acyclovir and Encephalitis--Herpes-Simplex

Herpes simplex virus (HSV) is a common cause of viral encephalitis and can result in refractory seizures. Although HSV encephalitis (HSVE) is treated primarily with acyclovir, surgery can play a role in medically intractable cases.. To systematically review cases describing surgery for the treatment of severe HSVE. We also present an illustrative case of anterior temporal lobectomy (ATL) for refractory status epilepticus in a patient with unilateral HSVE. This case demonstrates one clinical context in which surgery can be a useful adjunct.. We performed a systematic review using PubMed and Google Scholar, including case reports and series describing surgical interventions for HSVE. Clinical data were extracted from 54 publications that incorporated 67 patient cases.. Surgical decompression occurred at a wide range of times after the onset of illness, although most patients were operated on 4 or more days after HSVE symptoms began. Numerous reports indicated that decompressive craniectomy, temporal lobectomy, and hematoma removal could treat intractably elevated intracranial pressure because of HSVE with favorable long-term outcomes. We describe an additional case in which a 52-year-old woman with HSVE developed refractory right temporal lobe seizures. After ATL, the seizures resolved with significant clinical improvement.. Surgical treatment can be a useful adjunct for treatment of HSVE. There is substantial variability in the timing of surgical decompression in patients with HSVE, which can be necessary up to approximately 3 weeks after illness onset. ATL should be considered for refractory status epilepticus in HSVE with a unilateral seizure focus.

Topics: Acyclovir; Anterior Temporal Lobectomy; Encephalitis, Herpes Simplex; Female; Humans; Middle Aged; Seizures; Status Epilepticus

Herpes simplex virus encephalitis (HSVE) is one of the most common infectious causes of sporadic encephalitis. Coronavirus disease (COVID-19) has been associated with immune dysregulation of the host that might increase the risk of infections like HSVE following SARS-CoV-2 infection. There is paucity of literature on post COVID-19 HSVE. This study was conducted with the aim of analyzing the clinical presentation, brain imaging, and outcome of patients presenting with HSVE within 6 weeks of COVID-19 and providing a comprehensive review on the possible mechanisms of post-COVID-19 HSVE.. This observational study included patients who had laboratory-confirmed HSVE (type 1 or type 2) and a history of COVID-19 within the previous 6 weeks. Patients were followed up for 3 months.. Eight patients were included and all of them had type 1 HSVE. The mean latency of onset of neurological symptoms from being diagnosed with COVID-19 is 23.87 days and a majority of the patients have received injectable steroids with a mean duration of 6.5 days. Behavioral abnormality was the commonest neurological presentation and typical brain imaging involved T2 FLAIR hyperintensities of the medial temporal lobes. All patients received intravenous acyclovir 10 mg/kg every eight hourly for atleast 14 days. One patient with concomitant rhinocerebral mucormycosis succumbed while the majority had a complete recovery.. Possible immune dysregulation in COVID-19 may increase the susceptibility of HSVE in patients with a history of recent SARS-CoV-2 infection. The clinical manifestations and laboratory findings of HSVE in such patients are similar to typical HSVE.

Topics: Acyclovir; COVID-19; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Observational Studies as Topic; SARS-CoV-2

The typical herpes simplex viral encephalitis (HSVE) course is an acute illness, less commonly it may present as a chronic course, mainly in children, and rarely may it be subacute. Subacute HSVE is rarely described in the literature being reported 4 times only.. We here report 2 cases of subacute HSV1 encephalitis diagnosed based on cerebrospinal fluid polymerase chain reaction and magnetic resonance imaging findings and review the literature trying to find any specific clinical, laboratory, radiologic diagnostic or prognostic criteria regarding this subacute form of HSVE.. There is subacute form of HSVE and should be suspected with any subacute febrile illness with nonspecific cognitive impairment even in the absence of focal neurological symptoms and in cases with rapidly progressive dementia. This form has similar radiologic finding and good response to acyclovir but carry even better prognosis than that the acute HSVE.

Topics: Acyclovir; Child; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Magnetic Resonance Imaging; Polymerase Chain Reaction

BACKGROUND Several cases of herpes simplex virus type 1 meningoencephalitis (HSVE) have been reported in patients receiving steroids, but the exact contribution of steroids to the disorder remains unclear because other risk factors, such as chemotherapy, brain radiation, or surgery, were present in almost all cases. CASE REPORT We report the case of a 76-year-old man who developed HSVE following the administration of pulse-dose steroids. The patient had occupational asbestos exposure and a chronic interstitial lung disease of unclear etiology (sarcoidosis versus hypersensitivity pneumonitis) and was admitted for acute-on-chronic respiratory failure requiring mechanical ventilation. After a negative infectious workup and several days of antibiotics without improvement, pulse-dose steroids were administered. In the following days, the patient developed a fever and worsening encephalopathy. A lumbar puncture showed elevated nucleated cells and positive polymerase chain reaction for herpes simplex virus 1 in the cerebrospinal fluid, confirming the diagnosis of HSVE. Acyclovir treatment was initiated, but the patient later died as a result of persistent severe encephalopathy and respiratory failure with an inability to wean mechanical ventilation. CONCLUSIONS Clinicians should keep in mind that HSVE is a potential complication of steroids and carefully consider the benefit/risk ratio of pulse-dose steroids, taking into account associated factors of immunosuppression. A high level of awareness should be especially maintained in critically ill patients because of associated risk factors (critical illness immune paralysis) and because neurological signs of HSVE may be missed in mechanically ventilated, sedated patients.

Topics: Acyclovir; Aged; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Meningoencephalitis; Methylprednisolone

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (AE) is a common cause of nonviral infectious encephalitis, which can be triggered by herpes simplex virus infection. Previous studies have shown that approximately 27% of herpes simplex encephalitis (HSE) patients produce anti-NMDAR antibodies within 3 months. Immunotherapy is recommended in this situation, but some symptoms usually remain in the 1-year follow-up.. A previously healthy 23-year-old Chinese young woman developed epileptic attack followed by psychiatric symptoms of confusion and irritation as well as cognitive deficits. Brain MRI showed hyperintense lesions of the right temporal lobe on DWI and T2 without contrast enhancement effects. Twenty-one days of acyclovir was administered based on the primary diagnosis of HSE. The anti-NMDAR antibody (IgG) was detected positively on day 11 after disease onset. She had improved cognitive function but suffered another grand mal epilepsy after the first course of intravenous immunoglobulin (IVIG) therapy combined with 1000 mg intravenous methylprednisolone. After discussion, another course of IVIG was started for 5 days. Her symptoms were well controlled with only mild cognitive deficits at the 1-year follow-up (mRS = 1).. Our case indicated that anti-NMDAR antibodies could develop earlier after HSE compared with previous data from adults. We suggested detecting AE antibodies simultaneously with each CSF analysis. Meanwhile, the second course of IVIG therapy was reasonable when symptoms were not controlled after the first course of IVIG combined with IV steroid treatment.

Topics: Acyclovir; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Encephalitis, Herpes Simplex; Female; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Receptors, N-Methyl-D-Aspartate; Young Adult

Acyclovir is an antiviral drug poorly absorbed in the gastrointestinal tract due to its hydrophilicity, with low oral bioavailability (~20%). Although acyclovir is prescribed in the management of herpes simplex encephalitis (HSE), the disease has a poor prognosis, particularly if the treatment is delayed, reaching mortality rates of 70% if left untreated. Thus, high acyclovir doses are administered by intravenous (IV) infusion, usually at a dosage of 10 mg kg

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Infusions, Intravenous; Prodrugs

Herpes simplex virus 1 (HSV-1) can be responsible for life-threatening HSV encephalitis (HSE). The mortality rate of patients with HSE who do not receive antiviral treatment is 70%, with most survivors suffering from permanent neurological sequelae. The use of intravenous acyclovir together with improved diagnostic technologies such as PCR and magnetic resonance imaging has resulted in a reduction in the mortality rate to close to 20%. However, 70% of surviving patients still do not recover complete neurological functions. Thus, there is an urgent need to develop more effective treatments for a better clinical outcome. It is well recognized that cerebral damage resulting from HSE is caused by viral replication together with an overzealous inflammatory response. Both of these processes constitute potential targets for the development of innovative therapies against HSE. In this review, we discuss recent progress in therapy that may be used to ameliorate the outcome of patients with HSE, with a particular emphasis on immunomodulatory agents. Ideally, the administration of adjunctive immunomodulatory drugs should be initiated during the rise of the inflammatory response, and its duration should be limited in time to reduce undesired effects. This critical time frame should be optimized by the identification of reliable biomarkers of inflammation.

Topics: Acyclovir; Adrenal Cortex Hormones; Animals; Antiviral Agents; Drug Therapy; Encephalitis, Herpes Simplex; Genetic Predisposition to Disease; Humans; Immunity; Immunomodulation; Risk Factors; Simplexvirus; Treatment Outcome

Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic viral encephalitis in children and is responsible for epilepsy in approximately half of patients. In addition to medical treatment, epilepsy surgery may be offered to drug-resistant patients but carries a high risk of relapse of herpetic encephalitis. We are reporting our series of patients operated on between 2000 and 2019 with the systematic administration of acyclovir (ACV).. Four pediatric patients aged 4.5-12.8 years with drug-resistant epilepsy post-HSE underwent a tailored focal resection following invasive recordings (three patients) and a complete callosotomy (one patient). The total number of the surgical procedures for the four patients was eight, and a systematic administration of ACV as a prophylactic treatment of herpetic encephalitis relapse was done at each step. No patients had a relapse and the ACV was well-tolerated in all the cases. Following surgery two patients are seizure free, the patient who underwent callosotomy is Engel 3 and the fourth patient, in whom a large epileptic zone has contraindicated a second surgery, is Engel 4.. Our series demonstrated the dramatic efficacy of systematic ACV prophylaxis during all cranial surgeries. Moreover, our results on epilepsy, together with those of the literature, encourage more consideration regarding epilepsy surgery in this specific etiology. All types of surgical procedures (curative or palliative) can be offered to the patients, but in the case of focal surgery, due to the poor anatomical limits, invasive recordings are highly recommended.

Topics: Acyclovir; Adolescent; Antiviral Agents; Child; Child, Preschool; Drug Resistant Epilepsy; Encephalitis, Herpes Simplex; Epilepsy; Female; Humans; Male; Secondary Prevention

Viral meningitis may be present not only in adults but also in children. It constitutes a significant public health problem in child population. The clinical manifestation of the disease in children varies depending on the age of the child, the causative agent or the way of acquiring the infection. Thanks to the widespread availability of vaccinations, the epidemiology of central nervous system infections is changing. The methods of diagnosing and determining the causative factor have also changed. Sensitive and rapid molecular methods such as PCR tests are being used more frequently. The article contains an overview of the most common causes, clinical signs and symptoms, complications and principles of diagnosing and treating viral meningitis in children. Currently, Enteroviruses are at the top positions among the causes of sporadic and epidemic meningitis in children living in various geographic regions of the world. In European countries, the common cause of viral meningitis and/or encephalitis is tick-borne encephalitis virus. The severity of the clinical course of TBE is inversely proportional to the age of the affected children. In USA, sub-Saharan Africa and recently in southern Europe epidemic West Nile Virus (Flaviviridae family) central system infections were reported. Herpes simplex encephalitis is uncommon in children and has a severe course (especially in vertically infected infants). The mortality rate in Herpes simplex encephalitis is 20- 25% despite acyclovir treatment.

Topics: Acyclovir; Child; Communicable Diseases; Encephalitis; Encephalitis Viruses, Tick-Borne; Encephalitis, Herpes Simplex; Europe; Humans; Infant

HSV is the most frequently identified cause of infectious encephalitis, in Western countries. This article is an update on the topic based on a review of recent studies from 2017 to 2018.. Acyclovir is still the first line treatment, and no new drugs are currently available for clinical use. The major considerations for HSV encephalitis are as follows: point one, clinical evaluation remains the most important factor, as though CSF HSV PCR has a good sensitivity, in a small proportion of patients the initial testing might be negative. MRI brain is the first line imaging test, and mesial temporal lobe involvement and other typical findings are important for diagnosis; point 2, there should be emphasis on sequela, short-term, and long-term outcomes, and not just case fatality rated in future studies and clinical management. Auto-immune encephalitis can be triggered by HSV, and should be considered in patients who are not responding to treatment; point 3, future studies should be on better management of sequela, and better treatment regimens including those targeting the immune response.. Autoimmune encephalitis is a clearly identified complication of HSV encephalitis. Inflammatory mechanisms are linked to the clinical presentation as well as severity and poor outcome. Initial corticosteroid therapy has to be evaluated in order to prevent complications.

Topics: Acyclovir; Antiviral Agents; Brain; Cerebrospinal Fluid; Diagnostic Tests, Routine; Disease Management; Encephalitis, Herpes Simplex; Humans; Magnetic Resonance Imaging; Molecular Diagnostic Techniques; Simplexvirus

Clinical researches indicate that acyclovir can be used to herpes simplex encephalitis (HSE). However, no systematic review has explored its efficacy for the treatment of HSE. Therefore, this study systematically will investigate the efficacy and safety of acyclovir for patients with HSE.. We will search the following databases from inceptions to March 1, 2019 without any language restrictions: Cochrane Library, Embase, MEDICINE, PsycINFO, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. This study will include randomized controlled trials that assess the efficacy and safety of acyclovir for patients with HSE. Two authors will independently carry out the study selection, data extraction, and risk of bias assessment. Cochrane risk of bias tool will be used to assess the risk of bias assessment.. This study will systematically assess the efficacy and safety of acyclovir for HSE. The primary outcome is mortality rate, which is measured by Glasgow coma score, or other instruments. The secondary outcomes include quality of life, as assessed by 36-Item Short Form Health Survey or relevant scales; overall survival, the number of patient who died; the number of patient who had severe sequelae, and adverse events.. The findings of this study may provide the existing evidence on the efficacy and safety of acyclovir for HSE.. PROSPERO CRD42019125999.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Humans; Randomized Controlled Trials as Topic; Research Design

Herpes simplex virus encephalitis (HSE) is the most common cause of letal encephalitis and its prevalence appears higher among oncologic patients who undergo brain radiotherapy (RT). We describe a case of 76-year-old woman with glioblastoma multiforme (GBM) who developed HSE shortly after brain RT. Cerebrospinal fluid analysis (CSF) was normal and the diagnosis was driven by brain MRI and EEG. Prompt introduction of antiviral therapy improved the clinical picture. We highlight the importance of EEG and brain MRI for the diagnosis and suggest the possibility of antiviral profilaxys in oncologic patients who undergo brain RT.

Topics: Acyclovir; Aged; Brain Neoplasms; Cranial Irradiation; Electroencephalography; Encephalitis, Herpes Simplex; Female; Glioblastoma; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Prognosis; Risk Assessment; Treatment Outcome

Acute hemorrhagic leukoencephalitis (AHL) is a rare and mostly fatal fulminant demyelinating disease. This case describes a 63-year old male in status epilepticus associated with an intracerebral hemorrhage following a one week viral prodrome with rapid decline to coma. He exhibited peripheral leukocytosis, neutrophilic pleocytosis with normal glucose and high protein in cerebrospinal fluid (CSF). Additionally, CSF was positive for herpes simplex virus (HSV) polymerase chain reaction (PCR). Medical decompression, low-dose dexamethasone, antibiotics and acyclovir were initially given. Magnetic resonance imaging (MRI) was suggestive of AHL, thus he was treated with methylprednisolone 1 g/day for 5 days. The patient improved and was discharged with significant neurologic morbidity. This is the first reported case of AHL in the Philippines presenting as a diagnostic dilemma with a protracted clinical course who responded to high dose intravenous steroids.

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; Encephalitis, Herpes Simplex; Humans; Leukoencephalitis, Acute Hemorrhagic; Male; Methylprednisolone; Middle Aged; Neuroprotective Agents; Status Epilepticus

Neonatal herpes simplex virus (HSV) is an uncommon but devastating infection in the newborn, associated with significant morbidity and mortality. The use of PCR for identification of infected infants and acyclovir for treatment has significantly improved the prognosis for affected infants. The subsequent use of suppressive therapy with oral acyclovir following completion of parenteral treatment of acute disease has further enhanced the long-term prognosis for these infants. This review article will discuss the epidemiology, risk factors and routes of acquisition, clinical presentation, and evaluation of an infant suspected to have the infection, and treatment of proven neonatal HSV disease.

Topics: Acyclovir; Antiviral Agents; Cesarean Section; Delivery, Obstetric; Disseminated Intravascular Coagulation; Encephalitis, Herpes Simplex; Extraction, Obstetrical; Extraembryonic Membranes; Female; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Keratitis, Herpetic; Labor, Obstetric; Liver Failure; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Respiratory Insufficiency; Risk Factors; Skin Diseases, Viral; Time Factors

Topics: Acute Disease; Acyclovir; Antiviral Agents; Brain; Encephalitis, Herpes Simplex; Encephalitis, Viral; Humans; Magnetic Resonance Imaging; Polymerase Chain Reaction

A 55-year-old man was admitted to our hospital for investigation of high fever, decreased consciousness and bilateral visual impairment. His cerebrospinal fluid analysis revealed pleocytosis of mononuclear cells and an increased protein concentration. FLAIR images revealed multiple high-intensity lesions in the frontal lobe, part of which was enhanced with gadolinium. Despite initiating treatment with acyclovir and corticosteroids, his consciousness and visual acuity deteriorated. Immunopathological examination of brain biopsies showed numerous herpes simplex virus type 2-positive neurons and macrophages, leading to a diagnosis of herpes simplex encephalitis (HSE). Fundoscopic examination revealed multiple foci of retinitis with vasculopathies, and inflammation in the anterior chamber and vitreous, indicating acute retinal necrosis (ARN). Foscarnet treatment was initiated in place of acyclovir and his consciousness improved, with a slight improvement in visual acuity. ARN is typically caused by a herpes virus infection limited to the eyeball, and rarely in combination with HSE. In such cases, there is a latency of approximately 2-4 weeks between ARN and the onset of encephalitis. Our case is unique in that HSE and ARN developed simultaneously, and it highlights that there may not always be a latency between the onsets of the two disorders. Finally, foscarnet should be considered in cases of HSE and ARN with acyclovir resistance.

