Acute Herpes Simplex Encephalitis Research Articles

Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence.

There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute to a better understanding of some of these mechanisms. We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria. All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic-ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%). Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release.

Nicotinamide n-Oxide Attenuates HSV-1-Induced Microglial Inflammation through Sirtuin-1/NF-κB Signaling.

HSV-1 is a typical neurotropic virus that infects the brain and causes keratitis, cold sores, and occasionally, acute herpes simplex encephalitis (HSE). The large amount of proinflammatory cytokines induced by HSV-1 infection is an important cause of neurotoxicity in the central nervous system (CNS). Microglia, as resident macrophages in CNS, are the first line of defense against neurotropic virus infection. Inhibiting the excessive production of inflammatory cytokines in overactivated microglia is a crucial strategy for the treatment of HSE. In the present study, we investigated the effect of nicotinamide n-oxide (NAMO), a metabolite mainly produced by gut microbe, on HSV-1-induced microglial inflammation and HSE. We found that NAMO significantly inhibits the production of cytokines induced by HSV-1 infection of microglia, such as IL-1β, IL-6, and TNF-α. In addition, NAMO promotes the transition of microglia from the pro-inflammatory M1 type to the anti-inflammatory M2 type. More detailed studies revealed that NAMO enhances the expression of Sirtuin-1 and its deacetylase enzymatic activity, which in turn deacetylates the p65 subunit to inhibit NF-κB signaling, resulting in reduced inflammatory response and ameliorated HSE pathology. Therefore, Sirtuin-1/NF-κB axis may be promising therapeutic targets against HSV-1 infection-related diseases including HSE.

Persistent inflammation and neuronal loss in the mouse brain induced by a modified form of attenuated herpes simplex virus type I

Herpes simplex virus-1 (HSV-1) is a widespread neurotropic virus that can reach the brain and cause a rare but acute herpes simplex encephalitis (HSE) with a high mortality rate. Most patients present with changes in neurological and behavioral status, and survivors suffer long-term neurological sequelae. To date, the pathogenesis leading to brain damage is still not well understood. HSV-1 induced encephalitis in the central nervous system (CNS) in animals are usually very diffuse and progressing rapidly, and mostly fatal, making the analysis difficult. Here, we established a mouse model of HSE via intracerebral inoculation of modified version of neural-attenuated strains of HSV-1 (deletion of ICP34.5 and inserting a strong promoter into the latency-associated transcript region), in which the LMR-αΔpA strain initiated moderate productive infection, leading to strong host immune and inflammatory response characterized by persistent microglia activation. This viral replication activity and prolonged inflammatory response activated signaling pathways in neuronal damage, amyloidosis, Alzheimer's disease, and neurodegeneration, eventually leading to neuronal loss and behavioral changes characterized by hypokinesia. Our study reveals detailed pathogenic processes and persistent inflammatory responses in the CNS and provides a controlled, mild and non-lethal HSE model for studying long-term neuronal injury and increased risk of neurodegenerative diseases due to HSV-1 infection.

Granulomatous Herpetic Encephalitis A Possible Role for Inflammasomes.

Granulomatous herpetic encephalitis is a rare inflammatory complication of acute herpes simplex encephalitis. We describe 3 cases of granulomatous herpetic encephalitis in children arising between 1 to 10 years after the initial presentation with acute herpes simplex encephalitis. We focus on the clinical course and neuroimaging phenotype with a discussion of possible mechanisms underpinning this entity. The clinical course was highly variable. However, the dominant neuroimaging phenotype in each of our cases was that of confluent gyriform cortical enhancement with predominantly solid foci of enhancement in the subjacent white matter +/- deep gray nuclei. Cerebrospinal fluid was negative for herpes simplex virus DNA in all cases. All 3 cases required brain biopsy to help establish the diagnosis. Increased recognition of granulomatous herpetic encephalitis in children will facilitate earlier diagnosis and treatment. Although the exact role played by the host immune response, genetics, and environment in determining the different outcomes of herpes simplex encephalitis remains to be determined, we postulate a role for inflammasome dysregulation in this entity.

