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Atypical brainstem encephalitis caused by herpes simplex virus 2.

BACKGROUND: Herpes simplex encephalitis is one of the most common and serious sporadic encephalitides of immunocompetent adults. Herpes simplex virus 2 (HSV-2) infections of the central nervous system usually manifest as subacute encephalitis, recurrent meningitis, myelitis, and forms resembling psychiatric syndromes. OBJECTIVES: To report and discuss magnetic resonance imaging (MRI) findings and clinical features in atypical brainstem encephalitis and facial palsy associated with HSV-2. SETTING: Neurology department of a tertiary referral center. PATIENT: A 37-year-old woman was admitted to the hospital with fever, diplopia, left hemiparesis, sensory change in the face and limbs, personality changes, frontal dysexecutive syndrome, and a stiff neck. Brain MRI showed multifocal high-signal intensities in the pons, midbrain, and frontal lobe white matter on T2-weighted and fluid-attenuated inversion recovery images. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) amplification analysis was positive for HSV-2. Acyclovir therapy was started, and the encephalitic symptoms disappeared with a negative conversion of HSV-2 PCR in the CSF. However, after the discontinuation of acyclovir therapy, peripheral facial palsy occurred on the left side. A possible relapse or delayed manifestation of the HSV-2 infection was suspected, and the acyclovir therapy was restarted. A complete remission was achieved 3 days after the treatment. She was discharged without any neurologic sequelae. CONCLUSIONS: We describe a patient who developed atypical encephalitis due to HSV-2 and peripheral facial palsy, which could also be related to the HSV-2. This case suggests that HSV-2 should be considered among the possible causes of atypical or brainstem encephalitis and that the PCR amplification method of the CSF can help reveal the possible cause of HSV-2.

Acyclovir↗

The predictive value of cytomegalovirus retinitis for cytomegalovirus encephalitis in acquired immunodeficiency syndrome.

Cytomegalovirus (CMV) infection of the brain, optic nerves, and retinas from 47 consecutive autopsies of patients with acquired immunodeficiency syndrome (AIDS) were examined. Immunocytochemistry demonstrated CMV infection in 11 (23%) brains, two (2%) of 94 optic nerves, and 38 (40%) of 94 retinas. Ten (91%) of 11 patients with CMV encephalitis had concurrent retinitis. While 10 (42%) of 24 patients with CMV retinitis had CMV encephalitis, when the retinitis included the peripapillary region, 75% had encephalitis. Usually, the optic nerve parenchyma was not infected histologically despite extensive peripapillary retinitis. The strength of these associations suggests that CMV retinitis defines a group of patients with AIDS at risk for development of CMV encephalitis (relative risk, 9.5), particularly when the retinitis involves the peripapillary region (relative risk, 13). Furthermore, in patients with AIDS without CMV retinitis, central nervous system symptoms are unlikely to be attributable to CMV encephalitis.

AIDS-Related Opportunistic Infections↗

Human immunodeficiency virus encephalitis is the pathological correlate of dementia in acquired immunodeficiency syndrome.

While dementia has been observed in approximately one-fourth of terminally ill patients with acquired immunodeficiency syndrome, it has been difficult to attribute this clinical disorder to a single neuropathological substrate. We used a simple and readily reproducible scale for estimating the burden of human immunodeficiency virus (HIV) in the central nervous system (i.e., severity of HIV encephalitis) and compared this to autopsy neurological summaries of dementia. Like others, we found that multinucleated giant cells were present in only half of the dementia patients. However, all of the dementia patients had severe HIV encephalitis as assessed by measurements of intra-central nervous system viral burden. Additional patients had severe HIV encephalitis without clinical histories of dementia. We interpret these latter findings as evidence that HIV encephalitis exists for a period of time before the clinical symptomatology develops. Comparison of presence or absence of concurrent cytomegalovirus encephalitis showed no association with dementia.

AIDS Dementia Complex↗

Screening for possible failure of herpes simplex virus PCR in cerebrospinal fluid for the diagnosis of herpes simplex encephalitis.