Topics: Acute Disease; Acyclovir; Antiviral Agents; Disease Progression; Drug Resistance, Viral; Encephalitis, Herpes Simplex; Foscarnet; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Retinal Necrosis Syndrome, Acute; Treatment Failure; Treatment Outcome

Herpes simplex virus (HSV) encephalitis is uncommon in clinical practice, but is frequently suspected in patients with acute alterations of consciousness. Symptoms and physical signs are nonspecific, and diagnostic confirmation typically hinges on demonstration of viral DNA in cerebrospinal fluid. Brain MRI is helpful in diagnosis and provides prognostic information. Early initiation of intravenous acyclovir is essential to optimize the patient's chances of favorable recovery. HSV encephalitis can trigger an autoimmune reaction with the possible appearance of antibodies to neuronal surface antigens. Thus, recrudescence of neurologic impairment after a treated episode of HSV encephalitis warrants consideration of secondary autoimmune encephalitis.

Topics: Acyclovir; Adult; Antiviral Agents; DNA, Viral; Encephalitis, Herpes Simplex; Female; Humans

We report three cases of patients with developmental-delay from neonatal herpetic encephalitis and/or meningitis who presented years later with acute retinal necrosis due to herpes simplex virus. The diagnosis was delayed in all cases due to the patients' inability to verbalize their ocular complaints and cooperate with eye examinations. This case series documents the clinical course, pathophysiologic mechanism, and treatment of acute retinal necrosis in this patient population. Clinicians should understand the importance of prudent consideration of acute retinal necrosis in patients with a history of neonatal herpetic encephalitis and/or meningitis presenting with a red eye.

Topics: Acyclovir; Adult; Antibodies, Viral; Antiviral Agents; Child; Developmental Disabilities; DNA, Viral; Drug Combinations; Encephalitis, Herpes Simplex; Eye Infections, Viral; Glucocorticoids; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute; Simplexvirus; Virus Activation; Vitreous Body

Viral infections in the fetus or newborn often involve the central nervous system (CNS) and can lead to significant morbidity and mortality. Substantial progress has been made in identifying interventions decreasing adverse neurodevelopmental outcomes in this population. This review highlights progress in treatment of important viruses affecting the CNS in these susceptible hosts, focusing on herpes simplex virus (HSV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), and enteroviruses. The observation that high-dose acyclovir improves mortality in neonatal HSV disease culminated decades of antiviral research for this disease. More recently, prolonged oral acyclovir was found to improve neurologic morbidity after neonatal HSV encephalitis. Ganciclovir, and more recently its oral prodrug valganciclovir, is effective in improving hearing and neurodevelopment after congenital CMV infection. Increasing evidence suggests early control of perinatal HIV infection has implications for neurocognitive functioning into school age. Lastly, the antiviral pleconaril has been studied for nearly two decades for treating severe enteroviral infections, with newer data supporting a role for this drug in neonates. Identifying common mechanisms for pathogenesis of viral CNS disease during this critical period of brain development is an important research goal, highlighted by the recent emergence of Zika virus as a potential cause of fetal neurodevelopmental abnormalities.

Topics: Acyclovir; Antiviral Agents; Brain; Cognition; Cognition Disorders; Encephalitis, Herpes Simplex; Enterovirus Infections; Female; Ganciclovir; HIV Infections; Humans; Infant, Newborn; Nervous System Diseases; Oxadiazoles; Oxazoles; Pregnancy; Valganciclovir; Virus Diseases

Herpes simplex encephalitis (HSE) is a rare disease, although it is the most common form of sporadic encephalitis worldwide. Recently, studies have provided important new insight into the genetic and immunological basis of HSE. However, even in the presence of antiviral treatment, mortality and morbidity remain relatively high. Therefore, precise and early diagnosis together with basic and clinical studies to gain better insight into the pathogenesis of HSE is a prerequisite for the development of improved prophylaxis and treatment of this severe disease.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Humans; Interferon-alpha; Interferon-beta; Simplexvirus; Toll-Like Receptor 3

Herpes simplex encephalitis (HSE) after neurosurgical procedures is extremely uncommon, and the few published case reports mainly described herpes simplex virus type 1 (HSV-1) as being culpable. We present a rare case of HSV-2 encephalitis after craniotomy and describe its pathophysiology and optimal management.. A 70-year-old woman underwent an elective resection of a recurrent left sphenoid wing meningioma and clipping of a left middle cerebral artery aneurysm, the latter having been found incidentally. She returned to our department with clinical findings suggestive of meningitis 12 days after the operation. Her lack of response to empiric antibiotic treatment, taken together with the lymphocyte-predominant initial cerebrospinal fluid obtained by lumbar puncture and the electroencephalographic indications of encephalopathy, led to the suspicion of a diagnosis of HSE, which was later confirmed by a polymerase chain reaction test positive for HSV-2. The patient was then successfully treated with intravenous acyclovir for 2 weeks followed by another week of oral acyclovir treatment before being discharged.. The present case stresses the importance of recognizing the relatively rare entity of HSE after craniotomy. Timely correct diagnosis will expedite the initiation of appropriate treatment.

Topics: Acyclovir; Aged; Antiviral Agents; Craniotomy; Encephalitis, Herpes Simplex; Female; Herpesvirus 2, Human; Humans; Treatment Outcome

Herpes simplex encephalitis (HSE) is the most common single cause of viral encephalitis in infants and children. Treated or untreated, it can be associated with considerable morbidity and mortality, and its presentation is usually insidious and non-specific. Prompt and careful investigation is important in order to establish the diagnosis so that treatment can be optimised. We address some common questions arising when diagnosing and treating presumed HSE throughout childhood.

Topics: Acyclovir; Antiviral Agents; Child; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant; Infant, Newborn; Male

Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) are highly prevalent viruses capable of establishing lifelong infection. Genital herpes in women of childbearing age represents a major risk for mother-to-child transmission (MTCT) of HSV infection, with primary and first-episode genital HSV infections posing the highest risk. The advent of antiviral therapy with parenteral acyclovir has led to significant improvement in neonatal HSV disease mortality. Further studies are needed to improve the clinician's ability to identify infants at increased risk for HSV infection and prevent MTCT, and to develop novel antiviral agents with increased efficacy in infants with HSV infection.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Herpes Genitalis; Herpes Simplex; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Keratitis, Herpetic; Male; Pregnancy; Pregnancy Complications, Infectious

Necrosis retiniana aguda por virus herpes simple tipo 1 a los tres años de una encefalitis herpetica.

Topics: Acyclovir; Antiviral Agents; Aspirin; Cataract Extraction; Causality; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Methylprednisolone; Middle Aged; Recurrence; Retinal Detachment; Retinal Hemorrhage; Retinal Necrosis Syndrome, Acute; Time Factors; Valacyclovir; Valine; Vitrectomy

Herpes simplex virus (HSV) hepatitis is an uncommon cause of liver failure, but may have a dramatic outcome. We herein present a case report of a liver graft infection by HSV-1 associated with liver failure and encephalitis. A complete hospital chart review of the case and a literature search were undertaken. Literature review suggests that herpes simplex acute liver failure is rare and associated with a poor prognosis, even with early treatment. Novel diagnostic and preventive approaches need to be instituted.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Fatal Outcome; Hepatitis, Viral, Human; Herpes Simplex; Herpesvirus 1, Human; Humans; Liver Failure, Acute; Liver Transplantation; Male; Middle Aged; Transplants

Herpes simplex virus is a common virus that causes a variety of clinical presentations ranging from mild to life-threatening. Orolabial and genital herpes are common disorders that can often be managed in an outpatient setting; however, some patients do present to the emergency department with those conditions, and emergency clinicians should be aware of possible complications in the pediatric population. Neonatal herpes is a rare disorder, but prompt recognition and initiation of antiviral therapy is imperative, as the morbidity and mortality of the disease is high. Herpes encephalitis is an emergency that also requires a high index of suspicion to diagnose. Herpes simplex virus is also responsible for a variety of other clinical presentations, including herpes gladiatorum, herpetic whitlow, eczema herpeticum, and ocular herpes. This issue reviews the common clinical presentations of the herpes simplex virus, the life-threatening infections that require expedient identification and management, and recommended treatment regimens.

Topics: Acyclovir; Antiviral Agents; Child; Child, Preschool; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant; Infant, Newborn; Male; Pregnancy Complications, Infectious

Herpes encephalitis (HE) is among the most common forms of viral encephalitis. Earlier publications indicate the development of acyclovir-refractory choreoathetosis in patients with HE. These reports suggest the development of secondary autoimmunity in the pathogenesis of HE. Combined methylprednisolone and acyclovir treatment reduced the appearance of brain abnormalities relative to treatment with acyclovir alone in a mouse model of encephalitis. We describe a case of a 19-month-old previously healthy girl presenting with sudden onset seizures and loss of consciousness. Initial polymerase chain reaction (PCR) tests for the presence of herpes simplex virus (HSV) were negative as were the tests for the limbic encephalitis antibodies. Steroids were administered with acyclovir to treat suspected autoimmune encephalitis as a result of the patient history of varicella vaccination. HSV PCR testing was positive on the 5th day; however, steroid treatment was continued due to the positive response seen in the patient. Steroid therapy was reduced on the 25th day of treatment due to the development of upper respiratory tract infection and the patient developed orofacial dyskinesia and choreoathetoid movements on the 28th day. Antibodies against N-methyl-d-aspartate receptor were detected in the in the serum and cerebrospinal fluid (CSF) on the 28th day. This case is an example of the emergence of autoimmune symptoms in the pathogenesis of HE.

Topics: Acyclovir; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antiviral Agents; Disease Progression; Encephalitis, Herpes Simplex; Female; Humans; Infant; Steroids; Treatment Outcome

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.

Topics: Acyclovir; Animals; Antiviral Agents; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Encephalitis, Herpes Simplex; Genes, Viral; Herpesvirus 1, Human; Humans; Mice; Microbial Sensitivity Tests

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.

Topics: Acyclovir; Antiviral Agents; DNA, Viral; Encephalitis, Herpes Simplex; Humans; Practice Guidelines as Topic

Herpes simplex virus-1 (HSV-1) is the most common cause of lethal sporadic encephalitis. Despite improved therapy with intraveneous acyclovir, HSV-1 encephalitis is associated with persistent severe neurological deficits. We report three cases of adult patients with HSV-1 encephalitis (HSE), discuss the current accepted guidelines for treatment as published by the Infectious Disease Society of America (IDSA) and review the literature pertaining to HSE. Our case presentations are consistent with the literature review noting a broad spectrum of clinical outcomes with HSE. We include the first published case of successful early transition to oral antiviral therapy. In the other two cases, repeat cerebrospinal fluid (CSF) analysis showed persistent lymphocytic pleocytosis necessitating prolonged viral suppression. Long-term neurological sequelae were noted in these two patients. The IDSA recommendation of 2-3 weeks of intraveneous acyclovir at 10 mg/kg every 8 h, depending on the clinical course, is sufficient for most cases of HSE. We recommend individualization of duration of treatment based on follow-up CSF analysis with quantification of HSV-1.

Topics: Acyclovir; Antiviral Agents; Cerebrospinal Fluid; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Male; Middle Aged

Topics: Acyclovir; Antiviral Agents; Brain; Cross-Sectional Studies; Diagnosis, Differential; Encephalitis, Herpes Simplex; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed

Encephalitis and postinfectious encephalitis represent two important conditions for the neurologist, both in terms of their presentations as neurologic emergencies and their potential to cause death or serious neurologic impairment. This article reviews the major infectious and noninfectious causes of encephalitis and discusses postinfectious encephalitis as an indirect effect of systemic illness.. Encephalitis caused by herpes simplex virus type 1 and West Nile virus are of major importance. In addition, within the past few years we have gained improved understanding of the neurologic syndromes caused by varicella-zoster virus, the recognition of enterovirus 71 as a significant human pathogen, and the realization that encephalitis may also occur by autoimmune mechanisms requiring immunosuppressive therapy. We have also learned that postinfectious encephalitis may be recurrent rather than monophasic, and that children and adults initially diagnosed with postinfectious encephalitis may later develop classic multiple sclerosis.. Encephalitis and postinfectious encephalitis present as neurologic emergencies requiring prompt diagnosis and initiation of treatment. Important concerns are to identify infectious conditions requiring antibiotic or antiviral therapy and postinfectious or other autoimmune encephalitides requiring immunosuppression.

Topics: Acyclovir; Adolescent; Antiviral Agents; Brain Diseases; Encephalitis; Encephalitis, Herpes Simplex; Encephalitis, Varicella Zoster; Encephalitis, Viral; Enterovirus Infections; Fatal Outcome; Female; Hashimoto Disease; Humans; Leukoencephalitis, Acute Hemorrhagic; Magnetic Resonance Imaging; Male; Middle Aged; West Nile Fever; Young Adult

Herpes simplex virus (HSV) is the cause of herpes simplex encephalitis (HSE), a devastating human disease which occurs in 2-4 cases per million/year. HSE results either from a primary infection or virus reactivation, in accordance with the common pattern of HSV infection which is a chronic lifelong process. However its pathophysiology remains largely unknown and its poor prognosis is in contrast with the usually good tolerance of most clinical herpetic manifestations. HSE is due to HSV type 1 (HSV-1) in most cases but HSV type 2 (HSV-2) may be also implicated, especially in infants in the context of neonatal herpes. Polymerase chain reaction detection of HSV DNA in cerebrospinal fluid is the diagnosis of choice for HSE. Acyclovir, a nucleoside analogue which inhibits viral DNA polymerase activity, is the reference treatment of HSE while foscarnet constitutes an alternative therapy and the efficacy of cidofovir is currently uncertain in that context. The emergence of HSV resistance to acyclovir, a phenomenon which is mainly observed among immunocompromised patients, is a current concern although no case of HSE due to an acyclovir-resistant HSV strain has been reported to date. Nevertheless the identification and development of novel therapeutic strategies against HSV appears to be a non dispensable objective for future research in virology.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Humans; Simplexvirus; Virus Latency; Virus Replication

Topics: Acyclovir; Aged; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Temporal Lobe

The development of novel strategies to eradicate herpes simplex virus (HSV) is a global public health priority. While acyclovir and related nucleoside analogues provide successful modalities for treatment and suppression, HSV remains highly prevalent worldwide and is a major cofactor fueling the HIV epidemic. HSV is the predominant cause of genital ulcerative disease, and neonatal and sporadic infectious encephalitis. Asymptomatic shedding, which occurs more frequently than previously appreciated, contributes to viral transmission. Acyclovir resistance may be problematic for immunocompromised patients and highlights the need for new safe and effective agents. Ideally, vaccines to prevent infection, drugs to inhibit the establishment of or reactivation from latency, or vaginal microbicides to prevent sexual and perinatal transmission are needed to control the epidemic. This review summarizes current therapeutic options and strategies in development.

Topics: Acyclovir; Anti-Infective Agents; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Herpes Genitalis; Herpes Simplex; HIV Infections; Humans; Infant, Newborn; Keratitis, Herpetic; Male; Pregnancy; Stomatitis, Herpetic; Syndrome; Viral Vaccines

Current microbial diagnostics enable rapid and specific identification of the agents causing intrauterine and perinatal infections, and CT and MRI allow precise characterization of the central nervous system effects of these pathogens. Although infections with Toxoplasma gondii, Toxoplasma pallidum, Toxoplasma cruzi, and cytomegalovirus cannot currently be prevented by immunization, postnatal therapy of infected neonates can substantially improve outcome. Therapy with acyclovir should be initiated whenever perinatal herpes simplex virus encephalitis is suspected. Despite these strategies, intrauterine and perinatal infections remain major causes of permanent deafness, vision loss, cerebral palsy, and epilepsy among children throughout the world.

Topics: Acyclovir; Anti-Infective Agents; Antiviral Agents; Brain; Cytomegalovirus Infections; Diagnostic Imaging; Encephalitis, Herpes Simplex; Female; Fetus; Humans; Pregnancy; Pregnancy Complications, Infectious; Rubella; Toxoplasmosis, Congenital

Dramatic progress has been made recently in diagnosing and treating herpes simplex virus encephalitis (HSVE). Advances in imaging technology have greatly enhanced our ability to diagnose the illness noninvasively. Acyclovir is of proven efficacy and is generally well-tolerated. The major clinical management problem is that the pathologic process in the brain is usually well-advanced before the patient presents, and the symptoms, particularly in newborns or infants, are often initially nonspecific. This, plus a too frequent failure to recognize the nature and seriousness of the process, results in further delay in diagnosis and treatment. Physicians need to develop an increased awareness of the early signs and symptoms of the presentation of HSVE, and of the imperative for early treatment.

Topics: Acyclovir; Antiviral Agents; Brain; Diagnosis, Differential; Encephalitis, Herpes Simplex; Herpesviridae Infections; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 6, Human; Herpesvirus 7, Human; Herpesvirus 8, Human; Humans; Magnetic Resonance Imaging; Simplexvirus; Tomography, X-Ray Computed

A child suffered from herpes simplex virus encephalitis at the age of 6 months; a late relapse occurred 8.5 years after the initial episode, the longest latency period reported. Radiologic and autopsy findings suggest local reactivation of latent herpes simplex virus as the cause of relapse. All cases of late relapse of herpes simplex virus encephalitis in the last 15 years are reviewed, with emphasis on clinical characteristics and possible mechanisms.

Topics: Acyclovir; Antiviral Agents; Child; Encephalitis, Herpes Simplex; Fatal Outcome; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Male; Recurrence; Virus Activation; Virus Latency

Children with herpes simplex virus encephalitis have a relapse in approximately 25% of cases, which rarely may present as a movement disorder, most often choreoathetosis. The anatomic basis for herpes simplex virus encephalitis-associated movement disorders has been poorly understood, because neuroimaging, to date, has not been able to show the direct involvement of the areas of the brain that typically govern such movements. We present a patient with abnormal involuntary movements after herpes simplex virus encephalitis, with new lesions on MRI between the time of initial presentation and the development of choreoathetosis. To our knowledge, this is the first patient with a post-herpes simplex virus encephalitis movement disorder with neuroradiographic evidence of thalamic involvement correlating with the onset of abnormal involuntary movements. We describe this patient and review the literature on movement disorders and herpes simplex virus encephalitis. Current understanding of the pathophysiology of post-herpes simplex virus encephalitis movement disorders proposes 2 possible mechanisms that may be responsible: reinfection with the resumption of viral replication, or a postinfectious, immune-mediated process.