HSV encephalitis after successful minimally invasive debridement for infected pancreatic necrosis: A case of rare central nervous system complication

Patients with acute pancreatitis (AP) often suffer tough complications, some of which are fatal. The early diagnosis and definite treatment of central nervous system (CNS) complications have not been fully achieved yet, which seriously affects the mortality of severe acute pancreatitis (SAP). We present a case of infected pancreatic necrosis (IPN) in a 62-year Chinese man who developed acute herpes simplex encephalitis (HSE) caused by herpes simplex virus type 1 (HSV-1) after favorable minimally invasive retroperitoneal approaches (MIRAs). The patient was successfully treated with 115 days stayed in our hospital. The MIRAs included image-guided retroperitoneal percutaneous catheter drainage (PCD), nephroscopic pancreatic necrosectomy (NPN), and ultrasonic pneumatic lithotripsy system (UPLS) assisted non-narcotic sinus track necrosectomy (NSN). HSE is relatively rare and potentially life threatening. We attempt to discuss the probable risk factors and how the relatively rare HSE are related to the patients of SAP with latent HSV.

Bioinformatics Review of the Role of HSV-1 in Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the progressive loss of cognitive functions in affected individuals. Brain tissue pathology is associated with the formation of senile plaques which result from the over-production of amyloid β (Aβ), due to the cleavage of a membrane bound glycoprotein. It is unclear what causes AD and its associated pathologies, but age and genetic predisposition play an import role in the likelihood of disease development. Studies have shown that the reactivation of latent herpes simplex virus 1 (HSV-1) infection can lead to the neuropathy of acute herpes simplex encephalitis (HSE), which causes similar symptoms to AD. HSV-1 infection is a known risk factor for the development of AD, but no study has determined a definitive causal relationship. Using the Qiagen Ingenuity Pathway Analysis (IPA) tool, the inhibitory relationship between therapeutics for AD and HSV-1 were explored. Thirteen drugs developed to decrease Aβ buildup in AD and 32 drugs that act as HSV antivirals were retrieved from the data in the Qiagen Knowledge Base. These drugs were analyzed displayed as two separate networks. While many promising Aβ aggregation-targeting drugs have been discontinued due to lack of efficacy, HSV drugs could serve as potential therapeutics for those with AD. This review aims to describe new insights on how HSV-1 relates to the development of AD and highlight the mechanism of action of Aβ-related drugs and HSV drugs in the context of AD. With HSV-1 being a likely candidate for the causation of AD, there is a need to study the effects of HSV antiviral drugs on those who have AD.

Transient naming deficits associated with insular lesions in a patient with encephalitis

ABSTRACTWe describe a patient with acute herpes simplex encephalitis with left-hemispheric hippocampal, parahippocampal and insular lesions. Although prototypic language areas were unaffected, the patient suffered from an inability to name objects or animals displayed on pictures. This deficit was transient and gradually disappeared 8 weeks after the initial diagnosis. Our findings are in line with a previous report showing similar deficits in a patient with a comparable lesion pattern and support the hypothesis that left insular lesions can produce severe naming deficits. Using FDG-PET we ruled out that functional deactivation in classical language areas account for the observed naming deficits.

Antiviral Therapy for Herpes Simplex Virus Encephalitis: Systematic Review and Meta Analysis of RCTs

Background: Herpes simplex virus (HSV) infection of the brain is treated with antiviral drugs like Acyclovir. A summary of randomized control trials of antiviral drugs against HSV encephalitis has not been put forward yet. Objectives: To determine the effect of antiviral agents in the treatment of HSV encephalitis on mortality and neurological sequelae at approximately two years. The secondary objective was to assess the adverse effect of antiviral agents on the patients. Search methods: Trials were identified by searching the PUBMED, European Medical Agency, USFDA, US Clinical trials, Elsevier database and Cochrane website and the reference lists of published trials. Selection criteria: Randomized controlled trials of antiviral therapy in biologically proven HSV infection was included. Main results: A total of 5 studies met the criteria. The first study was published in 1980 and the latest was in 2015. All the studies used acyclovir/valacyclovir or vidarabine. Three studies compared acyclovir and vidarabine, one study was placebo controlled vidarabine trial and another one was a placebo controlled trial of long term valacyclovir therapy. Acyclovir improved mortality and lowered the incidence of neurological sequelae. There was no significant reduction in the risk of mortality with vidarabine therapy. Authors' conclusions: Trial evidence suggests that acyclovir decreases mortality and morbidity in acute HSV encephalitis. Funding: None. Declaration of Interest: None.

Review of Viral Encephalitis Cases Seen at a Tertiary Care Center in Turkey: Focus on Herpes Simplex Type 1.

