Differentiation of the humoral immune response in herpes simplex encephalitis

Six patients with herpes simplex encephalitis were investigated. Antibody activities against different viral antigens were determined in serum and cerebrospinal fluid with an enzyme-linked immunosorbent assay after adjusting both fluids to identical immunoglobulin G concentrations. In serum, the strength of the antiviral reaction remained low and no qualitative changes became detectable. In cerebrospinal fluid, at first locally synthesized antibodies were directed against the same antigens as in serum. Ten days later, the intrathecal reaction increased with additional antibodies against at least two antigens. Once established, this expanded heterogeneity remained stable during the course of the disease.     

Infiltration of immune T cells in the brain of mice with herpes simplex virus-induced encephalitis

Herpes simplex virus (HSV) infection of mice can induce viral encephalitis. Using two-fluorochrome immunofluorescence, our present study shows that though there is extensive myelin loss and necrosis in the brain stem of mice with HSV encephalitis, only some oligodendrocytes, astrocytes and microglial cells are infected. T cells that express CD4 or CD8 and a large number of CD4+, F4/80+ macrophages are present in perivascular infiltrates close to and in contact with HSV-infected cells in areas of massive myelin loss. These findings suggest that the resultant infiltration of immune cells into the brain during HSV-1 infection may cause as much damage as the virus itself.     

γ-氨基丁酸在小鼠单纯疱疹病毒性脑炎中的表达变化

目的:观察γ-氨基丁酸(GABA)在小鼠单纯疱疹病毒性脑炎(HSE)病程中的表达变化,探讨其在病毒感染性脑损伤中的作用。方法:颅内病毒直接接种的方法建立小鼠疱疹病毒性脑炎模型,免疫组化的方法同时检测疱疹病毒(HSV)抗原和GABA在脑炎不同时间的表达变化,结果用图像分析系统进行分析。结果:病毒接种3d后脑组织颞叶、额叶、海马均出现HSV抗原阳性细胞,7-10dHSV抗原阳性细胞数目达高峰,阳性面积比最大,部分脑组织出现坏死,14d后抗原阳性表达细胞开始减少。GABA的表达变化与HSV的表达呈相反趋势,其阳性神经元数目则随病程而减少,在病程的7-10d表达降至最低,部分标本脑组织的坏死区几乎无表达,14d后表达开始增强。结论:GABA的表达变化与病毒性脑炎的严重程度有一定的相关性,可能对感染性脑损伤具有保护作用。     

Electroencephalography in herpes simplex encephalitis

The EEG in the acute stage of herpes simplex encephalitis (HSE) can show a variety of abnormalities, including uni- or bilateral periodic sharp waves or attenuation of amplitude, focal or generalized slow waves or epileptiform discharges, or electrical seizures. No specific EEG patterns are pathognomonic for HSE, but a focal or lateralized EEG abnormality in the presence of encephalitis is highly suspicious of HSE. In the acute stage, EEG appears to be more sensitive than computerized tomography or radioisotope brain scanning. The EEG findings tend to differ in the course of illness, and the periodic discharges occur only during the acute stage. The EEG findings in either the acute stage or long-term follow-up do not predict the chance of survival or severity of disability, and EEG changes appear to lag behind the clinical changes. EEG results can become normal in both adults and neonates when the acute stage is over.     

Herpes simplex encephalitis with herpes simplex retinitis

The association of herpes simplex encephalitis and herpes simplex retinitis is rare in adults. The case presented indicates that the manifestation of retinitis after herpes simplex encephalitis is infectious and not immunologic in origin. Retinal infection results either from neuron-to-neuron transmission of viruses along the optic nerve or from recurrent viral infection. Treatment with acyclovir improves the otherwise rather poor prognosis of combined herpes simplex encephalitis and retinitis. In this case a second course of systemic treatment with acyclovir was effective.     