Topics: Acyclovir; Athetosis; Basal Ganglia; Basal Ganglia Diseases; Chorea; Encephalitis, Herpes Simplex; Female; Follow-Up Studies; Humans; Infant; Magnetic Resonance Imaging; Risk Assessment; Severity of Illness Index; Treatment Outcome

This is a case report of PCR proven herpes simplex (HSV-1) encephalitis in a 26 years old immunocompetent adult taking an unusual course of acute intracerebral haematoma after successful and complete recovery with acyclovir therapy. This transient late complication was associated with a negative repeat CSF PCR for HSV suggesting that the initial 14 days course of acyclovir was successful in the eradication of the herpes virus infection as recommended by the International Herpes Management Forum (IHMF). The location of the haematoma corresponded to the initial encephalitic area involving the medial temporal lobe structures. Despite this late neuroradiologic complication, after day 18 of symptom onset, the patient had a favourable neurological outcome. To the best of our knowledge, this is the second report of the unusual, rare, and late neuroimaging complication of acute intracerebral haematoma formation after complete recovery from treated HSVE with favourable clinical outcome. The literature is reviewed and plausible aetiology is discussed.

Topics: Acyclovir; Adult; Antiviral Agents; Cerebral Hemorrhage; Encephalitis, Herpes Simplex; Hematoma; Humans; Male; Temporal Lobe

Herpes simplex virus (HSV) encephalitis is a rare association with pediatric neurosurgical pathologies.. A 13-year-old boy was diagnosed with an inoperable, biopsy-proven pontine grade II astrocytoma. During radiotherapy, he developed status epilepticus controlled by thiopentone with intubation and ventilation. Empiric cefotaxime and aciclovir were given. Lumbar cerebrospinal fluid (CSF) showed a normal white cell count, normal glucose, and a slightly elevated protein level. However, the CSF showed a positive polymerase chain reaction (PCR) for HSV type 1 DNA. Intravenous aciclovir was given for 21 days and foscarnet for 7 days. He was extubated after 4 weeks at which time he was aphasic with spastic diplegia. After 8 weeks, MRI brain scan showed the typical bitemporal pattern of HSV encephalitis. He made slow improvement but died 8 months after diagnosis from tumor progression.. HSV encephalitis is a rare but life threatening complication in neurosurgical patients. A low threshold for both investigation with CSF PCR and empirical treatment with intravenous aciclovir is warranted. As in this case, initial microscopic examination of the CSF may be normal. The literature on HSV encephalitis in neurosurgical patients is discussed.

Topics: Acyclovir; Adolescent; Antiviral Agents; Astrocytoma; Brain Stem Neoplasms; Encephalitis, Herpes Simplex; Fatal Outcome; Herpesvirus 1, Human; Humans; Male; Radiotherapy

Topics: Acyclovir; Adrenal Cortex Hormones; Antiviral Agents; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Polymerase Chain Reaction; Serologic Tests

Topics: Acyclovir; Adrenal Cortex Hormones; Antiviral Agents; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Humans; Practice Guidelines as Topic; Simplexvirus; Vidarabine; Virus Latency; Virus Replication

Topics: Acyclovir; Encephalitis, Herpes Simplex; Humans

A 24-year-old man was admitted to our hospital because of consciousness disturbance, a stiff neck and various brainstem symptoms including a right one-and-a-half syndrome and right peripheral facial palsy a week after an episode of pharyngitis and right facial herpes simplex. Magnetic resonance imaging of the brain on admission showed high-signal intensities in the right pontine tegmentum, right cerebellar peduncle and vermis on fluid-attenuated inversion recovery imaging. Examination of cerebrospinal fluid yielded mononuclear pleocytosis, elevated protein and increased IgM antibodies to herpes simplex virus (HSV) by enzyme immunoassay. HSV-1 specific antibodies also were detected in serum by neutralization test. We gave a diagnosis of brainstem encephalitis caused by HSV-1. The patient was successfully treated with high dose of acyclovir, steroid and intravenous immunoglobulin. He was discharged without any neurologic sequelae. We herein presented a case of atypical encephalitis due to HSV-1 involving mainly the brainstem with possible infection via right trigeminal nerve and summarized recent 35 cases with herpetic brainstem encephalitis since 1990.

Topics: Acyclovir; Adult; Antiviral Agents; Bell Palsy; Brain Stem; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Male; Trigeminal Nerve Diseases

Many cases of acute retinal necrosis caused by HSV-2 have been reported in children, teenagers, and young adults as a result of reactivation of congenital or neonatal infections, which may have been subclinical. Pediatricians should be aware of this entity and alert to recurrences that may be delayed by years.

Topics: Acyclovir; Antiviral Agents; Child; Encephalitis, Herpes Simplex; Female; Herpesvirus 2, Human; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Retinal Necrosis Syndrome, Acute; Valacyclovir; Valine; Virus Activation

Topics: Acyclovir; Antiviral Agents; Cat-Scratch Disease; Child; Encephalitis; Encephalitis, Herpes Simplex; Encephalomyelitis, Acute Disseminated; Enterovirus Infections; Epstein-Barr Virus Infections; Humans; Influenza, Human; Pneumonia, Mycoplasma; Prognosis; Rabies; West Nile Fever

Topics: Acyclovir; Antiviral Agents; Central Nervous System Diseases; Encephalitis; Encephalitis, Herpes Simplex; Enterovirus; Humans; Mycoplasma pneumoniae

Herpes simplex virus type 1 encephalitis (HSE) is the most frequent cause of severe sporadic viral encephalitis. In spite of the advanced modern methods for the treatment of HSE it is still associated with high mortality. Early diagnosis and prompt antiviral therapy with acyclovir are essential to improve prognosis and to prevent severe neurologic sequels.. This review summarizes the current knowledge on the pathogenesis, diagnosis, clinical presentation, and treatment of herpes simplex virus type 1 encephalitis. Characteristic features including magnetic resonance imaging (MRI) are illustrated by a typical case.

Topics: Acyclovir; Adult; Antiviral Agents; Electroencephalography; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Male; Prognosis; Time Factors

Herpes simplex encephalitis (HSE) is a life-threatening consequence of herpes simplex virus (HSV) infection of the central nervous system (CNS). Although HSE is rare, mortality rates reach 70% in the absence of therapy and only a minority of individuals return to normal function. Antiviral therapy is most effective when started early, necessitating prompt diagnosis. The International Herpes Management Forum (IHMF) has issued guidelines to aid the diagnosis and treatment of HSE. Polymerase chain reaction (PCR) of the cerebrospinal fluid (CSF) is the diagnostic method of choice for HSE, but negative results need to be interpreted in the context of the patient's clinical presentation and the timing of the CSF sampling. CSF virus culture is of little value in all but patients under the age of 6 months. CSF (intrathecal) antibody measurements are not recommended for acute diagnostic purposes. However, demonstration of an intrathecal HSV antibody response may be helpful in retrospective diagnosis or in cases in which CSF is sampled only late after onset of infection and PCR is negative. Serum HSV antibody measurements are not of utility in the diagnosis of HSV encephalitis in adults. In children and young adults, HSV serology may help define whether HSE is part of a primary or a reactivated HSV infection, although the clinical features, therapy, and prognosis of these two forms of HSV encephalitis are similar. The IHMF recommends that all patients with HSE receive intravenous aciclovir 10 mg/kg every 8 h for 14-21 days. Owing to the life-threatening nature of the disease, if there is a delay in diagnostic test results therapy should not be withheld until they become available. After completion of therapy, PCR of the CSF can confirm the elimination of replicating virus, aiding further management of the patient. Clinical trials of other antiviral agents (i.e. adjunctive oral valaciclovir after intravenous aciclovir) for the treatment of HSE are underway. Herpes infection of the CNS, especially with HSV-2, can also cause both monophasic and recurrent aseptic meningitis, as well as myelitis or radiculitis. Limited evidence suggests that aciclovir may be effective in its treatment. Recurrent aseptic meningitis is predominantly caused by HSV-2 infection, and is characterized by self-limited episodes of fever, meningismus and severe headache. Many cases are indistinguishable from cases previously classified as "Mollaret's meningitis", a term that should now be reserve

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Infusions, Intravenous; Meningitis, Viral; Practice Guidelines as Topic; Simplexvirus

The consequences of neonatal herpes simplex virus (HSV) infection can be severe. Disease can be localized to skin, eye and mouth (SEM disease), involve the central nervous system (CNS) or manifest as disseminated infection involving multiple organs. Most surviving infants in the latter two categories have neurological sequelae, and the mortality rate in the absence of therapy is very high (80%) for babies in the latter category. The International Herpes Management Forum (IHMF) has produced guidelines on the diagnosis, prevention and effective management of neonatal herpes. Neonatal herpes may occur in the absence of skin lesions, so if the infection is suspected, swabs of the oropharynx, conjunctiva, rectum, skin lesions, mucosal lesions and urine should be promptly taken and submitted for virus culture. Cerebrospinal fluid (CSF) should be submitted for polymerase chain reaction (PCR) detection of HSV DNA. Evidence for disseminated or CNS infection should be sought using liver function tests, complete blood cell count, CSF analysis and chest X-ray, if respiratory abnormalities are present. Neonates with suspected HSV infection should be treated with intravenous aciclovir (20 mg/kg) every 8 h for 21 days. If disease is localized to the SEM, treatment should be limited to 14 days. The neutrophil count for children receiving intravenous aciclovir should be monitored. If the absolute neutrophil count falls below 500/mm3, decreasing the aciclovir dose or administering granulocyte colony stimulating factor (GCSF) should be considered. At the end of therapy in CNS and disseminated disease, PCR assessment of CSF should be used and treatment continued if the child remains PCR positive at this site.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Granulocyte Colony-Stimulating Factor; Herpes Simplex; Humans; Infant, Newborn; Infusions, Intravenous; Meningitis, Viral; Polymerase Chain Reaction; Practice Guidelines as Topic; Simplexvirus

Relapse of herpes simplex virus (HSV) encephalitis following acyclovir therapy has been reported infrequently in children beyond the neonatal period. The pathogenic mechanism of the recurrence is not fully understood. We report two new cases that support a mechanism of latent HSV infection with reactivation of the disease. Our patients were 2 years (#1) and 8 months (#2) old at initial infection. Both presented with fever, lethargy, focal seizures, and focal motor abnormalities. Serum HSV antibodies (Abs) were negative. The patients were treated with acyclovir for 14 and 21 days, respectively. They were readmitted at 1 month, and 4 days after discharge, respectively, with recurrent lethargy, seizures, and choreo-athetoid movements. Serum and CSF HSV Abs were significantly increased. CSF PCR was positive. In patient # 2 acyclovir-sensitive HSV was isolated from a brain biopsy. Both patients were re-treated with acyclovir, but progressed to a neurovegetative state. In our cases, latent HSV infection and reactivation is the most likely explanation for recurrent encephalitis. The immuno-pathogenic mechanisms of the infection recurrence are discussed. Based on the reported cases in the literature, patients younger than 2 years of age and with lower total dose of acyclovir treatments have a higher risk of recurrence.

Topics: Acyclovir; Antiviral Agents; Child, Preschool; Encephalitis, Herpes Simplex; Humans; Infant; Male; Recurrence; Simplexvirus; Virus Activation

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.

Topics: Acyclovir; Adult; Animals; Child; Encephalitis, Herpes Simplex; Humans; Magnetic Resonance Imaging; Polymerase Chain Reaction; Radiography

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; Diagnostic Imaging; DNA, Viral; Encephalitis, Herpes Simplex; Humans; Immunoglobulins; Polymerase Chain Reaction; Simplexvirus

Within the past decade the management of acute HSV I encephalitis has been improved dramatically by the advent of the polymerase chain reaction (PCR), a method which has become the gold standard of diagnosis of HSV I encephalitis, replacing diagnostic uncertainties and, avoiding, in particular, invasive brain biopsy. Early detection of HSV II in the neonate is mandatory; however, prevention by Caesarean section and/or prenatal therapy of the mother are for this the best option. Very recently the causative agent of Mollaret's meningitis has proved to be, at least in part, HSV I or II. So far prospective randomized therapeutic trials are awaited for the treatment of Mollaret's meningitis using intravenous acyclovir or the more modern oral forms of virostatics (famciclovir, valaciclovir). For decades the causative agent of facial palsy (Bell's palsy) has been sought; only with the advent of PCR has this question been answered. Although one single study indicates the superiority of a combination of acyclovir plus prednisone, this finding has to be confirmed by a large scale prospective randomised double blind study. Nevertheless, if other causes for the clinical/neurological syndrome of peripheral facial palsy have been excluded, a combination therapy with acyclovir plus prednisone seems to be indicated in a patient with Bell's palsy.

Topics: Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Clinical Trials as Topic; Diagnosis, Differential; DNA, Viral; Encephalitis, Herpes Simplex; Facial Paralysis; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Polymerase Chain Reaction; Prednisone; Prognosis

Herpes simplex virus encephalitis (HSE) is the most frequent viral encephalitis, as a rule with the starting point and centre within the temporal lobe. If untreated, HSE is usually fatal, thus diagnosis has to be established rapidly. Treatment with Acyclovir should begin as soon as possible. As MRI is extremely sensitive in detecting the early inflammatory changes, it should be initially performed, especially as in the early stadium CT may be unspecific. We recommend the following examination protocol: coronar T1-weighted MR imaging before and after administration of gadopentetate dimeglumine, coronar FLAIR sequence and axial T2-weighted imaging. The diagnostic proof is to show the evidence of viral DNA by polymerase chain reaction (PCR) in cerebrospinal liquor.

Topics: Acyclovir; Encephalitis, Herpes Simplex; Humans; Image Enhancement; Magnetic Resonance Imaging; Sensitivity and Specificity; Temporal Lobe; Tomography, X-Ray Computed

Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; Dexamethasone; Diagnosis, Differential; Encephalitis, Herpes Simplex; Glucocorticoids; Herpesvirus 1, Human; Humans; Injections, Intravenous; Male; Middle Aged; Retinal Necrosis Syndrome, Acute; Virus Activation

Longitudinally designed case studies, reporting cognitive and psychosocial outcome of herpes simplex virus encephalitis (HSVE), were conducted prior to current antiviral medication usage and primarily in persons with either left hemispheric or bilateral temporal lobe involvement. The current study demonstrated relatively better outcome (cognitive recovery and functional independence for activities of daily life) in an individual treated with IV Acyclovir within hours of initial symptoms and whose CT scans showed right hemispheric involvement. In contrast with earlier case reports, no semantic specific categories of memory impairment were noted on serial assessment. The time from first symptoms to antiviral medical treatment appears to be the best predictor of outcome from HSVE. Historical case studies with relatively poorer outcome and differing deficits suggest survivors of HSVE are a heterogenous group. Variability in anatomic lesions and time to treatment contribute to outcome.

Topics: Activities of Daily Living; Acute Disease; Acyclovir; Aged; Antiviral Agents; Cognition; Emergency Treatment; Encephalitis, Herpes Simplex; Female; Humans; Time Factors; Treatment Outcome

To 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.. The 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.. Temporal 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.. This 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.

Topics: Acyclovir; Adrenal Cortex Hormones; Adult; Brain Edema; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Simplexvirus; Temporal Lobe; Treatment Outcome

Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority.. Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint.. The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group.. Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors.. NCT00031486.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Cognition Disorders; Encephalitis, Herpes Simplex; Female; Follow-Up Studies; Humans; Male; Middle Aged; Quality of Life; Valacyclovir; Valine; Young Adult

The recommended treatment for herpes simplex encephalitis (HSE) remains intravenous acyclovir. In resource-poor countries, however, intravenous formulations are usually unavailable or unaffordable. We report the penetration of acyclovir into the cerebrospinal fluid (CSF) in patients with HSE, treated with the oral prodrug valacyclovir at 1,000 mg three times daily. The oral therapy achieved adequate acyclovir concentrations in the CSF and may be an acceptable early treatment for suspected HSE in resource-limited settings.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Male; Valacyclovir; Valine

The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question.. GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage.. 372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients.. Current Controlled TrialsISRCTN45122933.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Antiviral Agents; Chemotherapy, Adjuvant; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Glucocorticoids; Humans; Middle Aged; Patient Selection; Research Design; Treatment Outcome; Young Adult

To describe the clinical and laboratory findings in cases of neonatal herpes simplex virus (HSV) encephalitis.. Neonatal HSV encephalitis is a devastating infection which requires a high degree of clinical suspicion and rapid initiation of antiviral therapy.. We performed a retrospective search for all cases of HSV encephalitis within the two Saskatchewan pediatric tertiary care centers for the period of 1985-2001. Only those patients with consistent clinical presentations along with direct evidence of presence of HSV, such as positive cerebrospinal fluid (CSF) viral cultures, positive polymerase chain reaction (PCR) for HSV from CSF, or positive immunoglobulin G against HSV from neonatal blood, were selected.. Five male and four female infant patients were identified. At a mean age of presentation of 24 +/- 20 days, seizures occurred in six neonates, lethargy in six neonates, temperature changes in five neonates, and apnea in three neonates. Examination of CSF demonstrated an initial monocytosis or lymphocytosis, elevated CSF protein and depressed CSF glucose in 100% of patients. Electroencephalography (EEG) was abnormal in 100% of patients. Initial computerized tomography was abnormal in 55% of patients. Clinical follow-up over an average of two years demonstrated developmental delay in four patients and upper motor neuron findings in four patients. No patients suffered from postencephalitic epilepsy or mortality.. Neonatal HSV encephalitis most commonly presents with seizures, lethargy, and dysthermia. Cerebrospinal fluid testing and EEG have 100% sensitivity in cases with laboratory confirmation of HSV presence. Improvements in morbidity and mortality as compared to previous reports may relate to better recognition of this illness and acyclovir therapy. The lack of postinfection epilepsy in our series may also relate to better recognition and acyclovir therapy within this series of patients.

Topics: Acyclovir; Antiviral Agents; Brain; Electroencephalography; Encephalitis, Herpes Simplex; Female; Follow-Up Studies; Hematologic Tests; Humans; Infant, Newborn; Infant, Premature; Magnetic Resonance Imaging; Male; Saskatchewan; Tomography, X-Ray Computed

Topics: Acyclovir; Encephalitis, Herpes Simplex; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; Retinal Necrosis Syndrome, Acute

Herpes simplex encephalitis is the most common cause of sporadic viral encephalitis worldwide but presents as a diagnostic challenge at many settings due to its non-specific symptoms, which can be easily mistaken for systemic infection or metabolic encephalopathy. It has diverse range of presentations from fever, altered sensorium, nausea, vomiting, meningismus to seizures, neurological deficits and coma in advanced stages. It is associated with significant morbidity and mortality if treatment is delayed or inadequate. We here discuss a case of Herpes simplex virus (HSV) encephalitis which rapidly progressed to result in irreversible neurological insult due to delayed diagnosis and treatment.