The objective of this study was to determine the incidence of herpes simplex encephalitis (HSE), known as the most common, potentially mortal, and treatable cause of sporadic encephalitis, in a sample Turkish population. The demographic, clinical, laboratory, imaging, electrophysiology, and polymerase chain reaction (PCR) DNA results of patients examined with a pre-diagnosis of encephalitis were retrospectively examined. A total of 68 patients were included in the study. The most common presenting symptom was altered behavior (67.6%), while temporal T2 hyperintensity was determined in the magnetic resonance imaging (MRI) of 27.9% of the patients and electroencephalography (EEG) abnormalities were determined in 66.2% of the patients. Lymphocytic pleocytosis was determined in the cerebrospinal fluid (CSF) in 35 patients. Fifty-seven patients had been diagnosed with viral encephalitis, 3 with bacterial meningitis, 3 with tuberculous meningitis, 2 with sporadic Creutzfeld-Jakob disease, 2 with acute disseminating encephalomyelitis, and 1 with Brucella encephalitis. Seven (10.2%) cases of viral encephalitis were found to be positive for herpes simplex virus (HSV) DNA by PCR. Viral encephalitis is the most common cause of infectious encephalitis; however, other atypical causes should also be noted. Negative PCR results for HSV DNA should not exclude the need for antiviral therapy in patients with a strong pre-diagnosis of HSE because diagnostic modalities, including PCR, may fail in acute settings and HSE remains the sole treatable cause of infectious encephalitis.

Herpes Simplex Encephalitis: an Update

The goal of this review is to provide an update on current thinking regarding herpes simplex encephalitis (HSE), emphasizing new information about pathogenesis, diagnosis, and immune responses. Specific questions to be addressed are the following: (1) Is there a genetic predisposition to HSE? (2) What clinical approaches have the greatest impact on improving the long-term outcomes in patients with HSE? And (3) are there immune-mediated mechanisms that may account for relapsing HSE? Toll-like receptor 3 (TLR 3) plays an important role in innate immune responses, including generation of interferons. Multiple single-gene errors in TLR 3 interferon pathways have recently been described in children that result in increased susceptibility to HSE. Conversely, studies in both animal models and humans indicate that both cytolytic viral replication and immune-mediated responses (including cytotoxic T lymphocytes and immune mechanisms mediated by TLR 2) contribute to the pathology of HSV, suggesting possible new therapeutic approaches. In terms of treatment, data clearly indicate that a longer duration between onset of symptoms and initiation of effective antiviral therapy correlates directly with less favorable clinical outcome. Recurrent or relapsing HSE may occasionally occur, but recent observations indicate that many instances of "relapsing HSE", especially in children, are more often anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis triggered by the antecedent HSV infection. Innate immune responses are critical for defense against HSV; genetic defects in this system may predispose patients to HSE. During acute HSE, exuberant immune responses may contribute to the CNS pathology, suggesting that selective immunosuppressive therapy, coupled with potent antiviral drugs, may eventually play a role in the therapeutic management of HSV. While overall clinical outcomes of HSE remain suboptimal, the initiation of high-dose acyclovir therapy as early as possible in the course of the illness provides the best chance for a patient to survive with minimal neurologic damage. Distinguishing relapsing HSE from autoimmune anti-NMDAR antibody encephalitis is critically important because therapeutic approaches will be very different.

A Feasibility Study of Quantifying Longitudinal Brain Changes in Herpes Simplex Virus (HSV) Encephalitis Using Magnetic Resonance Imaging (MRI) and Stereology.

ObjectivesTo assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid therapy.MethodsThe study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting.ResultsTemporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids.ConclusionsThis study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis.

Cranial CT/MRI findings in children with acute herpes simplex encephalitis

In this study, cranial computerized tomography (CT) and/or magnetic resonance imaging (MRI) findings were investigated in nine children with acute herpes simplex encephalitis (HSE). HSE was confirmed by polymerase chain reaction. Our purpose was to evaluate the diagnostic value of CT and MRI in the diagnosis of HSE and to determine the widespread of the cranial abnormalities in HSE in childhood. Cranial CT was examined in all children and found to be normal in four children. Cranial MRI was examined in seven children, of whom, three was normal. Temporal involvement was diagnosed in only two children. Our findings revealed that the range of cranial involvement was fairly variable in childhood HSE; aside from typical temporal involvement, cranial images may be normal or widespread involvement including basal ganglia, thalamus, frontal and parietal lobes may be seen in children with HSE.

