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Purpose: Herpes simplex virus (HSV) encephalitis continues to be the most common form of sporadic lethal encephalitis worldwide. The wide spectrum of clinical presentations and laboratory findings often poses a diagnostic challenge for physicians which might delay administration of life-saving therapy with acyclovir. Atypical presentations of HSV encephalitis have become increasingly prevalent with better diagnostic techniques and have not been well studied., Methods: We retrospectively evaluated all consecutive PCR-proven HSV encephalitis cases treated at the Hospital of the Ludwig-Maximilians-University in Munich, Germany from January 1, 2013 to February 28, 2018., Results: We included 18 patients with PCR-proven HSV encephalitis. The most common clinical features were altered mental status (77.8%), focal neurologic deficits (72.2%) and fever (72.2%). Remarkably, four of these patients (22.2%) had a normocellular cerebrospinal fluid (CSF) on admission. Electroencephalography and magnetic resonance imaging abnormalities were highly sensitive for HSV encephalitis independent of CSF cell count. Striking atypical findings on MRI were extensive global brain swelling and severe brainstem involvement in single patients. Of note, initial CT scans were normal in 11 out of 16 patients (68.8%). All patients were treated with acyclovir. Three patients still developed a clinical deterioration under therapy with acyclovir with one patient requiring decompressive craniotomy due to bilateral space-occupying temporal lobe hemorrhage. 94.4% of the patients survived but only 38.9% were discharged with a good clinical outcome (Glasgow Outcome Score = 5)., Conclusion: Atypical presentations of HSV encephalitis seem to be more common than previously thought and physicians should apply a high level of clinical suspicion and a low threshold to initiate life-saving acyclovir therapy in suspected cases.

We compared the clinical course of neonates with persistence of herpes simplex virus (HSV) deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF) after 21 days of treatment with high-dose acyclovir to that of neonates with clearance of the CSF after 21 days of therapy. Neonates with persistence of HSV DNA had a more severe clinical course with worse neurodevelopmental outcomes.

Genital herpes simplex virus (HSV) infections are very common worldwide. Approximately 22% of pregnant women are infected genitally with HSV, and most of them are unaware of this. The most devastating consequence of maternal genital herpes is HSV disease in the newborn. Although neonatal HSV infections remain uncommon, due to the significant morbidity and mortality associated with the infection, HSV infection in the newborn is often considered in the differential diagnosis of ill neonates. This review summarizes the epidemiology and management of neonatal HSV infections and discusses strategies to prevent HSV infection in the newborn., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Acyclovir (ACV), which inhibits the replication of herpes simplex virus, is the standard drug for the treatment of herpes simplex encephalitis. Thanks to the introduction of ACV, the morbidity and mortality of HSE patients have significantly improved. However, the disease is still the severe infection, because it makes some patients with HSE suffer from severe consequences. The sensitivity test of the etiological HSV to ACV is very difficult due to the inability of isolation of the virus from cerebrospinal fluid (CSF). The cases of the ACV treatment-resistant HSE patients have been reported. However, these cases were not virologically confirmed. The first case of encephalitis in newborn baby with HSE caused by an ACV-resistant HSV-1, which was virologically confirmed, was reported by our group. According to the sensitivity profile of the causative viruses to antiviral drugs, the drugs of choice for HSE should be properly considered. Strategy for diagnoses of HSE including antiviral sensitivity assessment and selection of drugs in HSE is reviewed.

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.

Background: Diagnosis of herpes simplex encephalitis (HSE) is based on clinical findings, MRI, and detection of herpes simplex virus (HSV) DNA in cerebrospinal fluid (CSF) using polymerase chain reaction amplification. Delays in starting treatment are associated with poorer clinical outcomes. We assessed the timing of initiation of acyclovir therapy in HSE., Methods: Inpatient databases from seven hospitals in Winnipeg, Manitoba were used to identify individuals diagnosed with encephalitis and HSE from 2004 to 2009. The time taken to initiate therapy with acyclovir and the reasons for delays were determined., Results: Seventy-seven patients were identified; 69 (90%) received acyclovir; in the others a non-HSV infection was strongly suspected. Thirteen patients were subsequently confirmed to have HSE. Acyclovir was initiated a median of 21 hours (3-407) after presentation in encephalitis cases, and a median of 11 hours (3-118) in HSE. The most common reason for delay was a failure to consider HSE in the differential diagnosis, despite suggestive clinical features. Where therapy was delayed in HSE patients, the decision to begin acyclovir was prompted by transfer of the patient to a different service (55%), recommendations by consultants (18%), imaging results (18%), and CSF pleocytosis (9%)., Conclusions: Delays in initiating acyclovir for HSE are common, and are most often due to a failure to consider HSE in a timely fashion on presentation. In order to improve patient outcomes, physicians should be more vigilant for HSE, and begin acyclovir therapy expeditiously on the basis of clinical suspicion rather than waiting for confirmatory tests.