Acyclovir resistance in herpes simplex encephalitis

Herpes simplex virus type 1 is a common cause of severe sporadic encephalitis. Treatment with acyclovir is highly effective in this disease. We report the case of a 27‐year‐old, immunocompetent woman with acyclovir‐resistant herpes simplex encephalitis. Although she had not been treated before, herpes simplex virus type 1 DNA from the cerebrospinal fluid showed a non‐synonymous mutation in the thymidine kinase gene, which is likely to have caused resistance to acyclovir. Herpes simplex encephalitis resolved after treatment with foscarnet. To our knowledge, this is the first report of acyclovir‐resistant herpes simplex virus encephalitis in an immunocompetent, previously therapy‐naive adult. ANN NEUROL 2010;67:830–833     

Update on herpes simplex encephalitis

Herpes simplex encephalitis is the most common identified cause of sporadic viral encephalitis in the United States. Early diagnosis is critical because treatment with the antiviral drug acyclovir dramatically decreases morbidity and mortality. The use of polymerase chain reaction (PCR) techniques to amplify the genome of herpes simplex virus (HSV) from cerebrospinal fluid (CSF) has become the diagnostic procedure of choice. False-positive CSF HSV PCR results are rare when testing is performed in experienced laboratories. Negative CSF HSV PCR results should always be interpreted in the context of the timing of specimen collection and the likelihood of disease. Negative CSF HSV PCR tests can occur within the first 72 hours of illness, with subsequent tests becoming positive. Patients with HSV encephalitis will typically have a negative CSF HSV PCR after 14 days of acyclovir treatment, and a persisting positive PCR should prompt consideration of additional or revised antiviral therapy. Quantitative PCR testing provides information about HSV viral load in CSF, but the potential correlation of viral load with prognosis or other clinical features of disease remains uncertain. Although the neuroimaging abnormalities seen in HSV encephalitis are not unique, more than 90% of patients with proven HSV encephalitis will have magnetic resonance imaging (MRI) abnormalities involving the temporal lobes. Special MRI techniques, including fluid-attenuated inversion recovery and diffusion-weighted imaging, might reveal abnormalities not seen with conventional imaging sequences. Neuroimaging patterns in infants and children differ significantly from those seen in adults and include a higher frequency of extratemporal lesions.     

Relapse of herpes simplex encephalitis

This report describes a child with herpes simplex virus (HSV) encephalitis who improved dramatically while being treated with acyclovir but subsequently had neurological deterioration and died. A severe necrotizing process was present in the brain at autopsy but there were no focal areas of demyelination and poor inflammatory response. HSV was not cultured from brain biopsy during relapse or autopsy. Fourteen previous cases of relapsing herpes encephalitis are reviewed and treatment regime and mechanisms of relapse are discussed.     

EEG in neonatal herpes simplex encephalitis

The EEGs of 21 newborns with herpes simplex encephalitis were analysed. The diagnosis was based on the demonstration of herpes simplex infection in association with neurological symptoms, other etiological factors being excluded. Sixteen of 21 babies (76%) showed in their EEGs electrical seizures, either focal or unilateral. These paroxysms consisted of sharp waves or slow waves repeating at pseudo-periodic intervals, usually of 0.5-2 sec. Individual paroxysms had a duration of 10-20 sec in 6 babies and 1-2 min in 10 patients. During the same period, 20 other babies displayed the same EEG finding. Of these, 11 had encephalitis of unknown etiology. In our series there appeared to exist a correlation between both the duration of the electrical seizures and the degree of EEG background abnormality and the clinical outcome. Babies with markedly abnormal background and long-lasting paroxysms tended to have a poor prognosis. It is concluded that in newborns with clinical signs of encephalitis who show in their EEGs paroxysms of the type described, the possibility of herpes simplex encephalitis should be considered.     

Recent issues in herpes simplex encephalitis

Herpes simplex encephalitis (HSE) remains the most important cause of fatal sporadic encephalitis in man. Caused by herpes simplex virus type 1 (HSV-1), and more rarely by HSV-2, it can have devastating clinical consequences for the patient, especially when the instigation of acyclovir therapy has been delayed by more than 2 days or more. Even with acyclovir treatment, nearly a third of patients may die or suffer significant morbidity. Both host and viral factors may interact to affect the clinical phenotype. Here we consider some of the recently published management guidelines for HSE and comment on various current issues of contention. The latter includes the timing and frequency of cerebrospinal fluid examinations for the polymerase chain reaction detection of HSV, decisions regarding acyclovir therapy including the consequences of delay in its initiation, and the use of corticosteroids in the disease.     