Topics: Acyclovir; Administration, Intravenous; Antiviral Agents; Encephalitis, Herpes Simplex; Humans; Seizures

To identify the prevalence of herpes simplex encephalitis (HSE), factors influencing the duration of empirical acyclovir and frequency of acute kidney injury (AKI) in children with acute encephalitis syndrome (AES).. Prospective observational study.. Pediatric Emergency Department and PICU of a tertiary hospital in Northern India.. All consecutive, eligible children between 1 month and 12 years old presenting with AES, defined as altered consciousness for greater than 24 hours (including lethargy, irritability, or a change in personality) and two or more of the following signs: 1) fever (temperature ≥ 38°C) during the current illness, 2) seizures or focal neurological signs, 3) cerebrospinal fluid (CSF) pleocytosis, 4) electroencephalogram, and/or 5) neuroimaging suggesting encephalitis, who received at least one dose of acyclovir.. None.. Of the 101 children screened, 83 were enrolled. The median (interquartile range [IQR]) age was 3 years (1-6 yr). Thirty-one children (37.3%) were diagnosed with AES, of which four were labeled as probable HSE (three based on MRI brain, one based on serology). Scrub typhus, dengue, Japanese encephalitis, and mumps were the other infective causes. The median (IQR) duration of acyclovir therapy was 72 hours (24-264 hr); 21 children (25.3%) received acyclovir for less than 24 hours and 11 (13.3%) for greater than or equal to 14 days. New-onset AKI was seen in 18 children (21.7%) but was mostly transient. Death ( n = 8, 9.6%) and discontinuation of care due to futility or other reasons ( n = 15, 18%) were noted in 23 children (28%). Factors associated with duration of acyclovir greater than 7 days, on univariable analysis, were lower modified Glasgow Coma Score at admission, requirement of invasive ventilation, invasive intracranial pressure monitoring, and CSF pleocytosis (5-500 cells). On multivariable analysis, only CSF pleocytosis of 5-500 cells was associated with duration of acyclovir greater than 7 days.. Given the low prevalence of HSE, and the risk of AKI, this study sensitizes the need to review our practice on initiation and stopping of empirical acyclovir in children with acute encephalitis.

Topics: Acyclovir; Antiviral Agents; Child; Child, Preschool; Encephalitis, Herpes Simplex; Humans; Leukocytosis; Seizures

We reported on a case involving an older patient with HSV-1 encephalitis who simultaneously experienced the onset of peripheral nerve symptoms associated with the presence of anti-GM3 immunoglobulin G (IgG).. A 77-year-old male was admitted to hospital with high fever, weakness of both lower limbs, and an unstable gait. A CSF test revealed a strikingly increased protein level (1,002 mg/L, normative values: 150-450 mg/L) and MRI revealed hyper-signal lesions in the right temporal lobe, right hippocampus, right insula, and right cingulate gyrus. The CSF was positive for HSV PCR (HSV-1,17870). In addition, the serum samples were positive for CASPR2 antibodies (antibody titer: 1/10) and anti-GM3 immunoglobulin G (IgG) (+). The patient was diagnosed with HSV-1-induced peripheral nerve symptoms that were associated with encephalitis and the presence of anti-GM3 IgG and anti-CASPR2 antibodies. The patient had received included intravenous immunoglobulin, intravenous acyclovir, and corticosteroids therapy. At the one-year follow-up examination, he had regained the necessary skills associated with daily life.. Herpes simplex virus infection often induces encephalitis, and reaction to the virus may trigger an autoimmune response. Early diagnosis and treatment can avoid the progression of the disease to include autoimmune encephalitis.

Topics: Acyclovir; Aged; Encephalitis, Herpes Simplex; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunoglobulin G; Male; Peripheral Nervous System Diseases

Recurrent herpes simplex encephalitis (HSE) can easily induce autoimmune encephalitis (AE). However, there are few reports of anti-contactin-associated protein-2 (CASPR2)-related encephalitis, especially with positive anti-aquaporin 4 (AQP4) antibodies.. A 14-year-old boy was admitted to the Department of Neurology of the First Affiliated Hospital of Kunming Medical University for "headache, dizziness, and fever for four days" with positive anti-CASPR2 and anti-AQP4 antibodies in the cerebrospinal fluid.. Cranial MRI showed lesions in the right hippocampus, amygdala, and insular lobe, with local sulcus enhancement in the right insular, temporal, and frontal lobes. The fluid-attenuated inversion recovery was significantly enhanced. Human herpes virus type I was detected by cerebrospinal fluid metagenomic testing. The patient was diagnosed with AE secondary to HSE, with positive anti-CASPR2 and anti-AQP4 antibodies.. After 2 weeks of immunoglobulin and methylprednisolone immunomodulatory therapy, acyclovir antivirus, mannitol dehydration, reducing intracranial pressure, and other symptomatic support therapy.. The patient's symptoms significantly improved, with no complaints of discomfort, and he was discharged for observation. The patient was followed up a month after discharge and had no complaints of discomfort.. CASPR2 and anti-aquaporin-4 antibody-positive AE have not been reported to be positive. This case will raise awareness of CASPR2 and anti-aquaporin-4 antibody-positive AE secondary to HSE, strengthen diagnostic capacities, and provide advice to treat it.

Topics: Acyclovir; Adolescent; Autoimmune Diseases of the Nervous System; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Male

Encephalitis is a devastating neurologic disease often complicated by prolonged neurologic deficits. Best practices for the management of adult patients include universal testing for a core group of etiologies, including herpes simplex virus (HSV)-1, varicella zoster virus (VZV), enteroviruses, West Nile virus, and anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody encephalitis. Empiric acyclovir therapy should be started at presentation and in selected cases continued until a second HSV-1 polymerase chain reaction test is negative. Acyclovir dose can be increased for VZV encephalitis. Supportive care is necessary for other viral etiologies. Patients in whom no cause for encephalitis is identified represent a particular challenge. Management includes repeat brain magnetic resonance imaging, imaging for occult malignancy, and empiric immunomodulatory treatment for autoimmune conditions. Next-generation sequencing (NGS) or brain biopsy should be considered. The rapid pace of discovery regarding autoimmune encephalitis and the development of advanced molecular tests such as NGS have improved diagnosis and outcomes. Research priorities include development of novel therapeutics.

Topics: Acyclovir; Adult; Brain; Encephalitis; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 3, Human; Humans; Nervous System Diseases

To describe the clinical characteristics of anti-NMDAR encephalitis secondary to acute necrotizing encephalopathy caused by herpes simplex virus encephalitis in infants, and aid in its early recognition, diagnosis and treatment.. A total of 4 infants were included; all presented with fever, seizures, and progressive disturbances of consciousness and were diagnosed with herpes simplex virus (HSV-1) encephalitis. Cerebrospinal fluid (CSF) protein levels progressively increased, and the head MRI showed necrotizing encephalopathy. There was no significant improvement or recurrence after treatment with acyclovir, dexamethasone, or immunoglobulins. CSF reexamination at 3 weeks to 3 months showed positive anti-NMDAR IgG antibodies and gradual improvement after high-dose methylprednisolone therapy.. Infants with ANE associated with HSV can develop secondary anti-NMDAR encephalitis, recognition of which is critical to ensure the appropriate institution of immunotherapy after active CNS infection has been ruled out.

Topics: Acyclovir; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Brain Diseases; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Infant

Refractory hypotension is a life-threatening condition that can result from various causes. We report a rare case of refractory hypotension following herpes simplex virus type 1 encephalitis that was successfully treated with hormone therapy.. The patient was a 66-year-old male who was admitted to the hospital because of fever, chills, convulsions, and impaired consciousness. He developed respiratory failure and was intubated. Cerebrospinal fluid metagenomic sequencing confirmed herpes simplex virus type 1 infection. He received piperacillin-tazobactam for anti-infection, acyclovir for antiviral therapy, and dexamethasone for anti-inflammatory therapy. He had repeated episodes of hypotension despite fluid resuscitation and vasopressor therapy.. The diagnosis of herpes simplex virus type 1 encephalitis complicated by refractory hypotension was based on the patient's epidemiological history, clinical manifestations, laboratory tests, and imaging studies. Cerebrospinal fluid examination was the most important diagnostic method, which could detect viral nucleic acids. Head magnetic resonance imaging showed a large recent lesion in the right temporal-parietal and insular lobes.. The treatment of refractory hypotension mainly included anti-infection, antiviral, anti-inflammatory, and hormone therapy. Hormone therapy used methylprednisolone shock treatment until tapering withdrawal. Other treatments included fluid resuscitation, vasopressors, anticonvulsants, etc.. The patient's blood pressure stabilized after receiving methylprednisolone shock treatment, and his mean arterial pressure increased from 73 mm Hg to 92 mm Hg within 24 hours. Three months later, the patient's blood pressure was normal without medication, and he had a good social and physical recovery.. This case illustrates the possible role of hormone therapy in restoring blood pressure in patients with refractory hypotension following viral encephalitis. It suggests that adrenal insufficiency or autonomic dysfunction may be involved in the pathophysiology of this condition. Further studies are needed to confirm the efficacy and safety of hormone therapy in this setting.

Topics: Acyclovir; Aged; Anti-Inflammatory Agents; Antiviral Agents; Encephalitis, Herpes Simplex; Encephalitis, Viral; Hormones; Humans; Hypotension; Male; Methylprednisolone

Topics: Acyclovir; Encephalitis, Herpes Simplex; Humans; Immune Checkpoint Inhibitors

Prognosis of herpetic encephalitis remains severe, with a high proportion of deaths and sequelae. Its treatment is based on acyclovir, but the precise and most effective modalities of this treatment are not established. The objective of this study was to determine them.. For this, we carried out a descriptive, retrospective, monocentric study, using the current coding database at Marseille University Hospitals. Cohort was intended to be exhaustive for the disease, from January 2000 to June 2019, including patients hospitalized in intensive care and conventional hospitalization sector. Patients (n = 76) included were at least 16 years of age and had a clinical presentation, cerebral Magnetic Resonance Imaging, and/or electroencephalogram abnormalities consistent with herpetic encephalitis confirmed by a positive HSV-PCR in the CSF. Clinical data and treatment, including the doses actually administered to the patient, were compared according to patient's outcome.. The mortality rate was 12%, whereas 49% had complete recovery and 39% sequelae impeding independence. Poor outcome was statistically associated with persistence of confusion, aphasia, and impaired consciousness lasting more than 5 days, superinfection, status epilepticus, and length of stay in intensive care unit. A statistical decision tree, constructed using the Classification And Regression Tree model, to prioritize treatment management, showed two main factors that influence the outcome: the patient's weight, and the average daily acyclovir dose actually administered.. These results suggest to modify acyclovir management in herpetic encephalitis, for low-weight patients (< 79 kg) with a minimum dosage of 2550 mg/day (850 mg/ 8 h), when possible.

Topics: Acyclovir; Antiviral Agents; Body Weight; Disease Progression; Encephalitis, Herpes Simplex; Humans; Retrospective Studies

Bortezomib is proteasome inhibitor used in multiple myeloma treatment. The reactivation of herpes simplex virus (HSV) and varicella-zoster virus (VZV) during bortezomib-based therapy is a well-known adverse event. Antiviral prophylaxis is mandatory. Nevertheless, reports of herpesviral encephalitis are scarce.. A 57-year-old multiple myeloma patient who during CyBorD protocol (Bortezomib, cyclophosphamide, and dexamethasone), after a transient suspension of antiviral prophylaxis presented progressive headaches unresponsive to conventional analgesics, asthenia, fever, episodic visual hallucinations, and vesicular lesions in the right supraorbital and frontal region. Herpetic encephalitis was diagnosed after detecting herpes zoster in cerebrospinal fluid.. The patient was treated with acyclovir 500mg every 6 hours for 21 days, and subsequent valacyclovir prophylaxis achieving an excellent clinical evolution. Anti-myeloma treatment was changed to lenalidomide and dexamethasone achieving a durable complete response. Herpesviral encephalitis is a rare but severe complication associated with the use of Bortezomib, especially when patients did not receive acyclovir prophylaxis. However, a rapid detection based on the clinical suspicion, and the prompt start of treatment, may lead to overcome this adverse event.

Topics: Acyclovir; Amyloidosis; Antineoplastic Agents; Antiviral Agents; Boronic Acids; Bortezomib; Dexamethasone; Encephalitis, Herpes Simplex; Herpesvirus 3, Human; Humans; Middle Aged; Multiple Myeloma; Pyrazines

To describe the prevalence, associated factors, and clinical impact of an initial negative herpes simplex virus (HSV) polymerase chain reaction (PCR) in critically ill patients with PCR-proven HSV encephalitis.. Retrospective multicenter study from 2007 to 2017.. Forty-seven French ICUs.. Critically ill patients admitted to the ICU with possible/probable acute encephalitis and a positive cerebrospinal fluid (CSF) PCR for HSV.. None.. We included 273 patients with a median Glasgow Coma Scale score of 9 (6-12) at ICU admission. CSF HSV PCR was negative in 11 cases (4%), exclusively in lumbar punctures (LPs) performed less than 4 days after symptoms onset. Patients with an initial negative PCR presented with more frequent focal neurologic signs (4/11 [36.4%] vs 35/256 [13.7%]; p = 0.04) and lower CSF leukocytosis (4 cells/mm3 [3-25 cells/mm3] vs 52 cells/mm3 [12-160 cells/mm3]; p < 0.01). An initial negative PCR was associated with an increased delay between LP and acyclovir treatment (3 d [2-7 ] vs 0 d [0-0 d]; p < 0.01) and was independently associated with a poor neurologic outcome at hospital discharge (modified Rankin Scale score ≥ 4) (adjusted odds ratio, 9.89; 95% CI, 1.18-82.78).. In severe herpes simplex encephalitis, initial negative CSF HSV PCR occurred in 4% of cases and was independently associated with worse neurologic outcome at hospital discharge. In these patients, a systematic multimodal diagnostic approach including early brain MRI and EEG will help clinicians avoid delayed acyclovir initiation or early inappropriate discontinuation.

Topics: Acyclovir; Cerebrospinal Fluid; Critical Illness; Encephalitis, Herpes Simplex; Humans; Polymerase Chain Reaction; Prevalence; Simplexvirus

Topics: Acyclovir; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Simplexvirus

Herpes simplex virus (HSV) is a sporadic viral encephalitis agent that causes high mortality and morbidity, accompanied by neurological dysfunction findings. Acyclovir is the only antiviral treatment option that should be initiated in all patients with suspected encephalitis as soon as possible. Acyclovir is rarely possible to cause allergic reactions. It may occur in a wide range from generalized cutaneous rash to Stevens-Johnson syndrome. A case of HSV-1 encephalitis who had no treatment option other than intravenous acyclovir and was successfully treated with intravenous desensitization was presented in this report. A 59-year-old male patient was admitted to the emergency department with complaints of high fever and altered consciousness. Diagnostic lumbar puncture was performed and intravenous acyclovir treatment was initiated empirically with the preliminary diagnosis of encephalitis. On the third day of the treatment, HSV type 1 polymerase chain reaction (PCR) was detected as positive. Acyclovir treatment was discontinued due to the development of a severe allergic reaction on the fifth day of acyclovir treatment. Allergic symptoms of the patient regressed with discontinuation of acyclovir treatment and application of concomitant methylprednisolone treatment. The intravenous acyclovir desensitization protocol was applied to the patient, and the patient was successfully treated. In this case, it has been shown that intravenous acyclovir desensitization can be applied in the treatment of life-threatening infections with no treatment options other than intravenous acyclovir. Our case is the first adult case in the literature to be treated with intravenous acyclovir desensitization.

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Humans; Hypersensitivity; Male; Middle Aged

Topics: Acyclovir; Dyskinesias; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Infant; Lethargy

The article gives the clinical case of herpes simplex encephalitis relapse with the resistant seizures in a child. What we describe is a clinical approach towards the differential diagnostic of the seizures in structural epilepsy, which are resistant to anticonvulsants, or late herpes simplex encephalitis relapse. Good clinical perspective may be the indication of the intratecal synthesis of the IgG-specific antibodies to the herpes simplex type 1 and 2. Conducting etiotropic treatment with the appointment of acyclovir and pathogenetic therapy with the use of Cytoflavin contributed to the rapid and stable remission of epileptic seizures and regression of neurological deficit.. В статье представлено клиническое описание рецидива герпетического энцефалита (ГЭ) у ребенка, осложненного резистентными судорогами. Представлена тактика дифференциальной диагностики судорожного синдрома как проявления структурной эпилепсии, резистентной к противоэпилептической терапии, и позднего рецидива ГЭ. Диагностически ценным может быть обнаружение интратекального синтеза специфических IgG к вирусу простого герпеса 1-го и 2-го типов, что в представленном случае позволило подтвердить реактивацию герпетической инфекции в центральной нервной системе и явилось основанием для повторного курса специфической терапии. Проведение этиотропного лечения с назначением ацикловира и патогенетической терапии с применением Цитофлавина способствовало быстрой и стойкой ремиссии эпилептических приступов и регрессу неврологического дефицита.

Topics: Acyclovir; Child; Encephalitis, Herpes Simplex; Epilepsy; Herpes Simplex; Humans; Immunoglobulin G; Recurrence; Seizures

This study aims to explore the protective effect of Forsythiae Fructus extract(FFE) against herpes simplex virus encephalitis(HSE) in mice. To be specific, life extension rate of mice, viral load in mouse brain, levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interferon-α(IFN-α), and nitric oxide(NO) content in mouse brain were determined. Mice were classified into normal group, model group, acyclovir(ACV) group, and high-dose, medium-dose, and low-dose(100, 50, 25 mg·kg~(-1), respectively) FFE groups. HSE was induced in mice in corresponding groups. Then, the life extension rate was compared among groups. Viral load in brain was detected by real-time fluorescent quantitative PCR, the changes of TNF-α, IL-1β, and IFN-α in brain by enzyme-linked immunosorbent assay(ELISA), NO content in brain with nitrate reduction method, and pathological changes by hematoxylin-eosin(HE) staining. The result showed that the life extension rate in the high-dose, medium-dose, and low-dose FFE groups was 27.93%, 19.94%, and 10.66%, respectively, and the difference between the high-dose group and the model group was statistically significant(P<0.05). FFE decreased the viral load in brains of HSE mice. The levels of TNF-α, IL-1β, and IFN-α in ACV group and high-dose and medium-dose FFE groups were lower than those in the model group(P<0.01,P<0.05), and NO content in the three FFE groups was lower than that in the model group(P<0.01). In conclusion, FFE can improve the survival rate of HSE mice, reduce the load of herpes simplex virus type Ⅰ(HSV-1) in the brains of HSE mice, decrease the levels of inflammatory factors and NO content, and alleviate inflammation and pathological damage, thereby protecting the central nervous system.