The objectives of this study were to evaluate the reliability of herpes simplex virus (HSV) PCR testing in cerebrospinal fluid (CSF) for the detection of herpes simplex encephalitis. This was done by examining retrospectively the clinical follow-up of a large group of patients tested routinely by HSV-PCR. In addition, an attempt was made to assess the incidence of herpes simplex encephalitis in a central European population. CSF samples from 1,427 patients from all Vienna hospitals were submitted for HSV-PCR testing during a period of 4 years and 8 months. Herpes simplex encephalitis was detected by PCR in 12 cases and by serological methods in one additional patient. Retrospective analysis of the course of disease, which was possible in 799 PCR-negative patients, led to the identification of three additional cases in which herpes simplex encephalitis appears to have occurred despite negative PCR results. Failure of the PCR in these patients is most likely due to the time of obtaining CSF during the course of disease. A high specificity of the assay was demonstrated by the lack of false positive results in any of the 708 cases in which other causes for the neurological symptoms had been identified in the follow-up. The incidence of herpes simplex encephalitis in the population of Vienna was between 1 case/469,000-577,000 individuals/year. The highest annual incidence was detected in the age group between 3 months and 3 years, which, however, could not be confirmed statistically.

Adolescent↗

Non-herpes simplex encephalitis is early exclusion of herpes simplex etiology possible?

Since effective antiviral treatment is available for herpes simplex encephalitis (HSE), early diagnosis or exclusion of herpes simplex etiology is essential for prognosis. In a retrospective study of 25 cases of acute viral encephalitis not caused by herpes simplex virus (non-HSE), we investigated whether HSE can be excluded in the early phase before serological evidence is present. Using clinical means, history, investigations of CSF (protein, cells), EEG, and CCT, HSE could not be excluded with reliability. This is because clinical signs and laboratory results are not pathognomonic for any form of viral encephalitis, even if periodic activity in EEG and temporal attenuation in CCT are more frequent in HSE than in other forms of encephalitis. Therefore, in all cases of severe encephalitis, acyclovir therapy should be initiated early.

Adolescent↗

Cerebrospinal fluid levels of soluble tumour necrosis factor receptor in acute encephalitis.

Soluble tumour necrosis factor receptor (sTNF-R) inhibits the action of TNF-alpha. The level of sTNF-R reflects the true biological activity of TNF-alpha. We investigated whether sTNF-R in cerebrospinal fluid (CSF) and serum increases during the acute stage in patients with acute encephalitis by measuring p60 sTNF-R using a sandwich enzyme immunoassay. The levels of sTNF-R were significantly higher in the CSF and serum of children with acute encephalitis than in those of control subjects. The patients with acute encephalitis who died or had severe neurological sequelae had higher CSF sTNF-R levels than those who survived. There were no significant differences in the serum sTNF-R, serum C-reactive protein and CSF protein levels, and CSF cell counts between the two groups. The sTNF-R levels of 4.0 ng/ml or higher identified patients with acute encephalitis who had neurological sequelae with a sensitivity of 100% (8/8), a specificity of 100% (8/8%), and a predictive value of 100% (8/8). The 95% confidence interval for these three values is 63-100%. Our findings suggest that the CSF level of sTNF-R during the acute stage of encephalitis is important for predicting neurological sequelae.

Acute Disease↗

Detection of viral antigens in cerebrospinal fluid of rabbits with experimental herpes simplex virus type 1 encephalitis.