Viral triggering of anti-NMDA receptor encephalitis in a child – An important cause for disease relapse

Herpes simplex encephalitis (HSE) in children is a potentially devastating condition which is occasionally complicated by a clinical relapse. An autoimmune component has long been suspected in these relapses and recent findings suggest that antibodies against N-methyl-d-aspartate receptors (NMDARs) may be part of this mechanism.We here report an 11 months old girl with acute HSE and with negative NMDAR antibody serology at presentation who after an initial response to antiviral treatment deteriorated with seizures, abnormal movements, focal neurologic deficits and psychiatric symptoms. We show that this relapse occurred as production of NMDAR antibodies developed and that clinical improvement followed immunotherapy with a concomitant decrease in NMDAR antibody titers in CSF. She also developed a characteristic 15–20 Hz activity over both hemispheres which has been previously described as an electroencephalographic presentation of anti-NMDAR encephalitis.We conclude that relapse or persisting symptoms in HSE in children may represent an immune-mediated mechanism rather than a viral reactivation and that NMDAR antibodies should be analyzed as this may be of importance for the choice of therapy.

The underlying aetiologies of coma in febrile Sudanese children

Cerebral malaria, acute bacterial meningitis and viral encephalitis are the main causes of fever and altered consciousness in the tropics. In areas where reliable laboratory testing is unavailable, over diagnosis and misdiagnosis of these conditions is likely. In malaria endemic countries non-malarial contributors to coma may be overlooked, overburdening available resources. The aim of this study is to evaluate the underlying causes of altered mental state in children presenting with fever and coma to tertiary medical facilities in Sudan. Children over one month of age admitted to the emergency departments of three main hospitals in Khartoum with fever and coma were investigated for cerebral malaria, acute bacterial meningitis and Herpes simplex encephalitis during April to November 2011. One hundred and four children presenting with fever and coma were evaluated. Cerebral malaria was clinically suspected in 38 patients and 5 were confirmed. Acute bacterial meningitis was suspected in 63 patients and confirmed in 15. Herpes encephalitis was confirmed in only one case. There were five cases of mixed infection and the remainder were unknown. The clinical diagnoses of cerebral malaria, acute bacterial meningitis and viral encephalitis are unreliable. Further studies to evaluate the underlying causes of coma in febrile Sudanese children are warranted.

Seizures and epilepsy in herpes simplex virus encephalitis: current concepts and future directions of pathogenesis and management

Mortality related to herpes simplex virus encephalitis (HSE) dropped dramatically with the systematic initiation of antiviral treatment in encephalitic syndromes. Further efforts need to be taken to reduce long-term morbidity in the survivors. In this regard, the high rate of postencephalitic epilepsy, which is frequently refractory to medical treatment, contributes significantly to the unfavorable clinical outcome of the disease. Seizures during the acute phase of HSE are the main risk for the development of postencephalitic epilepsy. Yet, there are no randomized controlled trials for the management of acute seizures, preventive measures or the ideal duration of antiepileptic treatment. Hence, concepts for the medical treatment of seizures during the acute phase of HSE and postencephalitic epilepsy are eagerly awaited. Epilepsy surgery is a potential treatment option for the latter, but only promising in a subgroup of patients suffering from unilateral mesio-temporal lobe epilepsy and congruent neuropsychological impairment. Relapsing HSE and post-infectious autoimmune conditions can lead to seizures in the aftermath of acute HSE. These conditions need to be kept in mind in order to promptly assure the initiation of accurate diagnostic steps and respective treatment. The purpose of this review is to summarize the current pathogenetical understanding, clinical and diagnostic considerations, and treatment options of seizures in acute HSE and postencephalitic epilepsy.

Epiglottoplasty for Dysphagia Associated Herpes Simplex Encephalitis

This report presents the case of a patient treated with epiglottoplasty (Biller's laryngoplasty technique) for the pseudobulbar type of dysphagia associated with herpes simplex encephalitis (HSE). A 67-year-old man developed acute HSE with disturbance of consciousness and intractable aspiration. Oral intake was tried, but resulted in aspiration pneumonia and was therefore canceled at the patient's former institution. At 12 months following onset, the patient consulted our hospital and we judged that aspiration could not be controlled, and that surgical management would be needed. In order to both prevent aspiration and preserve phonation, epiglottoplasty was performed at 15 months following onset. Postoperatively, the patient was able to resume an unrestricted diet except for clear liquids. He also underwent voice rehabilitation with the support of his family and rehabilitation staff. These efforts finally enabled him to speak clearly. Epiglottoplasty is an effective treatment for intractable aspiration, but this procedure is not widely known to Japanese physiatrists. Careful patient screening and selection by the attending physiatrist is essential, as is providing adequate postoperative swallowing and voice rehabilitation.