Topics: Acyclovir; Animals; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Mice; Mice, Inbred BALB C; Nitric Oxide; Plant Extracts; Tumor Necrosis Factor-alpha

Topics: Acyclovir; Adult; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Humans; Magnetic Resonance Imaging; Migraine Disorders; Paralysis; Stroke; Young Adult

Central nervous system infections are a medical emergency, due to their high fatality and sequelae. Timely treatment is essential, and should be initially indicated empirically by clinical guidance, without microbiological certainty. Hence the importance of cerebrospinal fluid (CSF) analysis as an etiological and therapeutic guide in the crucial initial hours of management. We report a 57-year-old woman consulting for fever and altered mental status. A brain CAT scan was normal. A lumbar puncture disclosed a CSF with predominance of neutrophils. Suspecting a bacterial meningitis, antimicrobial treatment was started but 48 hours after, the patient did not improve. A new lumbar puncture disclosed a CSF with predominance of lymphocytes. The lymphocyte shift prompted a PCR that was positive for herpes virus. The patient was treated with acyclovir with a good evolution.

Topics: Acyclovir; Anti-Infective Agents; Antiviral Agents; Encephalitis, Herpes Simplex; Humans; Lymphocytes

Encephalitis is commonly caused by viruses. But beyond viruses there are so many causes of encephalitis. Encephalitis is the inflammation of the brain parenchyma due to any reason. As there are so many causes of encephalitis presentations are also variable. So to diagnose encephalitis a set of clinical, laboratory, electroencephalographic and neuroimaging criteria is used. Any children attend medical facility with sudden onset altered mental status along with any of the following features like fever, seizure, focal neurological signs should be evaluated as encephalitis. Viruses are the common cause of encephalitis. Along with infectious etiologies a vast group of noninfectious like autoimmune causes encephalitis also established. When children presented with above mentioned features along with behavior problem and or movement disorder there is a high suspicion of autoimmune etiology. Any suspected case of encephalitis should initiated treatment with antiviral along with supportive treatment; then step wise evaluation should be done to reach an etiological diagnosis. If infectious etiology could not be established or no significant improvement is found with antiviral therapy; immunomodulating therapy should be considered along. In all cases CSF analysis including biochemistry, cytology, viral PCR along with MRI and EEG should do; further investigations depend upon initial reports and clinical and epidemiological background. Dose and duration of antiviral depends on patient's age and response to treatment and comorbidity. Acyclovir 500mg/m²/BSA per dose 3 times daily for 21 days are adequate for HSV encephalitis. Monitoring of renal function is the essential. Adjuvant treatment with steroid and or manitol for cerebral edema and antiseizure drugs for convulsion is used where necessary. Meticulous fluid and nutritional support as well good general care improve outcome. In spite of adequate treatment of encephalitis mortality and morbidity was found a significant number of cases; among the morbidity behavior problem, seizure focal deficit are common.

Topics: Acyclovir; Antiviral Agents; Child; Encephalitis; Encephalitis, Herpes Simplex; Hashimoto Disease; Humans; Steroids; Viruses

Herpes simplex virus (HSV) rarely causes organ-invasive infection. Diagnosis and treatment for such infections are often delayed, and mortality is high. We present the first reported case of disseminated HSV-1 infection in an adult causing liver failure, myocarditis, and encephalitis in a patient who recovered after receiving parenteral acyclovir treatment.. A 46-year-old female presented with fever, chills, and malaise after 2 weeks of oral corticosteroid treatment for uveitis. She was diagnosed with disseminated HSV-1 infection with multi-organ involvement causing hepatitis, encephalitis, and myocarditis. Diagnosis was made timely using serum polymerase chain reaction (PCR) for HSV DNA and the patient was given intravenous acyclovir treatment promptly, which led to her survival without significant morbidity.. Clinicians should have a low threshold for suspecting HSV infection and ordering HSV PCR to decrease morbidity and mortality when there is a high clinical suspicion of systemic HSV infection with multi-organ involvement. Serum PCR for HSV DNA is an excellent modality for an initial diagnostic approach. Further research is warranted to elucidate causality between a course of corticosteroid therapy and systemic HSV-1 infection without major immunosuppressive comorbidities or treatments.

Topics: Acyclovir; Adrenal Cortex Hormones; Adult; Antiviral Agents; Encephalitis; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Middle Aged; Myocarditis

An 84-year male was brought in the emergency after a road traffic accident leading to polytrauma with deteriorating consciousness. Prolonged unexplained unconsciousness led to cerebrospinal fluid examination. The polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) was found to be positive for HSV-1 DNA. The patient was started on intravenous acyclovir and the consciousness level of the patient improved gradually. In this case, encephalitis was not suspected initially, because of the multiple traumatic injuries that needed management. Moreover, no features suggestive of encephalitis were present at the time of presentation, except for the non-specific symptom of drowsiness at the time of the accident. The patient was also diabetic and had chronic kidney disease as predisposing factors. It was primarily encephalitis which led to impaired consciousness that resulted in the road traffic accident in a very unlikely situation, i.e., hit by an ambulance inside the hospital. The reasons to suspect herpes simplex virus encephalitis (HSE) in this case were unexplained worsening level of consciousness, CSF findings suggestive of viral encephalitis along with highly deranged alanine aminotransferase (ALT) levels. This case highlights the importance of keeping a high index of suspicion for viral encephalitis in patients with risk factors, even in such a scenario of polytrauma. Key Words: Herpes simplex virus, Polytrauma, Viral encephalitis, Polymerase chain reaction.

Topics: Acyclovir; DNA, Viral; Encephalitis, Herpes Simplex; Encephalitis, Viral; Humans; Male; Simplexvirus

Topics: Acyclovir; Brain Ischemia; Encephalitis, Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; Ischemic Stroke; Recurrence; Simplexvirus; Stroke

Herpes simplex virus encephalitis (HSE) is the most common sporadic fatal encephalitis. Although timely administered acyclovir treatment decreases mortality, neuropsychiatric sequelae is still common among survivors. Magnetic resonance imaging is frequently utilized for the diagnosis of HSE, which typically involves temporal lobe(s) and can be mixed with brain tumors involving the same area. Here, we report a case of HSE, who received acyclovir with a delay of 90 days because of presumptive tumor diagnosis and survived with minimal sequelae.

Topics: Acyclovir; Adult; Antiviral Agents; Delayed Diagnosis; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Temporal Lobe; Treatment Outcome

Topics: Acyclovir; Administration, Intravenous; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Autoantibodies; Cerebrospinal Fluid; Encephalitis, Herpes Simplex; Humans; Magnetic Resonance Imaging; Male; Methylprednisolone; Middle Aged; Neoplasm Recurrence, Local; Plasmapheresis; Polymerase Chain Reaction; Simplexvirus; Treatment Outcome

We present a 24-year-old man with a 2-year history of progressive right-sided monocular vision loss with no other symptoms. An MRI showed a meningioma compressing the right optic nerve and the cavernous sinus. The tumour was partially resected. Eight days after discharge the patient was admitted with fever, a severe stabbing headache, insomnia, nausea and vomiting. A FilmArray panel and a cerebral biopsy were performed which were positive for herpes simplex virus 1 (HSV-1). An MRI of the brain showed asymmetric bilateral lesions in the frontobasal region with predominance of the right side. Acyclovir was started and continued until completing 21 days. A month after discharge, he started experiencing insomnia, trichotillomania, limb tremor, persistence of abulia, apathy and emotional lability. An HSV-1 encephalitis relapse was suspected, acyclovir and foscarnet were started. Due to the poor response to antiviral therapy CSF was tested, which was positive for anti-NMDA receptor encephalitis. A treatment course of intravenous immunoglobulin was started with a favourable outcome.

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Foscarnet; Humans; Male; Neoplasm Recurrence, Local; Young Adult

In January 2008, a 59-year-old man with a history of diabetes mellitus was admitted to our hospital with herpes simplex virus (HSV) encephalitis of his right temporal lobe, which was diagnosed by PCR testing of his cerebrospinal fluid (CSF). He was treated with intravenous acyclovir for three weeks and made a full recovery. On discharge, his CSF was negative for HSV on PCR testing. Seven years later, in March 2015, the man was readmitted to our hospital with fever, disorientation, and nominal dysphasia. Diffusion-weighted MRI of his head revealed a high-intensity area in his left temporal lobe. Testing of his CSF revealed a moderately increased monocyte count and HSV on PCR testing, so he was diagnosed with recurrent HSV encephalitis. He was treated with intravenous acyclovir for three weeks. On discharge, his CSF was negative for HSV on PCR testing, but he had mild residual amnesia. There have been few reports of HSV encephalitis with viral reactivation recurring after a long remission period in adults. This case illustrates the need for prolonged follow up of individuals with HSV encephalitis in order to detect recurrences.

Topics: Acyclovir; Aged; Cerebrospinal Fluid; Encephalitis, Herpes Simplex; Humans; Male; Polymerase Chain Reaction; Recurrence; Simplexvirus; Time Factors; Treatment Outcome

Following implementation of the FilmArray meningitis and encephalitis panel, which enables rapid syndromic cerebrospinal fluid testing, HSV testing doubled in children >60 days with suspected central nervous system infection at Children's Hospital Colorado. Acyclovir initiation was unchanged, but duration decreased. Diagnostic and antimicrobial stewardship is needed for MEP optimization.

Topics: Acyclovir; Adolescent; Antimicrobial Stewardship; Antiviral Agents; Central Nervous System Infections; Child; Child, Preschool; Encephalitis, Herpes Simplex; Female; Hospitals, Pediatric; Humans; Infant; Male; Meningitis, Viral; Molecular Diagnostic Techniques; Multiplex Polymerase Chain Reaction; Retrospective Studies; Simplexvirus

Current guidelines for severe herpes simplex virus infection recommend 21 days of intravenous therapy. The thrice-daily administration of intravenous acyclovir makes it challenging to deliver as outpatient therapy. We describe 2 cases with confirmed or presumed neonatal herpes simplex virus encephalitis treated with acyclovir administered as a continuous-infusion at home and review the pharmacologic and clinical evidence for continuous infusions of acyclovir.

Topics: Acyclovir; Antiviral Agents; Brain; Encephalitis, Herpes Simplex; Feasibility Studies; Female; Humans; Infant, Newborn; Infusions, Intravenous; Magnetic Resonance Imaging; Male; Treatment Outcome

Herpes simplex viruses (HSV) are neurotropic and known to cause central nervous system (CNS) infections. We aimed to describe the clinical and imaging features of cerebrovascular complications in patients with HSV CNS infections.. We reviewed records of patients with HSV infections by querying acyclovir use in a clinical registry of parenteral anti-infective therapy at a tertiary medical center from January 2010 until September 2018. One patient who met the inclusion criteria is subsequently added. Diagnostic criteria for HSV CNS infection were intrathecal presence of viral DNA with clinical signs of CNS involvement.. Of 36 patients who met the criteria for HSV CNS infections, cerebrovascular complications occurred in 6 patients (17%). Two patients with HSV-1 encephalitis had cerebrovascular complications (1 ischemic stroke, 1 intraparenchymal hemorrhage). Four patients had HSV-2 infection without encephalitis had cerebrovascular complications (3 ischemic strokes, 1 cerebral vein thrombosis). All 3 patients with ischemic strokes without encephalitis had pattern of vasculitis on vessel imaging on MRI with segmental narrowing and vessel wall irregularities of large intracranial arteries with circumferential wall enhancement.. Cerebrovascular complications of HSV can occur with encephalitis or as isolated events with vasculitis.

Topics: Acyclovir; Central Nervous System; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Simplexvirus

An 89-year-old man was admitted because of persistent fever and impaired consciousness. On admission, his consciousness level was E3V3M4 according to the Glasgow Coma Scale. MRI of the brain showed high intensity lesions in the bilateral cingulate gyri. In the cerebrospinal fluid, both cell counts and glucose level were in the normal ranges. He had received antibiotics and intravenous isotonic saline. On the fifth day of hospitalization, blood examination revealed elevation of anti-herpes simplex virus (HSV) immunoglobulin M antibody, and herpes simplex encephalitis (HSE) was diagnosed. Despite treatment with acyclovir, his respiratory function and consciousness level deteriorated rapidly. On the eighth day, he died of respiratory failure. At autopsy, the brain showed multiple softenings of the gray and white matter in the hippocampus, amygdala, and temporal, insular, and cingulate cortices. Some of these lesions were hemorrhagic. Microscopic examination revealed that the lesions were necrotic and associated with perivascular inflammatory cell infiltration in the limbic system, hypothalamus, brainstem tegmentum area, and medulla. Eosinophilic intranuclear inclusions were rarely found in the astrocytes in the medulla. Immunohistochemistry revealed anti-HSV-1 antibody positive neurons in the brainstem tegmentum including reticular formation and the raphe nuclei. HSV-DNA was also detected in the postmortem cerebrospinal fluid. This was a rare case of HSE in which inflammation in the brainstem proved to be the cause of lethal respiratory failure.

Topics: Acute Disease; Acyclovir; Age of Onset; Aged, 80 and over; Antibodies, Viral; Autopsy; Biomarkers; Brain Stem; Diffusion Magnetic Resonance Imaging; Encephalitis, Herpes Simplex; Fatal Outcome; Humans; Immunoglobulin M; Male; Respiratory Insufficiency; Simplexvirus

Topics: Acyclovir; Aged; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed

We report a case of classic HSE with early neurological relapse 7 days after onset of acyclovir treatment secondary to cerebral venous thrombosis (CVT). The development of CVT after meningoencephalitis has been described with neurotropic viruses such as HSV, HIV, or enteroviruses and also bacterial or fungal agents. CVT is probably the consequence of the inflammation secondary to these infections. A diagnosis of CVT, although rarely described, should be systematically suspected in patients with HSE who present no or only moderate improvement, or early relapse of symptoms despite adapted acyclovir treatment.

Topics: Acyclovir; Anticoagulants; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Middle Aged; Sinus Thrombosis, Intracranial; Warfarin

A 71-year-old man presented with sudden onset, generalized tonic-clonic seizures and altered mental status. Initial brain magnetic resonance imaging was normal but a brain FDG-PET scan showed hypermetabolism in the left ventral striatum and septal area. Initial cerebrospinal fluid (CSF) examination showed mildly elevated protein but herpes simplex virus (HSV) polymerase chain reaction (PCR) was negative. A repeat CSF examination performed 9 days later showed a positive HSV PCR. Histopathological and immunohistochemical examination of autopsy specimen confirmed the presence of CD45+ lymphocytes and HSV antigen, suggesting the presence of both inflammation and viral infection corresponding to PET abnormality.

Topics: Acyclovir; Aged; Antiviral Agents; Encephalitis, Herpes Simplex; Fatal Outcome; Fluorodeoxyglucose F18; Humans; Male; Positron-Emission Tomography; Radiopharmaceuticals; Septum of Brain; Ventral Striatum

Herpes simplex virus (HSV) encephalitis affects 2-4 people per million/year. Immunocompomised patients can have atypical presentations of HSV encephalitis, including a lack of cerebrospinal fluid (CSF) pleocytosis. We present the case of a patient who was receiving ustekinumab therapy for psoriasis which inhibits interleukin (IL)-12 and IL-23 signalling pathways. The initial presentation was suggestive of encephalitis, but he was discharged prior to the reporting of HSV positivity due to the lack of CSF pleocytosis. On representation, he had worsening symptoms and imaging showed midline shift, indicating cerebral oedema despite the immunosupressant effects of ustekinumab. He required intensive care unit support and treatment with high dose aciclovir and dexamethasone; after a month of treatment he made a good recovery. This case is the first to report a link between ustekinumab and HSV encephalitis, and also emphasises that imunocompromised patients can lack CSF pleocytosis and develop significant cerebral oedema which responds to immune suppression.

Topics: Acyclovir; Adult; Anti-Inflammatory Agents; Antiviral Agents; Brain Edema; Dermatologic Agents; Dexamethasone; Diagnosis, Differential; Encephalitis, Herpes Simplex; Humans; Immunocompromised Host; Male; Psoriasis; Ustekinumab

Acute retinal necrosis (ARN), which is characterized by peripheral necrotizing retinitis, severe retinal arteritis, and progressive inflammatory reaction in the vitreous and anterior chambers, has been reported in cases with herpes simplex encephalitis (HSE). It is a relatively rare complication secondary to HSE. However, cases presented with viral encephalitis following ARN were seldom reported.. A 43-year-old immunocompetent male patient manifested the aforesaid reverse situation. He developed HSE following 3-day systemic steroid therapy for abrupt ocular pain and rapidly decreased visual acuity, which was later diagnosed as ARN. Polymerase chain reaction (PCR) analysis of vitreous specimen verified herpes simplex virus-1 (HSV-1) infection.. HSE associated with ARN.. The patient was treated with intravenous acyclovir (500 mg every 8 h) for 21 days. A pulse of intravenous methylprednisolone, 500 mg/d for 5 days was given as an anti-inflammatory therapy, followed by prednisone taper.. The patient's neurological symptoms got improved very soon after the therapy, but his vision acuity remained no perception of light in both eyes.. The present case indicates that ARN can also be a risk factor for HSE. Once ARN was suspected, corticosteroid should be applied with caution and in combination with antiviral treatment to avoid progressive duplication of virus and its spread to the brain.

Topics: Acyclovir; Adult; Anti-Inflammatory Agents; Antiviral Agents; DNA, Viral; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompromised Host; Male; Methylprednisolone; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute

To determine the association of the use of the multiplex assay meningitis/encephalitis panel with clinical management of suspected meningitis.. A cross-sectional study was conducted with children 0 to 18 years of age who received a lumbar puncture within 48 hours of admission for an infectious workup. Patient demographic and presenting information, laboratory studies, and medication administration were collected. The primary measure was length of stay (LOS) with secondary measures: time on antibiotics, time to narrowing antibiotics, and acyclovir doses. LOS and antibiotic times were stratified for outcomes occurring before 36 hours. Logistic regression analysis was used to account for potential confounding factors associated with both the primary and secondary outcomes. A value of. Meningitis panel use was associated with a higher likelihood of a patient LOS <36 hours (. Use of the meningitis panel was associated with a decreased LOS, time to narrowing of antibiotics, and fewer acyclovir doses. This likely is a result of the rapid turnaround time as compared with cerebrospinal fluid cultures. Additional studies to examine the outcomes related to this change in management are warranted.