We investigated several methods for the rapid diagnosis of herpes simplex virus induced encephalitis in a rabbit model. The corneas of twenty-two rabbits were infected with herpes simplex virus type 1 (HSV-1) and diagnosis of Herpes encephalitis was made by virus isolation, immunofluorescent and peroxidase staining of brain biopsies, demonstration of anti-HSV IgM in cerebrospinal fluid (CSF) and by an indirect enzyme-linked immunosorbent assay (ELISA), designed for detection of viral antigens. With the last method we were able to demonstrate viral antigens in cerebrospinal fluid six days post infection, before clinical signs of encephalitis appeared. In three rabbits this was before anti-HSV IgM appeared in the CSF. Virus was isolated from brain samples of 67 per cent of the animals which died from Herpes encephalitis. Nine rabbits received cortisone before infection, resulting in markedly lower antibody titers and a higher lethality, 77 per cent, as compared to 46 per cent in nontreated rabbits. For rapid diagnosis of Herpes encephalitis in rabbits, demonstration of herpes simplex virus antigens in CSF by means of an indirect ELISA is superior to the other methods investigated.

Animals↗

Epstein-Barr virus encephalitis and encephalomyelitis: MR findings.

The purpose of this project is to investigate the clinical and brain MR characteristics of Epstein-Barr virus (EBV) encephalitis and encephalomyelitis. Clinical and 30 MR findings of 29 patients with EBV encephalitis or encephalomyelitis were retrospectively reviewed. Patients included 24 with encephalitis, 3 with encephalomyelitis, and 2 with brain-stem encephalitis. Altered consciousness, seizures, visual hallucination, and acute psychotic reaction were the common presentations. Eight patients had positive MR findings. These included T2 prolongation over gray and white matter, periventricular leukomalacia, and brain atrophy. Transient T2 prolongation over gray and white matter was found in one patient. Our results indicate that EBV encephalitis and encephalomyelitis have a wide range of both clinical and MR findings. The MR lesions may disappear in a short period, so the timing for the MR scan may be critical.

Adolescent↗

Acyclovir monotherapy versus acyclovir plus beta-interferon in focal viral encephalitis in children.

Severe focal viral encephalitis is most commonly caused by herpes simplex virus (HSV), but other viruses may act as etiologic agents as well. Acyclovir (ACV) is the standard therapy for HSV encephalitis, but the mortality of 28% and defect healing rate of about 35% are still unsatisfactory. Furthermore, ACV has virtually no effect on other pathogens of viral encephalitis, except for varicella-zoster virus (VZV). It is well known that beta-interferon (beta-IFN) has a broad antiviral spectrum, and it has been demonstrated in vitro that beta-IFN in combination with acyclovir has synergistic inhibitory effects on HSV. To investigate if the combination of ACV with and without beta-IFN might also be of significance for the treatment of severe viral encephalitis, we performed a retrospective study. A case record form was sent to all 278 West German children's hospitals. The response rate was 78%. A total of 301 patients were reported, of whom 214 received specific antiviral therapy with either ACV alone (n = 179) or ACV plus beta-IFN (n = 35). No overall differences between ACV monotherapy and the combination therapy were observed. However, in a subgroup of 41 patients (ACV n = 30, ACV plus beta-IFN n = 11) who had low-density areas of the temporal lobes on cranial computed tomography scans, compatible with severe focal encephalitis, sequelae due to defect formation and mortality were significantly (p = 0.014) reduced in patients who had received combination therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗

Cytomegalovirus encephalitis in an immunocompetent pregnant woman.

Presented here is the case of an immunocompetent pregnant woman with probable cytomegalovirus encephalitis. The clinical picture was characterized by diffuse headache, drowsiness and the development of an acute confused state. Diagnosis was based on the documentation of recent cytomegalovirus seroconversion with low avidity for the immunoglobulin G class antibodies. Initially, the diagnosis of encephalitis was challenging due to the subtle findings in cerebrospinal fluid and the normal electroencephalograph results. However, repeated tests revealed findings compatible with the diagnosis of encephalitis. Due to the suspicion of herpes simplex encephalitis the patient was treated with acyclovir. Within a few days rapid resolution of the fever and complete recovery were observed. Cytomegalovirus encephalitis should be considered early in the evaluation of pregnant women if appropriate clinical symptoms are present.

Acyclovir↗

Viral encephalitis: neuropsychiatric and neurobehavioral aspects.

