later, a moderate ataxia was still noted, but 3 months later, the clinical examination was normal. The neuroradiological explorations revealed damage of the white matter, with high T2-weighed signal on the first brain magnetic resonance imaging. One month later, the control magnetic resonance imaging was normal. The diagnosis of EBV encephalitis was based upon the exclusion of other possible causes and positive serology for EBV, consistent with acute primary infection. CONCLUSION: EBV infection should be looked for during the etiologic work-up of an acute encephalitis. The different cases reported in the literature show a favorable initial outcome, but neurological relapse and sequelae are possible. No specific treatment is effective.

Acute Disease↗