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Cross-Sectional Studies; Encephalitis, Herpes Simplex; Enterovirus Infections; Female; Humans; Infant; Infant, Newborn; Length of Stay; Male; Meningitis, Bacterial; Meningitis, Pneumococcal; Meningitis, Viral; Real-Time Polymerase Chain Reaction; Retrospective Studies; Roseolovirus Infections; Spinal Puncture

The incidence of neonatal herpes simplex virus (nHSV) infections is monitored periodically in the Netherlands, yet management and outcome is unknown. Comprehensive national guidelines are lacking. We aim to describe management and outcome in the last decade to explore current diagnostic and therapeutic challenges. We aim to identify possible variability in management of patients with a suspected nHSV infection.. We conducted a retrospective case series of management and outcome of nHSV infections at 2 tertiary care center locations in the Netherlands.. An nHSV infection was diagnosed in 1% (12 of 1348) of patients in whom polymerase chain reaction for HSV was performed. Of the patients with nHSV infection, 3 of 12 died, and 4 of 9 (44%) survivors suffered neurologic sequelae. Neurologic symptoms at presentation were seen in only 2 of 8 patients with nHSV encephalitis. A cerebral spinal fluid analysis was performed in 3 of 6 patients presenting with skin lesions. Only 3 of 6 patients with neurologic symptoms received suppressive therapy. nHSV infection was diagnosed in 8 of 189 (4%) patients who were empirically treated.. Management of nHSV infection, particularly when presented with skin lesions, is inconsistent. Many infants without a HSV infection are exposed to antiviral medication. There is substantial interhospital variation in diagnostic and therapeutic management of a suspected infection. Comprehensive guidelines need to be developed to standardize management of suspected nHSV infection.

Topics: Acyclovir; Antiviral Agents; Disease Management; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Male; Netherlands; Polymerase Chain Reaction; Practice Patterns, Physicians'

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.. 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.. 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).. 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.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Antiviral Agents; Brain; Cohort Studies; Encephalitis, Herpes Simplex; Female; Germany; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Polymerase Chain Reaction; Retrospective Studies; Tomography, X-Ray Computed; Young Adult

Brain granuloma occurs under certain conditions. Herpes simplex virus (HSV) causes granulomatous encephalitis in children; however, it has been rarely reported in adults. A 74-year-old man with a history of herpes simplex encephalitis suffered recurrent seizures. Brain magnetic resonance imaging revealed a mass lesion and resection was performed. A polymerase chain reaction using a brain biopsy specimen was positive for HSV DNA; thus, the patient was diagnosed with HSV-associated granulomatous encephalitis. After administering acyclovir, the patient showed improvement. HSV can cause granulomatous encephalitis in adults, and acyclovir can be used for its treatment.

Topics: Acyclovir; Aged; Antiviral Agents; Brain Stem; Encephalitis, Herpes Simplex; Granuloma; Humans; Male; Simplexvirus; Treatment Outcome

Herpes simplex encephalitis (HSE) is the most common cause of sporadic focal encephalitis worldwide. Acyclovir is the treatment of choice of HSE since the 1980s. After the widespread use of acyclovir, HSE related mortality rate had reduced but resistant strains emerged. Acyclovir resistant HSV incidence was reported as about 0.5 % and 3.5 %-10 % in immunocompetent and immunocompromised patients, respectively. Herein, a 12-year-old immunocompetent patient with HSV-1 encephalitis who was successfully treated with combined acyclovir and foscarnet therapy is described. In the case of deteriorating clinical condition under acyclovir treatment even if the absence of demonstration of increased CSF HSV viral load, the possibility of acyclovir resistant HSE and the addition of foscarnet to the acyclovir treatment might be considered.. La encefalitis por herpes simple (EHS) es la causa más frecuente de encefalitis focal esporádica en todo el mundo. El aciclovir es el tratamiento preferido para la EHS desde la década de 1980. Después del uso generalizado del aciclovir, se redujo la tasa de mortalidad relacionada con la EHS pero surgieron cepas resistentes. Se ha informado que la incidencia de virus del herpes simple (VHS) resistente al aciclovir es del 0,5 % y del 3,5 %-10 % aproximadamente en los pacientes inmunocompetentes e inmunocomprometidos, respectivamente. En este artículo, describimos el caso de un paciente inmunocompetente de 12 años de edad con encefalitis por VHS-1 tratado satisfactoriamente con aciclovir y foscarnet. En el caso de una condición clínica que desmejora con el tratamiento con aciclovir, incluso si no se demuestra un aumento de la carga viral del VHS en el líquido cefalorraquídeo, se podría considerar la posibilidad de EHS resistente al aciclovir y el agregado de foscarnet al tratamiento con aciclovir.

Topics: Acyclovir; Antiviral Agents; Child; Drug Combinations; Drug Resistance, Viral; Encephalitis, Herpes Simplex; Foscarnet; Humans; Male; Remission Induction; Simplexvirus; Treatment Failure

Recently some authors have suggested that oral valaciclovir 1 g q8h is a valid alternative to intravenous aciclovir for herpes encephalitis. We are concerned about numerous caveats that we think have not been sufficiently addressed to allow such use outside of a controlled research setting.

Topics: Acyclovir; Drug Administration Routes; Encephalitis, Herpes Simplex; Humans; Tissue Distribution; Valacyclovir

To develop an endogenous rodent model of postinfectious anti-NMDA receptor (NMDAR) encephalitis.. Six mice were inoculated intranasally with herpes simplex virus (HSV) 1 and subsequently treated with acyclovir for 2 weeks. Serum was collected at 3, 6, and 8 weeks postinoculation and tested for NMDAR antibodies through a cell-based assay. Eight weeks postinoculation, mice were killed and their brains were sectioned and immunostained with antibodies to postsynaptic density (PSD)-95 and NMDARs. Colocalization of hippocampal PSD-95 and NMDAR clusters, representing postsynaptic membrane NMDARs, was quantified via confocal imaging. Hippocampi were additionally analyzed for NMDAR and PSD-95 protein using Western blot analysis.. Four of 6 mice (67%) developed serum antibodies to NMDARs: 1 at 3 weeks, 1 at 6 weeks, and 2 at 8 weeks postinoculation. As compared to inoculated mice that did not develop NMDAR antibodies, immunofluorescence staining revealed decreased hippocampal postsynaptic membrane NMDARs in mice with serum antibodies at 8 weeks postinoculation. Western blot analysis showed that mice that had NMDAR antibodies at 8 weeks had decreased total NMDAR but not PSD-95 protein in hippocampal extracts (. Mice inoculated intranasally with HSV-1 developed serum NMDAR antibodies. These antibodies were associated with reduced hippocampal NMDARs, as has been shown in previous models where antibodies from patients with anti-NMDAR encephalitis were infused into mice, paving the way for future studies into the pathophysiology of autoimmune encephalitides.

Topics: Acyclovir; Animals; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antibodies; Disease Models, Animal; Disks Large Homolog 4 Protein; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Hippocampus; Mice, Inbred BALB C; Receptors, N-Methyl-D-Aspartate

The gut commensal Bacteroides fragilis or its capsular polysaccharide A (PSA) can prevent various peripheral and CNS sterile inflammatory disorders. Fatal herpes simplex encephalitis (HSE) results from immune pathology caused by uncontrolled invasion of the brainstem by inflammatory monocytes and neutrophils. Here we assess the immunomodulatory potential of PSA in HSE by infecting PSA or PBS treated 129S6 mice with HSV1, followed by delayed Acyclovir (ACV) treatment as often occurs in the clinical setting. Only PSA-treated mice survived, with dramatically reduced brainstem inflammation and altered cytokine and chemokine profiles. Importantly, PSA binding by B cells is essential for induction of regulatory CD4

Topics: Acyclovir; Animals; Antiviral Agents; B-Lymphocytes; Bacteroides fragilis; Chlorocebus aethiops; Disease Models, Animal; Encephalitis, Herpes Simplex; Female; Gastrointestinal Microbiome; Herpesvirus 1, Human; Host Microbial Interactions; Humans; Interleukin-10; Male; Mice; Mice, Knockout; Polysaccharides, Bacterial; Symbiosis; T-Lymphocytes; Vero Cells

A 60-year-old man with a history of severe herpes simplex virus type 1 (HSV-1) encephalitis 2 years prior presented with acute onset of visual loss in the left eye. Dilated funduscopic examination showed retinitis and occlusive vasculitis with retinal necrosis. PCR of the vitreous fluid was positive for HSV-1, and he was diagnosed with acute retinal necrosis (ARN) due to HSV-1. The patient was treated with intravenous acyclovir and intravitreous foscarnet for 2 weeks, followed by high dose oral valacyclovir for 2 weeks. He was subsequently placed on planned life-long suppressive valacyclovir. His case demonstrates that acute visual loss concomitant with or subsequent to HSV-1 encephalitis warrants suspicion of ARN. Prompt therapy with effective antiviral medication is necessary to reduce the risk of sight-threatening complications. Chronic suppression with oral antiviral therapy after ARN is recommended to prevent involvement of the contralateral eye, though there is no consensus on the duration and dosage of antivirals.

Topics: Acute Disease; Acyclovir; Antiviral Agents; Diagnosis, Differential; Encephalitis, Herpes Simplex; Eye Infections, Viral; Foscarnet; Herpesvirus 1, Human; Humans; Intravitreal Injections; Male; Middle Aged; Ophthalmoscopes; Rare Diseases; Retinal Necrosis Syndrome, Acute; Treatment Outcome; Valacyclovir

A 75-year-old woman presented with new onset of confusion, intense episodic dizziness and formed visual hallucinations. Herpes simplex encephalitis and non-convulsive temporal lobe seizures were confirmed with cerebrospinal fluid (CSF) and electroencephalography testing. In addition, her hospital course was complicated by syndrome of inappropriate antidiuretic hormone secretion and atonic bladder contributing to an episode of urinary tract infection. After completing 3 weeks of acyclovir treatment, the patient became obtunded with right arm choreiform movements and persistent inflammatory CSF findings not attributable to persistent herpes simplex virus infection or other confounding factors. The patient responded to steroid treatment. Repeated autoimmune and paraneoplastic evaluations were negative. Both clinical (cognitive testing and atonic bladder) and CSF inflammatory finding improved in the follow-up period.

Topics: Acyclovir; Aged; Antiviral Agents; Chorea; Electroencephalography; Encephalitis; Encephalitis, Herpes Simplex; Female; Glucocorticoids; Humans; Inappropriate ADH Syndrome; Methylprednisolone; Seizures; Urinary Bladder, Underactive; Urinary Retention; Urinary Tract Infections

Topics: Acyclovir; Antiviral Agents; Aphasia; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Middle Aged; Polymerase Chain Reaction; Stroke

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.

Topics: Acyclovir; Antiviral Agents; Biomarkers; Central Nervous System Infections; DNA, Viral; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Retrospective Studies; Treatment Outcome

Pritelivir, a helicase-primase inhibitor, has excellent in vitro and in vivo activity against human herpes simplex virus (HSV). Mice lethally infected with HSV type 1 or 2, including acyclovir-resistant strains, were treated 72 h after infection for 7 days with pritelivir or acyclovir. Both drugs were administered orally twice daily either alone or in combination. Dosages of pritelivir from 0.3 to 30 mg/kg reduced mortality (P < 0.001) against HSV-1, E-377. With an acyclovir resistant HSV-1, 11360, pritelivir at 1 and 3 mg/kg increased survival (P < 0.005). With HSV-2, MS infected mice, all dosages higher than the 0.3 mg/kg dose of pritelivir were effective (P < 0.005). For acyclovir resistant HSV-2, strain 12247, pritelivir dosages of 1-3 mg/kg significantly improved survival (P < 0.0001). Combination therapies of pritelivir at 0.1 or 0.3 mg/kg/dose with acyclovir (10 mg/kg/dose) were protective (P < 0.0001) when compared to the vehicle treated group against HSV-2, strain MS (in line with previous data using HSV-1). An increased mean days to death (P < 0.05) was also observed and was indicative of a potential synergy. Pharmacokinetic studies were performed to determine pritelivir concentrations and a dose dependent relationship was found in both plasma and brain samples regardless of infection status or time of initiation of dosing. In summary, pritelivir was shown to be active when treatment was delayed to 72 h post viral inoculation and appeared to synergistically inhibit mortality in this model in combination with acyclovir. We conclude pritelivir has potent and resistance-breaking antiviral efficacy with potential for the treatment of potentially life-threatening HSV type 1 and 2 infections, including herpes simplex encephalitis.

Topics: Acyclovir; Animals; Antiviral Agents; Disease Models, Animal; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Humans; Mice; Pyridines; Sulfonamides; Thiazoles; Tissue Distribution; Treatment Outcome

Topics: Acyclovir; Aged; Antiviral Agents; Drug Resistance, Viral; Encephalitis, Herpes Simplex; Female; Humans; Immunocompromised Host; Thymidine Kinase

We present a case of cerebral venous sinus thrombosis (CVST) as a rare complication of herpes simplex virus (HSV) encephalitis. A young man with no pertinent medical history was diagnosed with HSV encephalitis. After initial treatment, he showed improvement in symptomatology until day 6 when he acutely developed new neurological deficits. An urgent MRI brain showed changes in left temporal lobe consistent with HSV encephalitis and lack of flow void in superior sagittal sinus. Subsequent magnetic resonance venography confirmed the diagnosis of superior sagittal sinus thrombosis along with thrombosis of bilateral frontoparietal cortical draining veins. Anticoagulation was immediately initiated and oral anticoagulation was continued for 1 year. He made complete recovery subsequently. Our case serves as a reminder for the treating clinicians to consider CVST in patients with HSV encephalitis who develop an unexpected new neurological deficits during early phase of appropriate treatment.

Topics: Acyclovir; Adult; Anticoagulants; Antiviral Agents; Cerebral Veins; Diagnosis, Differential; Encephalitis, Herpes Simplex; Heparin; Humans; Hydrocephalus; Magnetic Resonance Imaging; Male; Simplexvirus; Superior Sagittal Sinus; Temporal Lobe; Venous Thrombosis; Warfarin

Several cases of herpes simplex encephalitis (HSE) caused by acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) have been reported. Amino acid substitutions of R41H, Q125H, and A156V in the viral thymidine kinase (vTK) gene have been reported to confer ACV resistance. Recombinant HSV-1 clones, containing each amino acid substitution in the vTK gene, were generated using the bacterial artificial chromosome system. A recombinant HSV-1 with the Q125H substitution showed ACV resistance while the R41H or A156V substitutions were ACV-sensitive. Furthermore, the Q125H recombinant HSV-1 was less virulent than the repaired virus, but it maintained neurovirulence in mice at relatively high levels. Substitution of Q125H, which was detected in the neonatal HSE patient, conferred ACV resistance, but the substitutions of R41H and A156V, which were detected in immunocompetent adult HSE patients, did not. This suggests that HSE caused by ACV-resistant HSV-1 might be a very rare event to occur during the course of ACV treatment in immunocompetent patients. Showing resistance to ACV treatment does not always indicate emergence of ACV-resistant HSV-1 in HSE patients.

Topics: Acyclovir; Adult; Aged; Amino Acid Substitution; Animals; Antiviral Agents; Cell Line; Chromosomes, Artificial, Bacterial; Disease Models, Animal; Drug Resistance, Viral; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Infant, Newborn; Male; Mice, Inbred ICR; Microbial Sensitivity Tests; Middle Aged; Mutant Proteins; Reverse Genetics; Thymidine Kinase; Virulence; Virulence Factors

Herpes Simplex Virus encephalitis (HSVE) is a devastating disease of all ages. Rigorous studies correlating viral load with neuroradiological and clinical severity have not been performed, particularly in neonates. Understanding these relationships may improve therapies.. To correlate molecularly quantified HSV in cerebrospinal fluid (CSF) and disease severity.. HSV loads (VL) were evaluated by real-time PCR from the CSF of 33 patients (20 neonates, 5 children, 8 adults) with HSVE. We studied relationships between CSF VL and structural and volumetric brain abnormalities (MRI); hospital morbidity; and discharge and long-term (>3 month) clinical outcomes.. Initial CSF VL did not differ in neonates vs non-neonates (median 4.6 vs 5.1 log10 copies/mL, p = 0.75). Initial CSF VL was higher in neonates with HSV-2 vs HSV-1 (median 4.8 vs 3.2 log10 copies/mL, respectively, p = 0.02). Persistently detectable DNA in CSF despite acyclovir trended towards higher odds of unfavorable outcome at discharge for neonates [0.87 (CI 0.75-1), p = 0.07]. Initial VL correlated with higher CSF protein concentrations for the cohort and for neonates (p = 0.03 and 0.01, respectively), but not with lesion volume or subarachnoid exposure of involved brain (p all >0.05), hospital morbidity (p all >0.05), nor with higher odds of unfavorable discharge or long-term outcomes for the cohort [OR = 0.9(CI 0.5-1.6), p = 0.72; OR = 1.0(CI 0.5-1.8), p = 0.9] or for neonates [OR = 1.3(CI 0.5-3.3), p = 0.57; OR = 2.3(CI 0.7-8), p = 0.2].. Initial HSV VL did not predict neuroradiological or clinical outcomes in patients with HSVE, suggesting host inflammatory factors contribute to disease in treated patients with good viral clearance.

Topics: Acyclovir; Adolescent; Adult; Brain; Child; Child, Preschool; DNA, Viral; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Polymerase Chain Reaction; Severity of Illness Index; Viral Load; Young Adult

This article explains the approach to managing a patient with herpes simplex virus encephalitis. Acute encephalopathy is a common and often intimidating presentation in an acute general medical setting. Application of key principles will enable the generalist to take life-saving action before obtaining any specialist input. Viral infection is the most common cause (48.2%) of encephalitis; another large group is cases of autoimmune aetiology. Early diagnosis of encephalitis is crucial to ensure that the right treatment is given on time. Guidelines on the management of viral encephalitis were published by the British Association of Neurologists and British Infection Association ( Solomon et al, 2012 ), but adherence to these standards by clinicians has been found to be suboptimal ( Han and Coebergh, 2017 ). This puts lives in danger, in the context of a treatable, serious, acute presentation. Although viral infection is the most common cause of encephalitis, an awareness of rarer forms of autoimmune encephalitis is necessary. The differential diagnosis of autoimmune encephalitis is important because the disease is potentially treatable with immunosuppressive agents. Paraneoplastic limbic encephalitis may present months or years before the detection of a tumour.