Naming deficit in herpes simplex encephalitis

Objectives – The preferential involvement of living categories in naming impairment is well recognised in Herpes Simplex Encephalitis (HSE). In this paper we describe naming, neuropsychological and neuroradiological findings with seven fresh HSE cases. Material & methods – Patients were given a picture naming task that included 60 items belonging to 6 different categories (three living, i.e. fruits, vegetables and animals and three nonliving, i.e. furniture, vehicles and tools). In the statistical analysis several possible sources of bias as the frequency of the target word, the familiarity with the objects to name, the image complexity and other parameters were taken into account. Results – Four out of seven patients were significantly more impaired with living things. We describe their general cognitive profile and discuss the anatomo-functional aspects of category dissociation. Conclusion – Language impairment, disproportionately severe for the naming of living exemplars, is frequently observed in HSE, is clinically relevant and should be specifically investigated.     

Diagnosis of herpes simplex encephalitis

In a series of six cases of encephalitis caused by herpes simplex virus, type 1, the diagnostic and prognostic value of the electroencephalogram (EEG) was investigated. Special interest was focused on the time relationship between the appearance of abnormal EEG findings, the initial clinical symptoms and the changes in cranial computed tomography (CT). The characteristic periodic EEG pattern can be demonstrated within 2 days of disease, before typical structural changes appear in CT. A unilateral periodic pattern may be associated with a good prognosis, where-as all patients with bilateral changes died in spite of specific antiviral therapy.     

Murray valley encephalitis mimicking herpes simplex encephalitis.

We describe a patient with serologically proven Murray Valley encephalitis (MVE), whose presentation was clinically and radiologically characteristic of Herpes simplex encephalitis (HSE). The reports of MRI abnormalities in MVE, and the closely related Japanese Encephalitis and West Nile virusii are mostly of bilateral thalamic or grey matter involvement. The MRI scan findings in this case instead showed the typical temporal lobe changes of HSE. Our case report highlights that MVE can mimic HSE, both clinically and radiologically. Therefore it is important to collect an accurate and detailed travel history from patients where there is a risk of exposure to MVE virus. If suspected, antibody testing of serum and CSF, and CSF for MVE-RNA if available, should be undertaken. This case also highlights the potential under-diagnosis of Murray Valley encephalitis.     

LaCrosse viral encephalitis mimics herpes simplex viral encephalitis

Temporal lobe abnormalities, findings commonly associated with herpes simplex virus encephalitis, were observed in a male 10 years of age found to have LaCrosse virus encephalitis. Diagnostic features included magnetic resonance imaging revealing abnormal signal intensity in the bilateral frontotemporal regions, and left-sided periodic lateralizing epileptiform discharges. LaCrosse virus encephalitis should be included in the differential diagnosis of viral encephalitis associated with structural and electrographic temporal lobe lesions, represented by periodic lateralizing epileptiform discharges. The recently developed LaCrosse RNA polymerase chain reaction for cerebrospinal fluid may enable rapid diagnosis, prevent the need for treatment with acyclovir, and give parents an encouraging prognosis.     

Postinfectious immune-mediated encephalitis after pediatric herpes simplex encephalitis

We report a 3-year-old patient who presented a secondary acute neurological deterioration clinically characterized by a partial Kluver-Bucy syndrome, 1 month after the onset of herpes simplex encephalitis. This episode is unlikely due to continuation or resumption of cerebral viral replication but might be related to an immune-inflammatory process. In children, postinfectious immune-mediated encephalitis occurring after HSE are usually clinically characterized by choreoathetoid movements. This type of movement disorder was, however, not observed in this patient. On the basis of this case and a review of the literature, we hypothesize the existence of a spectrum of secondary immune-mediated process triggered by herpes simplex virus cerebral infection ranging from asymptomatic cases with diffuse white matter involvement to secondary acute neurological deteriorations with or without extrapyramidal features.