Viral encephalitis, a condition in which a virus infects the brain and produces an inflammatory response, affects approximately 20,000 individuals per year in the United States. The viral encephalidities include sporadic and epidemic acute viral encephalidities and subacute and chronic/progressive viral encephalitis or encephalomyelitis. In people who survive these conditions, postencephalitic impairments of elemental neurologic, cognitive, emotional, and behavioral function are common. This article will provide a brief overview of the diagnosis and acute management of acute viral infections of the central nervous system. The neurologic and neuropsychiatric features, neuropathologies, and treatments of two of the more common types of acute viral encephalitis in North America--herpes simplex encephalitis and West Nile encephalitis--will be reviewed. The current and future role of psychiatrists and neuropsychiatrists in the care and study of individuals with these conditions will be discussed.

Acute Disease↗

BKV-DNA and JCV-DNA in CSF of patients with suspected meningitis or encephalitis.

BACKGROUND: Few studies have looked for the polyoma viruses JC or BK virus in the central nervous system (CNS) of patients without neurological symptoms or with neurological symptoms other than progressive multifocal leukoencephalopathy (PML). PCR-microplate hybridization method was employed for the detection of BKV-DNA or JCV-DNA in cerebrospinal fluid (CSF) specimens from patients with suspected meningitis or encephalitis. MATERIALS AND METHODS: A total of 181 CSF specimens from 151 patients with suspected meningitis or encephalitis was examined for BKV or JCV using PCR-microplate hybridization method. None of the patients had (clinically diagnosed) PML. A control group consisting of 20 CSF specimens from normal subject was also included. RESULTS: BKV DNA was found in five out of 131 (3.8%) and JCV DNA in two out of 131 (1.5%) of the patients with suspected meningitis or encephalitis by PCR ELISA. BKV or JCV DNA was not detected in CSF samples of any of 19 HIV positive patients. BKV and JCV DNAs were detected respectively in two CSF samples in which Mycobacterium tuberculosis (TB) PCR was also positive. Another patient who was positive for JCV PCR died with a diagnosis of cerebral lymphoma. Among the BK virus infected patients there was a patient with a previous history of hemolytic uremia and acute renal failure. Neither BKV nor JCV DNA was found in any of the 20 CSF samples from normal patients undergoing lumbar puncture for myelography as a part of an investigation of lower back pain. CONCLUSION: These results suggest that BK virus may be associated with neurological diseases either in immunocompetent or immunocompromised patients. Detection of BKV and JCV DNA in the CSF of the patients suspected to have either meningitis or encephalitis suggests that these viruses may have an etiological role. Thus, diagnostic tests for BK and JC viruses should be included in the investigative program for meningitis or encephalitis patients.

Adult↗

Assessment of therapy for toxoplasma encephalitis. The TE Study Group.

Toxoplasma encephalitis has been reported as a life-threatening opportunistic infection among patients with the acquired immune deficiency syndrome. The TE Study Group was established to address clinical questions about Toxoplasma encephalitis by retrospectively reviewing available data. The medical centers selected were those reporting Toxoplasma encephalitis to the Centers for Disease Control or to one of the principal investigators. Sixty-eight histologically confirmed cases of Toxoplasma encephalitis were reported by investigators at 31 medical centers; 61 of the patients received some therapy. Overall prognosis was poor. The median survival following initiation of therapy was four months. Patients described as "alert" at initiation of therapy survived significantly longer than those described as "lethargic" or "stuporous." No beneficial or harmful effects could be attributed to the use of corticosteroids. Toxicity attributed to pyrimethamine and sulfonamide therapy was reported in 60 percent of patients. Leukopenia, rash, and thrombocytopenia were common during therapy. A clinical relapse of Toxoplasma encephalitis was reported in 50 percent of patients discharged from the hospital.

Acquired Immunodeficiency Syndrome↗

EEG and pathologic findings in patients undergoing brain biopsy for suspected encephalitis.