This study reports on the clinical profiles of herpes simplex encephalitis (HSE) case-patients and the management of acyclovir prescriptions. We designed a study on the causes of encephalitis in France in 2007. Case-patients fulfilling the inclusion criteria were enrolled in all the hospitals that volunteered to participate. Fifty-five of 253 enrolled case-patients were diagnosed with HSE. Three (5%) HSE patients died and 48 (89%) were discharged with persistent neurological symptoms. All HSE patients were prescribed acyclovir, 10 of whom had a 2-week course; 42 a 3-week course; two received incomplete courses; and one received two courses of 21 days each due to relapse. The acyclovir dosage was reported for 45 adult HSE patients, 25 (53%) of whom received 10 mg/kg t.i.d. and 22 (47%) received 15 mg/kg t.i.d. The mortality rate was low despite 49% of patients being admitted to intensive-care units. A high dose of acyclovir was not associated with a better outcome in HSE patients. Most patients had persisting symptoms on discharge suggesting neuropsychological rehabilitation is an important issue for survivors.

Objective: The significance of detecting herpes simplex virus (HSV) DNA in the cerebrospinal fluid (CSF) of infants with HSV encephalitis after receipt of prolonged therapy with high-dose (60 mg kg(-1) day(-1)) acyclovir is unknown. We report the clinical and laboratory characteristics, neuroimaging studies and outcomes of four neonates with HSV encephalitis who had persistence of CSF HSV DNA, by polymerase chain reaction (PCR) after 15 to 21 days of high-dose acyclovir therapy., Study Design: Retrospective chart review., Results: All four infants had abnormal neuroimaging studies and subsequently experienced severe developmental delay or death., Conclusion: A persistently positive CSF HSV PCR in neonates may be another risk factor for worse neurodevelopmental outcome. Prospective studies are needed to document how often HSV DNA persists in CSF, elucidate whether it represents an initially high CSF viral load, ongoing viral replication or viral resistance, and determine its possible association with neurodevelopmental impairment.

In spite of high rates of morbidity and mortality in herpes simplex virus (HSV) encephalitis, however, it is one of the exceptional viral infections with specific and effective therapy. In this report a HSV encephalitis case who was clinically unresponsive to acyclovir treatment, has been presented. An 11 months old girl patient has been brought to our clinic with the complaints of high fever and focal convulsions. Analysis of cerebrospinal fluid (CSF) revealed decreased glucose level and abundant red blood cells, despite it was not traumatic. The other CSF biochemical findings were found normal. Viral serology performed with CSF yielded negative result for HSV-1 IgG, positive result for HSV-2 IgG, and negative result for HSV-1/2 IgM, however, antibody index could not be estimated since it was not possible to obtain a simultaneous serum sample. Cranial magnetic resonance imaging (MRI) showed contrast material enhancement on bilateral temporal lobes. There was no growth in the CSF cultures. Acyclovir therapy (30mg/kg/day) was started with the prediagnosis of herpes encephalitis. In the third week of therapy CSF analysis was repeated because of the presence of partial paroxysmal attacts and absence of sufficient clinical improvement. In this CSF sample HSV-1 DNA was found positive by real-time polymerase chain reaction. Since CSF findings were still abnormal and the clinical picture worsened despite 21 days of therapy, the dose of acyclovir was increased to 60 mg/kg/day (3 weeks) with a possible drug resistance problem. Control brain MRI showed contrast enhancement on bilateral temporal lobes, with more intensivity in left, and encephalomalacia. Valproic acid and haloperidol were given to the patient for the treatment of permanent partial paroxysms and orofacial dyskinesis, developing in the follow-up period, respectively. After getting these complications under control, the patient was discharged and taken into follow-up. As a result, although it could not be possible to confirm the drug resistance by molecular methods, it was thought that this might be both a clinical and virological resistance phenomenon, because of the detection of HSV-DNA in the CSF sample during the period of severity of the illness.