Topics: Acyclovir; Adult; Antiviral Agents; Diagnosis, Differential; Drug Administration Schedule; Early Diagnosis; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Prognosis

A 70-year-old man developed urinary retention in the early stages of herpes simplex virus (HSV) type-1 encephalitis. A nerve conduction study suggested latent myeloradiculitis. This is the first report of human herpes simplex virus-1 encephalitis followed by urinary retention at early stage from the onset like the Elsberg syndrome. Although relatively few similar cases have been reported, we consider that urinary retention is common in HSV-1 encephalitis, in which disturbances of consciousness usually require bladder catheterization from the onset. We further emphasize that urinary retention may occasionally occur in early stages of HSV-1 encephalitis, with a significant possibility of recovery.

Topics: Acyclovir; Aged; Antiviral Agents; Brain; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Treatment Outcome; Urinary Retention

Topics: Acyclovir; Adolescent; Antiviral Agents; Brain; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Foscarnet; Glasgow Coma Scale; Humans; Magnetic Resonance Imaging; Male; Paresthesia; Treatment Outcome

A 10-day-old child was treated for neonatal herpes simplex virus (HSV) central nervous system (CNS) disease with 21 days of intravenous acyclovir and 6 months of oral acyclovir. She presented 7 years later with HSV CNS disease and new lesions in her brain, illustrating the non-benign nature of delayed recurrent HSV CNS disease.

Topics: Acyclovir; Antiviral Agents; Brain; Child; Encephalitis, Herpes Simplex; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Magnetic Resonance Imaging; Neuroimaging; Recurrence; Simplexvirus

Extravasation of intravenously infused vesicant solutions is a common problem in medical practice, which can lead to severe and progressive tissue dysfunction, ranging from persistent tissue oedema and fibrosis to delayed tissue necrosis. Acyclovir is a known vesicant medication administrated in paediatric patients, which appears to irritate venous and soft tissue if extravasated.. We present the first case involving the extravasation of intravenously infused acyclovir in a female adolescent patient, which caused tissue necrosis and left behind a residual scar lesion. Nursing and medical staff should be aware of the potential dermatological side effects of intravenously infused acyclovir and other medications, even a long time after infusion, and the possible lack of initial local symptoms and signs.. Early recognition of extravasation and prompt management are critical in preventing further morbidity, and optimizing outcomes.

Topics: Acyclovir; Adolescent; Antiviral Agents; Encephalitis, Herpes Simplex; Extravasation of Diagnostic and Therapeutic Materials; Female; Humans; Necrosis

A 73-year-old woman presented with sudden onset of right hemiparesis and was diagnosed as having cerebral infarction on the basis of diffusion-weighted brain MRI, which demonstrated lesions in the left parietal cortex. On the 3rd day, the patient developed right upper limb myoclonus, aphasia, and disturbance of consciousness with high fever. On the 6th day, she was transferred to our hospital with suspected viral encephalitis, and treatment with acyclovir was started. By the 6th day, the lesions detected by MRI had expanded to the gyrus cinguli, insula and thalamus, but not to the temporal lobe. At that time, the CSF cell count was 8/μl, and this later increased to 17/μl by the 13th day. Although herpes simplex virus DNA was detected in the CSF on the 6th day, there was no evidence of CSF pleocytosis or temporal lobe abnormalities demonstrable by brain MRI throughout the whole follow-up period. This was very atypical case of herpes simplex encephalitis characterized by a stroke-like episode, atypical MRI findings, and absence of cerebrospinal fluid pleocytosis. It is important to be mindful that herpes simplex encephalitis (HSE) can have an atypical presentation, and that sufficient acyclovir treatment should be initiated until HSE can be ruled out.

Topics: Acyclovir; Aged; Antiviral Agents; Biomarkers; Brain; Clonazepam; DNA, Viral; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Humans; Leukocytosis; Levetiracetam; Magnetic Resonance Imaging; Methylprednisolone; Neuroimaging; Piracetam; Simplexvirus; Stroke

Topics: Acyclovir; Antiviral Agents; Encephalitis; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Simplexvirus

Topics: Acyclovir; Antiviral Agents; Encephalitis; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Simplexvirus

We report a 57-year-old woman with end-stage renal disease (ESRD) on maintenance peritoneal dialysis (PD), who presented to the emergency room (ER) by ambulance with complaints of confusion and altered sensorium for 48 hours. She had been reviewed in a walk-in clinic 72 hours earlier and had been prescribed the standard 1000 mg three times per day of valacyclovir for an acute attack of shingles instead of 500 mg once a day on ESRD. In the ER, she received further 500 mg of intravenous acyclovir as herpes encephalitis was clinically suspected. CT of the brain and lumbar puncture were non-contributory to the diagnosis. Valacyclovir and acyclovir were discontinued when the diagnosis of valacyclovir-associated neurotoxicity became clinically evident. As the patient's Glasgow Coma Scale declined, we intensified her PD regimen from one to six exchanges per day and 24 hours later there was a significant neurological improvement.

Topics: Acyclovir; Administration, Intravenous; Antiviral Agents; Confusion; Consciousness Disorders; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Herpes Zoster; Humans; Kidney Failure, Chronic; Middle Aged; Neurotoxicity Syndromes; Peritoneal Dialysis; Valacyclovir; Valine

Topics: Acyclovir; Aged; Anti-Inflammatory Agents; Antiviral Agents; Confusion; Encephalitis, Herpes Simplex; Fever; Humans; Magnetic Resonance Imaging; Male; Nausea; Prednisolone; Retinal Detachment; Spinal Puncture; Treatment Outcome; Vitrectomy

Herpes simplex virus 1 (HSV) encephalitis (HSE) has serious neurological complications, involving behavioral and cognitive impairments that cause significant morbidity and a reduced quality of life. We showed that HSE results from dysregulated central nervous system (CNS) inflammatory responses. We hypothesized that CNS inflammation is casually involved in behavioral abnormalities after HSE and that treatment with ACV and pooled human immunoglobulin (IVIG), an immunomodulatory drug, would improve outcomes compared to mice treated with phosphate buffered saline (PBS) or ACV alone. Anxiety levels were high in HSV-infected PBS and ACV-treated mice compared to mice treated with ACV + IVIG, consistent with reports implicating inflammation in anxiety induced by lipopolysaccharide (LPS) or stress. Female, but not male, PBS-treated mice were cognitively impaired, and unexpectedly, ACV was protective, while the inclusion of IVIG surprisingly antagonized ACV's beneficial effects. Distinct serum proteomic profiles were observed for male and female mice, and the antagonistic effects of ACV and IVIG on behavior were paralleled by similar changes in the serum proteome of ACV- and ACV + IVIG-treated mice. We conclude that inflammation and other factors mediate HSV-induced behavioral impairments and that the effects of ACV and IVIG on behavior involve novel mechanisms.

Topics: Acyclovir; Animals; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Immunoglobulins, Intravenous; Male; Mice; Mice, Inbred C57BL

Dosing of intravenous acyclovir for herpes encephalitis in obese patients is recommended to be based on ideal body weight. However, limited data support this recommendation, and recent data suggest this may lead to underdosing.. To determine national dosing practices of intravenous acyclovir across a range of patient weights.. A survey was distributed to members of the American College of Clinical Pharmacy Critical Care and Infectious Diseases Practice & Research Networks listservs. Data collected included demographic information and dosing of acyclovir, given consistent patient cases with varying patient weight.. A total of 264 pharmacists participated in the survey, with 240 (90.9%) participants completing the survey. Participants were predominately clinical pharmacists. As patient weight increased, respondents were more apt to dose based on an adjusted body weight, with dosing in the obese and morbidly obese showing a clear lack of consistency.. Intravenous dosing of acyclovir for herpes encephalitis is variable, especially in obese patients, and does not reflect recommendations. Limited data provide conflicting recommendations for dosing in obese patients, and future studies are necessary to optimize patient outcomes and prevent toxicity.

Topics: Acyclovir; Administration, Intravenous; Antiviral Agents; Body Weight; Encephalitis, Herpes Simplex; Female; Humans; Male; Obesity; Pharmacists; Surveys and Questionnaires

Consensus treatment for herpetic meningoencephalitis is intravenous aciclovir but no guidelines are available for alternative treatment in case of renal failure induced by aciclovir. We report to the best of our knowledge, the first case of herpetic meningoencephalitis treated with success by ganciclovir.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Ganciclovir; Humans; Male; Middle Aged

Topics: Acyclovir; Adult; Antiviral Agents; Cerebral Cortex; Encephalitis; Encephalitis, Herpes Simplex; Humans; Immunocompromised Host; Magnetic Resonance Imaging; Male; Middle Aged

Acyclovir resistance is rarely seen in herpes simplex virus (HSV) type I encephalitis. Prevalence rates vary between 0.5 % in immunocompetent patients (Christophers et al. 1998; Fife et al. 1994) and 3.5-10 % in immunocompromised patients (Stranska et al. 2005). We report a 45-year-old, immunocompetent (negative HIV antigen/antibody testing), female patient, without previous illness who developed-after a febrile prodromal stage-aphasia and psychomotor slowing. Cerebral magnetic resonance imaging (cMRI) showed right temporal and insular T2-hyperintense lesions with spreading to the contralateral temporal lobe. Cerebrospinal fluid (CSF) analysis yielded lymphocytic pleocytosis and elevated protein level. Polymerase chain reaction testing for HSV type I showed a positive result in repeat lumbar puncture. HSV type I encephalitis was diagnosed and intravenous acyclovir treatment was initiated (750 mg t.i.d.). Acyclovir treatment was intensified to 1000 mg t.i.d., due to clinical deterioration, ongoing pleocytosis and progression on cMRI 5 days after initiation of antiviral therapy. In parallel, acyclovir resistance testing showed mutation of thymidine kinase gene at position A156V prompting foscarnet therapy (60 mg t.i.d.). Patient's condition improved dramatically over 2 weeks. Acyclovir resistance is rare but should be considered in case of clinical worsening of patient's condition. To our knowledge, this is the first report of acyclovir resistance in HSV type I encephalitis of an immunocompetent and previously healthy patient in Austria.

Topics: Acyclovir; Antiviral Agents; Disease Progression; Drug Resistance, Viral; Drug Substitution; Encephalitis, Herpes Simplex; Female; Foscarnet; Herpes Simplex; Herpesvirus 1, Human; Humans; Leukocytosis; Magnetic Resonance Imaging; Middle Aged; Temporal Lobe

Morbidity and mortality of Herpes simplex virus encephalitis (HSE) remain high. Relapses of neurological signs may occur after initial clinical improvement under acyclovir treatment.. We report here a case of post-HSE anti-N-methyl-d-aspartate receptor-mediated encephalitis in an adult and perform a systematic search on PubMed to identify other cases in adults.. We identified 11 previously published cases, to discuss diagnostic and therapeutic management. Symptoms in adults are often inappropriate behaviors, confusion and agitation. Diagnosis of anti-NMDA-R encephalitis after HSE is often delayed. Treatment consists in steroids, plasma exchange, and rituximab. Prognosis is often favorable.. Anti-NMDA-R antibodies should be searched in cerebrospinal fluid of patients with unexpected evolution of HSE. This emerging entity reopens the hot debate about steroids in HSE.

Topics: Acyclovir; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antiviral Agents; Communicable Diseases, Emerging; Encephalitis, Herpes Simplex; Female; France; Humans; Middle Aged; Recurrence

It is unclear whether immunosuppression is a risk factor for herpes encephalitis. Herein, we describe a rare case of herpes simplex virus type 2 encephalitis in a patient treated with low-dose methotrexate for HLA-B27-associated spondyloarthritis. The patient was successfully treated with acyclovir but presented sequelae of encephalitis. Here we discuss the possible role of low-dose methotrexate therapy as a risk factor of neurological herpes reactivation and severe disease. The host-related and viral risk factors are also addressed.

Topics: Acyclovir; Aged; Antiviral Agents; Contraindications, Drug; Encephalitis, Herpes Simplex; Gene Expression; HLA-B27 Antigen; Humans; Immunosuppressive Agents; Male; Methotrexate; Risk Factors; Spondylitis, Ankylosing

Herpes simplex encephalitis (HSE) can be complicated by adverse events in the acute phase. We herein present the case of a 71-year-old woman with HSE complicated by cerebral hemorrhage. She presented with acute deterioration of consciousness and fever and was diagnosed with HSE based on the detection of herpes simplex virus-1 in the cerebrospinal fluid by a polymerase chain reaction. The cerebral hemorrhage developed during acyclovir therapy; however, its diagnosis was delayed for 2 days. After the conservative treatment of the cerebral hemorrhage, the patient made a near-complete recovery. Cerebral hemorrhage should be considered as an acute-phase complication of HSE.

Topics: Acyclovir; Aged; Antiviral Agents; Cerebral Hemorrhage; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Fever; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed

We describe corticosteroid-responsive focal granulomatous encephalitis as a manifestation of herpes simplex virus (HSV) type 1 disease in the brain: something easily missed and easily treated. Two adult cases presented with cognitive symptoms progressing over weeks, despite aciclovir treatment. Brain imaging showed temporal lobe abnormalities, with gadolinium enhancement but no abnormal diffusion restriction. HSV-1 PCR analysis was negative in cerebrospinal fluid (CSF) but positive in brain biopsies, which showed vasocentric granulomatous inflammation. Paired blood and CSF samples showed intrathecal synthesis of HSV-1 type-specific IgG. The patients improved clinically only after immunosuppression. Despite profound cognitive impairment at their clinical nadir, both patients recovered fully. We suggest that, at least in a subset of patients with HSV-1 encephalitis, adjunctive corticosteroid treatment is critical to improve the outcome of the disease.

Topics: Acyclovir; Adrenal Cortex Hormones; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Middle Aged

Herpes simplex virus (HSV) infections of the central nervous system (CNS) are associated with significant morbidity and mortality rates in children. This study assessed the impact of a direct HSV (dHSV) PCR assay on the time to result reporting and the duration of acyclovir therapy for children with signs and symptoms of meningitis and encephalitis. A total of 363 patients with HSV PCR results from cerebrospinal fluid (CSF) samples were included in this retrospective analysis, divided into preimplementation and postimplementation groups. For the preimplementation group, CSF testing was performed using a laboratory-developed real-time PCR assay; for the postimplementation group, CSF samples were tested using a direct sample-to-answer assay. All CSF samples were negative for HSV. Over 60% of patients from both groups were prescribed acyclovir. The average HSV PCR test turnaround time for the postimplementation group was reduced by 14.5 h (23.6 h versus 9.1 h;

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Central Nervous System; Cerebrospinal Fluid; Child; Child, Preschool; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Infant, Newborn; Male; Meningitis; Real-Time Polymerase Chain Reaction; Retrospective Studies; Young Adult

Herpes simplex virus (HSV) encephalitis can induce an autoimmune encephalitis mediated by autoantibodies against the N-methyl-D-aspartate receptor (NMDAR). Post-HSV NMDAR encephalitis and de novo NMDAR encephalitis have been more commonly described in children and young adults. We describe the case of a 67-year-old woman with post-HSV NMDAR encephalitis and review the relevant literature. Clinical, serological, neurophysiological, and imaging evaluations were undertaken in the evaluation of this patient. A literature review was performed. Nearly 2 months after a typical course of HSV encephalitis confirmed by HSV polymerase chain reaction studies from the spinal fluid and treated with intravenous acyclovir, a 67-year-old woman suffered neurological deterioration. There was no evidence of active HSV infection, but NMDAR antibodies were found in her serum and spinal fluid. The patient improved after initiation of immunosuppressive therapy. All patients who experience new or recurrent neurological symptoms following recovery from HSV encephalitis should be evaluated for post-infectious autoimmune encephalitis, including NMDAR encephalitis.

Topics: Acyclovir; Aged; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antiviral Agents; Autoantibodies; DNA-Directed DNA Polymerase; Encephalitis, Herpes Simplex; Female; Gene Expression; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Rituximab; Simplexvirus; Viral Proteins

Topics: Acyclovir; Antiviral Agents; Corpus Callosum; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Humans; Magnetic Resonance Imaging; Meningitis, Viral; Middle Aged; Treatment Outcome

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Infant, Newborn; Infant, Premature; Perinatal Care; Pregnancy; Pregnancy Complications, Infectious; Premature Birth

Topics: Acyclovir; Antineoplastic Agents, Alkylating; Antiviral Agents; Brain Stem Neoplasms; Cognitive Dysfunction; Cranial Irradiation; Dacarbazine; Delirium; Dexamethasone; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Glioma; Herpesvirus 1, Human; Humans; Leukocytosis; Magnetic Resonance Imaging; Seizures; Temozolomide; Young Adult

Topics: Acyclovir; Adrenal Cortex Hormones; Anti-Bacterial Agents; Antiviral Agents; Brain Neoplasms; Ceftriaxone; Dexamethasone; Diagnosis, Differential; Electroencephalography; Emergency Service, Hospital; Encephalitis, Herpes Simplex; Fever; Humans; Hypnotics and Sedatives; Infarction; Levetiracetam; Male; Massachusetts; Middle Aged; Phenytoin; Piracetam; Propofol; Status Epilepticus; Temporal Lobe; Tomography, X-Ray Computed; Unconsciousness; Vancomycin

Herpes simplex virus (HSV) encephalitis is a potentially devastating disease, with significant rates of mortality and co-morbidities. Although the prognosis for people with HSV encephalitis can be improved by prompt treatment with aciclovir, there are often delays involved in the diagnosis and treatment of the disease. In response, National Clinical Guidelines have been produced for the UK which make recommendations for improving the management of suspected viral encephalitis. However, little is currently known about the everyday experiences and processes involved in the diagnosis and care of HSV encephalitis. The reported study aimed to provide an account of the diagnosis and treatment of HSV encephalitis from the perspective of people who had been affected by the condition. Thirty narrative interviews were conducted with people who had been diagnosed with HSV encephalitis and their significant others. The narrative accounts reveal problems with gaining access to a diagnosis of encephalitis and shortfalls in care for the condition once in hospital. In response, individuals and their families work hard to obtain medical recognition for the problem and shape the processes of acute care. As a consequence, we argue that the diagnosis and management of HSV encephalitis needs to be considered as a participatory process, which is co-produced by health professionals, patients, and their families. The paper concludes by making recommendations for developing the current management guidelines by formalising the critical role of patients and their significant others in the identification, and treatment of, HSV encephalitis.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Male; Middle Aged; Young Adult

Systemic chemotherapy combined with steroids used as prophylactic antiemetics have been reported to induce immunosuppression. Further, herpes simplex virus-1 (HSV-1) infection has been reported to occur in patients with small cell carcinomas after chemoradiotherapy that includes brain irradiation. Here, we report a case of HSV-1 encephalitis that occurred in a patient undergoing chemoradiotherapy for advanced esophageal cancer.. A 77-year-old woman received chemoradiotherapy (5-fluorouracil, 700 mg/m(2); cisplatin, 70 mg/m(2); and radiotherapy, 60 Gy in total) for stage III esophageal cancer. The total radiation dose was administered concurrently with the first two courses of chemotherapy, together with dexamethasone as a prophylactic antiemetic. Two days before completion of the fourth course of chemotherapy, the patient developed acute neurological symptoms of disorientation, clouding of consciousness, and fever. T2-weighted magnetic resonance imaging showed a high intensity area in the bilateral temporal lobes and insular cortex. Furthermore, DNA PCR testing of cerebrospinal fluid showed clear positivity for HSV-1 DNA, and the patient was diagnosed with herpetic encephalitis. Intravenous administration of acyclovir for 3 weeks led to gradual improvement of consciousness, and the patient was able to respond to verbal cues.. In advanced esophageal cancer patients, standard treatment involves chemoradiotherapy and surgery. However, primary infection with or reactivation of endogenous latent HSV-1 in the brain cortex during chemoradiotherapy combined with administration of a steroid may compromise the benefits of treatment.