Previous studies have suggested that EEG may be helpful in the diagnosis of herpes encephalitis (HE). To further define the value of EEG in an acutely ill, febrile, encephalopathic patient suspected as having encephalitis, we reviewed initial preoperative EEGs with the results of cerebral biopsies in 24 consecutive patients suspected of having encephalitis. Statistical analysis demonstrated that EEG patterns have only limited association with biopsy results. Since diseases which mimic encephalitis may also generate identical EEG changes, this is not an unexpected finding. EEG is useful in the evaluation and management of patients with encephalitis. However, the absence of specific wave forms or focal EEG abnormalities in the proper clinical setting should not deter consideration of HE or delay treatment.

Adolescent↗

Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid.

With the aim of improving early diagnosis of herpes simplex encephalitis a polymerase chain reaction (PCR) assay with two "nested" primer pairs was developed for the amplification of herpes simplex virus DNA in cerebrospinal fluid (CSF). Southern blotting was used to confirm the specificity of the amplification. The assay was applied to 151 CSF samples from 43 consecutive patients with herpes simplex encephalitis verified by the finding of herpes simplex virus/viral antigen in a brain biopsy sample or at necropsy (13) and/or intrathecal production of IgG antibody to the virus (40). As controls, 87 CSF samples from 60 patients with acute febrile focal encephalopathy (initially suspected to be herpes simplex encephalitis but excluded by the absence of intrathecal antibody synthesis) were tested. PCR detected herpes simplex virus DNA in 42 of the 43 patients with proven herpes simplex encephalitis; all but 1 were positive in the first CSF sample taken. The 1 PCR-negative patient had been treated with acyclovir from 20 h after the onset of symptoms. All the control subjects were PCR negative, as were 270 internal contamination controls. The PCR result remained positive in samples drawn up to 27 days after the onset of neurological symptoms. This method is a rapid and non-invasive means to diagnose herpes simplex encephalitis; it is highly sensitive and specific.

Acyclovir↗

Epidemiology of acute childhood encephalitis. Aichi Prefecture, Japan, 1984-90.

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.

Adolescent↗

Longitudinal analysis of activation markers on monocyte subsets during the development of simian immunodeficiency virus encephalitis.

Lentiviral encephalitis has been hypothesized to be associated with altered monocyte migration into the brain. CD14(hi)/CD16(lo) and CD14(lo)/CD16(hi) monocytes were expanded during acute infection; however, this expansion was not unique or greater in macaques that developed encephalitis. The proportion of monocytes that expressed CD62L, HLA-DR, CD16, CD64, and CD40 varied during the course of infection in macaques that eventually developed encephalitis. Taken together, these results suggest that changes in the proportion of circulating activated monocytes are not predictive of development of encephalitis, but this does not rule out the importance of activated monocytes in the development of encephalitis.

AIDS Dementia Complex↗

Herpes simplex encephalitis: the role of surgical decompression.

BACKGROUND: The role of acyclovir for the treatment of herpes simplex encephalitis has been well documented, but the role of surgical decompression for herpes simplex encephalitis has only rarely been mentioned. The authors report two cases of herpes simplex encephalitis that involved surgical decompression. CASE DESCRIPTION: In the first case, a therapeutic regimen of acyclovir was begun on the 11(th) day of the clinical course, and surgical decompression was performed because of impending uncal herniation on the 13(th) day. In the second case, a therapeutic regimen of acyclovir was begun on the third day of the disease's clinical course, and surgical decompression was performed because of impending uncal herniation on the 11(th) day. Both patients had good neurological outcomes and were seizure-free 12 months after their surgical procedures. CONCLUSION: We conclude that, for patients with herpes simplex encephalitis, it is important for the clinician to detect deterioration of consciousness because of the mass effect caused by the disease-associated inflammatory process as early as is possible. Surgical decompression is indicated for impending uncal herniation or intolerable increased intracranial pressure. Such surgery can contribute to an improved outcome for patients with herpes simplex encephalitis.

Acyclovir↗