Herpes Encephalitis Presenting With an Opercular Syndrome and Epilepsia Partialis Continua

The opercular syndrome is a rare form of pseudobulbar palsy that is characterized by automatic-voluntary dissociative weakness of the face in addition to weak masticatory and pharyngeal muscles. It is typically seen in the setting of an acute stroke or in association with various congenital malformations of the cortex. It has also been described rarely in association with herpes encephalitis but with an abnormal cerebrospinal fluid (CSF) cell count. We report on a 65-year-old-man with an opercular syndrome associated with epilepsia partialis continua (EPC) secondary to acute herpes simplex virus encephalitis despite an initial near normal CSF analysis. Initial EEG was unremarkable while CSF analysis revealed changes suggestive of a traumatic tap. An opercular syndrome was diagnosed based on the classic presentation of dysarthria, facial diplegia, and hypersalivation, with corresponding MRI brain changes in the operculum. During admission, EPC developed, with continuous right facial twitching and an electroencephalographic correlate in the left centrotemporal region. The EPC initially responded to intravenous lorazepam. Phenytoin was then added for seizure prophylaxis. Herpes virus DNA was later on detected in the CSF. The patient improved with antiviral treatment except for very mild residual dysarthria. Neurologists should be aware of the possible predilection of the herpes simplex virus for the opercular area and the need to empirically treat for herpes encephalitis even in the setting of near normal initial CSF studies in patients with a suggestive clinical presentation.

Herpes simplex encephalitis: A serological follow-up study

A solid-phase radioimmunoassay method was used for the detection of herpes simplex virus (HSV) immunoglobulin M (IgM), IgA, and IgG antibodies within the central nervous system in 11 patients with acute HSV encephalitis. Serial cerebrospinal fluid (CSF) and serum specimens were sampled during the observation periods, extending up to 43 months after onset. The clinical diagnosis of HSV encephalitis was confirmed demonstrating virus or virus antigen in the central nervous system in four patients and with significant HSV antibodies in CSF in all the patients. In acute stage CSF HSV antibodies of a significant level were demonstrated in one of four samples taken on days 3--4 after onset, and in samples taken on days 6--8 in five of nine patients. CSF HSV antibodies of a significant and high level were detected in all samples taken from day 10 after onset. Intrathecal production of HSV IgM and IgA antibodies lasted from 7 weeks to 43 months during the observation periods. All patients had persistent intrathecal production of HSV IgG antibodies as well as of oligoclonal IgG during the total observation periods up to 43 months.

Acute herpes simplex encephalitis: clinical assessment and prognostic data.

Acute herpes simplex encephalitis (HSE) has a grave outcome, and detection of prognostic features is of clinical importance. Thirty patients with HSE were assessed in a retrospective study. Diagnosis was confirmed by serological methods using the indirect immunofluorescence technique (IFT). Antiviral treatment was given to 23 of the patients. Focal convulsions were more frequent in patients below 18 years of age, while confusion and memory disturbances were prevalent among patients above 18. The final outcome was influenced by the degree of severity of the disease at the peak and the state of consciousness and duration of disease prior to the initiation of anti-viral treatment. No correlation was found between antibody levels in serum or in CSF and the outcome. We conclude that the clinical degree of severity the duration of illness prior to treatment and state of consciousness at the initiation of anti-viral treatment are of prognostic importance.

Evaluation of Auditory Brainstem Potentials in Children with Acute Herpes Simplex Encephalitis

Objective: In this study, auditory brainstem potentials (ABPs) were studied in children with Herpes simplex encephalitis (HSE) to determine the ABP abnormalities in HSE during childhood. We also wished to determine whether or not to use ABP in early diagnosis of HSE. Method: The study includes 28 children; eight children with acute HSE, nine with nonspecific encephalitis, and 11 healthy age-matched control subjects. The diagnosis of HSE was confirmed by the demonstration of Herpes simplex virus type 1 in CSF by polymerase chain reaction. Recordings of ABPs were performed by using Nihon Kohden Neuropack 2 device. Results: The study includes eight children (four females and four males) with acute HSE, nine children (five males and four females) with nonspecific encephalitis, and 11 healthy age-matched control subjects (six males and five females). Age ranges of the patients and controls were between six months and 12 years. There was not statistically significant difference between the groups for age and gender (p > .05). There were significant differences in the mean latencies of the wave IV on the right ear and in the mean interpeak latencies (IPLs) of the waves III–V on the right and left ears between the nonspecific encephalitis group and the control group (p < .05). However, there were no statistically significant differences between the HSV and control groups (p > .05). In addition, there was no significant difference between HSV and nonspecific groups (p > .05). Conclusions: Our findings revealed that there were mild ABP abnormalities in children with nonspecific encephalitis, but no ABP abnormality in patients with HSV encephalitis. However, we think that more extensive and detailed studies should be performed to determine whether or not there were ABP abnormalities in childhood HSV encephalitis.