Topics: Acyclovir; Aged; Chemoradiotherapy; Cisplatin; Dexamethasone; Encephalitis, Herpes Simplex; Esophageal Neoplasms; Female; Fluorouracil; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Steroids

Topics: Acyclovir; Adult; Anticonvulsants; Antiviral Agents; Brain; Brain Edema; Confusion; Diuretics, Osmotic; DNA, Viral; Encephalitis, Herpes Simplex; Fever; Herpesvirus 1, Human; Humans; Male; Mannitol; Polymerase Chain Reaction; Seizures; Temporal Lobe; Tomography, X-Ray Computed

Herpes simplex encephalitis (HSE) is a life-threatening complication of herpes simplex virus (HSV) infection. Acyclovir (ACV) is the antiviral treatment of choice, but may lead to emergence of ACV-resistant (ACVR) HSV due to mutations in the viral UL23 gene encoding for the ACV-targeted thymidine kinase (TK) protein. Here, we determined the prevalence of intrathecal ACVR-associated HSV TK mutations in HSE patients and compared TK genotypes of sequential HSV isolates in paired cerebrospinal fluid (CSF) and blister fluid of mucosal HSV lesions. Clinical samples were obtained from 12 HSE patients, encompassing 4 HSV type 1 (HSV-1) and 8 HSV-2 encephalitis patients. HSV DNA load was determined by real-time PCR and complete HSV TK gene sequences were obtained by nested PCR followed by Sanger sequencing. All HSV-1 HSE patients contained viral TK mutations encompassing 30 unique nucleotide and 13 distinct amino acid mutations. By contrast, a total of 5 unique nucleotide and 4 distinct amino acid changes were detected in 7 of 8 HSV-2 patients. Detected mutations were identified as natural polymorphisms located in non-conserved HSV TK gene regions. ACV therapy did not induce the emergence of ACVR-associated HSV TK mutations in consecutive CSF and mucocutaneous samples of 5 individual patients. Phenotypic susceptibility analysis of these mucocutaneous HSV isolates demonstrated ACV-sensitive virus in 2 HSV-1 HSE patients, whereas in two HSV-2 HSE patients ACVR virus was detected in the absence of known ACVR-associated TK mutations. In conclusion, we did not detect intrathecal ACVR-associated TK mutations in HSV isolates obtained from 12 HSE patients.

Topics: Acyclovir; Adult; Amino Acid Substitution; Antiviral Agents; Demography; Drug Resistance, Viral; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Prevalence; Spinal Cord; Thymidine Kinase; Young Adult

Topics: Acyclovir; Adult; Antiviral Agents; Early Diagnosis; Encephalitis, Herpes Simplex; Father-Child Relations; Fathers; Female; Gestures; Herpes Labialis; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Male

Herpes simplex virus encephalitis (HSE) is a significant cause of morbidity and mortality. Neurologic sequelae are common even after early initiation of acyclovir treatment. The host immune response during HSE can also lead to brain damage. There are an increasing number of reports favoring steroid use in HSE.. We aimed to compare the prognosis of children with HSE with and without steroid therapy.. We retrospectively screened our hospital archive from 2009 to 2014 for patients diagnosed with HSE with a positive result for herpes simplex virus polymerase chain reaction in cerebrospinal fluid. Patients ≥1 month and ≤18 years at diagnosis were included in the study. Clinical outcomes in terms of cognitive function, motor function, electroencephalographic findings, seizure frequency, and radiologic findings were compared in patients who received adjuvant steroid therapy with those who did not.. Six patients (1 boy, 5 girls; aged 4 months to 10 years) were included. Overall symptom duration before hospital admission was ≤5days. Patients received acyclovir treatment for 21-28days. Three received steroid therapy early during the disease and three patients did not. No adverse effects related to steroids were observed. Follow-up duration was 6 months to 5 years. All patients had radiologic sequelae of encephalitis. Cognition, motor function, and seizure control were better in patients who received steroid therapy.. Adjuvant steroid therapy seems to be effective in decreasing morbidity in children with HSE but the radiologic sequelae were the same in both groups.

Topics: Acyclovir; Antiviral Agents; Brain; Cerebrospinal Fluid; Child; Child, Preschool; Cognition; Encephalitis, Herpes Simplex; Female; Humans; Infant; Male; Retrospective Studies; Simplexvirus; Treatment Outcome

A 78-year-old woman was diagnosed with bullous pemphigoid 2 months ago, and she had been treated with steroid and plasmapheresis. She developed sudden fever, vomiting, disorientation, and abnormal behavior. Diffusion weighted images and fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images showed high-intensity signals in the right temporal lobe hippocampus and right insular cortex. Cerebrospinal fluid (CSF) examination showed normal cell count (4/mm(3)), but was positive for HSV1-DNA by PCR. She was diagnosed with herpes simplex encephalitis (HSE), and acyclovir was started on the first day of admission. She had complete recovery, and was discharged. She didn't show CSF pleocytosis throughout her course of HSE. No CSF pleocytosis could be due probably to her immunosuppressed state under the steroid therapy for bullous pemphigoid. Because the morbidity and mortality of HSE is drastically reduced by early antiviral treatment, it is important to accelerate the diagnosis and treatment of HSE, especially in immunosuppressed or immunocompromised hosts.

Topics: Acyclovir; Administration, Oral; Aged; Antiviral Agents; Biomarkers; Cerebrospinal Fluid; DNA, Viral; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Hippocampus; Humans; Immunocompromised Host; Magnetic Resonance Imaging; Pemphigoid, Bullous; Prednisolone; Treatment Outcome

To investigate the prevalence and temporal development of N-methyl-d-aspartate receptor (NMDAR) autoantibodies in relation to neurocognitive performance in patients with herpes simplex encephalitis (HSE).. This prospective observational study enrolled a total of 49 HSE patients within a randomized controlled trial of valacyclovir. Cerebrospinal fluid and serum samples were drawn in the initial stage of disease, after 2 to 3 weeks and after 3 months. Anti-NMDAR IgG was detected with HEK293 cells transfected with plasmids encoding the NMDA NR1 type glutamate receptor. A batch of neurocognitive tests, including the Mattis Dementia Rating Scale (MDRS), Glasgow Coma Scale (GCS), Reaction Level Scale (RLS85), Mini-Mental State Examination (MMSE) and National Institutes of Health (NIH) stroke scale, was performed during 24 months' follow-up.. Anti-NMDAR IgG was detected in 12 of 49 participants. None were antibody positive in the initial stage of disease. In ten of 12 positive cases, specific antibodies were detectable only after 3 months. Notably, the development of NMDAR autoantibodies was associated with significantly impaired recovery of neurocognitive performance. After 24 months' follow-up, the median increase in MDRS total score was 1.5 vs. 10 points in antibody-positive and -negative participants (p=0.018).. Anti-NMDAR autoimmunity is a common complication to HSE that develops within 3 months after onset of disease. The association to impaired neurocognitive recovery could have therapeutical implications, as central nervous system autoimmunity is potentially responsive to immunotherapy.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Autoantibodies; Encephalitis, Herpes Simplex; Female; HEK293 Cells; Humans; Male; Middle Aged; Neuropsychological Tests; Prospective Studies; Receptors, N-Methyl-D-Aspartate; Sweden; Valacyclovir; Valine

Incidence of brain infections in Human Immunodeficiency Virus (HIV) positive patients is reduced after the availability of current high active antiretroviral therapy (HAART). Herpes Simplex Virus type 2 (HSV-2) is an infrequent cause of encephalitis in HIV patients despite it is frequently involved in sexual transmitted infections. Here, we report a case of HSV-2 encephalitis occurring in a patient without full suppression of HIV replication within the brain. A 38 year-old HIV infected man was admitted to our department because of recurrent generalized seizure and fever during the previous 24 hours. Eight months before our observation the patient was switched from a protease inhibitor based regimen to a rilpivirine-based regimen without any evidence of HIV-RNA replication in the plasma. When the patient was admitted in our hospital, he was febrile and moderately confused, no deficit of cranial nerves was reported, motility was conserved, but he was unable to walk. Laboratory examinations performed at admission demonstrated an increase of cerebrospinal fluid (CSF) protein and cells with lymphocyte prevalence, and normal CSF glucose. HSV-2-DNA and HIV-RNA were present within CSF at admission. Nuclear Magnetic Resonance imaging of the brain revealed lesions of the medial part of both temporal lobes including hippocampus without any sign of bleeding. A 21-day course of acyclovir therapy was administered with consistent improvement of clinical findings and disappearance of HSV-2-DNA within CSF. After the episode, HAART was switched to a regimen with high CSF penetrability containing abacavir, lamivudine, darunavir and ritonavir. Twelve months after HSV-2 encephalitis neurologic evaluation was normal, but symptoms of depression were reported, HIV-RNA remained undetectable both in the plasma and CSF, and CD4+ lymphocytes were above 500/μL. No opportunistic infection was reported. Patients switched to regimen well tolerated such those containing rilpivirine, that have poor drug concentration within CSF could be considered at risk for opportunistic infection of the brain. Further larger investigation needs to confirm this finding.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; Darunavir; Dideoxynucleosides; Drug Substitution; Encephalitis, Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV Protease Inhibitors; Humans; Lamivudine; Male; Rilpivirine; Ritonavir; Virus Replication

Herpes simplex virus encephalitis (HSE) is a rare but often fatal disease if left untreated. MRI typically shows the characteristic findings of medial temporal lobe and insular involvement, while diagnosis in confirmed by CSF PCR. In immunocompromised state, HSE may have atypical clinical and radiological features. We report a MS patient under natalizumab treatment with HSE, who presented with MRI lesions exclusively in the right parietal lobe. The patient was timely started on acyclovir resulting in marked improvement. A high index of suspicion for HSE should be maintained when a patient presents with fever and extratemporal lesions, even more in immunocompromised subjects.

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Humans; Immunologic Factors; Male; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Parietal Lobe

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are important causes of acute neurologic illness. Although the role of acyclovir in treating HSV encephalitis is clear, the role of antiviral therapy in HSV meningitis remains controversial.. In this retrospective observational study, we reviewed the charts of all patients with cerebrospinal fluid specimens positive for HSV-1 or HSV-2 by polymerase chain reaction between July 2000 and November 2012. Patients' charts were reviewed for demographic data, clinical presentation, treatment, and clinical outcomes.. Forty-two patient-episodes were clinically classified as meningitis. In 6 episodes (14.3%), patients with meningitis received no antivirals, whereas the remaining episodes were treated with an oral antiviral (n = 11 [26.2%]), combination intravenous and oral therapy (n = 22 [52.4%]), or intravenous acyclovir alone (n = 3 [7.1%]). Six patients had recurrent episodes of meningitis and all recovered without any neurologic sequelae. Neurologic outcomes were significantly improved with antiviral therapy in immunocompromised patients with herpes meningitis (P < .05), but not in the 27 patient-episodes among immunocompetent patients (P = 1.0), as no neurologic sequelae were noted in this group.. Most patients with HSV meningitis rapidly improve, but immunocompromised hosts have more neurologic sequelae and may benefit from antiviral therapy. Our data suggest symptomatic treatment alone for immunocompetent patients with HSV meningitis, avoiding the cost and side effects of prolonged intravenous acyclovir therapy; in contrast, immunocompromised patients had improved outcomes and would therefore benefit from antiviral therapy.

Topics: Acyclovir; Adult; Antiviral Agents; Cerebrospinal Fluid; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Immunocompromised Host; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; Encephalitis, Herpes Simplex; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Piloerection; Polymerase Chain Reaction; Spinal Puncture

A cluster of children receiving intravenous (IV) acyclovir for meningoencephalitis developed acute renal failure in April-May 2008, which prompted a retrospective case-control study to determine the rate of and risk factors for acute nephrotoxicity during IV acyclovir treatment in children.. The percentage decrease in glomerular filtration rate in children receiving IV acyclovir who had ≥ 1 creatinine measurement after acyclovir initiation from October 2006 to January 2009 was classified as renal risk, injury, or failure according to modified Pediatric Risk Injury, Failure, Loss, End-Stage Renal Disease criteria. Univariate and multivariate matched analyses were conducted to identify risk factors contributing to nephrotoxicity.. In the selected study group, renal dysfunction was seen in 131 of 373 (35%) treatment courses studied: 81 of 373 (22%) risk, 36 of 373 (9.7%) injury, and 14 of 373 (3.8%) failure. Most renal dysfunction occurred within 48 hours of the initiation of acyclovir. Renal function returned to the normal range but not to baseline in most cases during the follow-up period. Risk factors for renal dysfunction included acyclovir dose >15 mg/kg (OR 3.81, 95% CI 1.55-9.37) for risk; cumulative exposure greater than calculated cumulative exposure based on 500 mg/m(2)/dose (OR 6.00, 95% CI 1.95-18.46) for injury; and age >8 years (OR 21.5, 95% CI 2.2, >1000) and ceftriaxone coadministration (OR 19.3, 95% CI 1.8, >1000) for failure.. Nephrotoxicity associated with IV acyclovir is common and necessitates renal function monitoring. Risk factors include greater dose, older age, and concomitant ceftriaxone administration. Outside the neonatal period, renal dysfunction may be minimized by dosing IV acyclovir below thresholds associated with nephrotoxicity (ie, ≤ 500 mg/m(2)/dose or ≤ 15 mg/kg/dose), particularly in older patients.

Topics: Acute Kidney Injury; Acyclovir; Adolescent; Antiviral Agents; Case-Control Studies; Child; Child, Preschool; Encephalitis, Herpes Simplex; Encephalitis, Varicella Zoster; Female; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Male; Retrospective Studies; Risk Factors; Young Adult

We report a rare case of relapsing herpes simplex encephalitis in a-37-year-old patient which was previously confirmed by positive polymerase chain reaction, herpes simplex virus (HSV) type1 IgG antibodies in cerebrospinal fluid and characterized on MRI. During the first admission, he was treated with continuous acyclovir treatment for one month with clinical improvement except for residual aphasia, for which he received a course of outpatient transcranial direct current stimulation (tDCS). A constant current of 1.2 mA was applied for 20 min twice daily. After the 4th day the patient was found to be irritable and uncooperative by staff and family members. A subsequent MRI showed significant deterioration of the lesion on comparison to the first MRI which led to discontinuation of tDCS.The relatively rapid exacerbation of HSV in only a few days is unusual. Our aim is to discuss if tDCS is related to HSV relapse and in doing so highlight possible mechanisms.

Topics: Acyclovir; Adult; Antiviral Agents; Aphasia; Brain; Electroencephalography; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Male; Polymerase Chain Reaction; Recurrence; Transcranial Direct Current Stimulation

Topics: Acyclovir; Adult; Antiviral Agents; Diffusion Magnetic Resonance Imaging; Encephalitis, Herpes Simplex; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Male; Valine

N-methyl-D-aspartate receptor antibodies (NMDAR-Abs) can contribute to neurological relapse after herpes simplex virus encephalitis (HSE). We describe a child with NMDAR-Ab encephalitis after HSE, which was recognized and treated early. We discuss the case in the context of existing reports, and we propose a modified immunotherapy strategy to minimize risk of viral reactivation.

Topics: Acyclovir; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antiviral Agents; Autoantibodies; Clonidine; Diazepam; Encephalitis, Herpes Simplex; Encephalomalacia; Female; Fever; Humans; Immunocompromised Host; Immunosuppression Therapy; Infant; Leukoencephalopathies; Movement Disorders; Neurological Rehabilitation; Pakistan; Paresis; Phenobarbital; Phenytoin; Plasmapheresis; Receptors, N-Methyl-D-Aspartate; Seizures; Trihexyphenidyl; United Kingdom; Valproic Acid

Herpes simplex encephalitis is rarely caused by herpes simplex virus type 2 (HSV-2) after the neonatal period. The pathogenesis of HSV-2 encephalitis is not known and its treatment has not been discussed. We report a case of mild meningoencephalitis secondary to HSV-2 primary infection after sexual risk behaviour in a healthy young man. The diagnosis was established upon clinical, biological and electroencephalographic criteria. Aciclovir treatment led to rapid clinical improvement. This case highlights HSV-2 as a rare cause of meningoencephalitis, and questions the management of this rare manifestation of HSV-2 infection.

Topics: Acyclovir; Adult; Antibodies, Viral; Antiviral Agents; Brain; Encephalitis, Herpes Simplex; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; Humans; Immunocompetence; Male; Meningoencephalitis; Polymerase Chain Reaction; Radiography

Herpes simplex encephalitis is a severe neurological condition, whose outcome is improved if treated early with acyclovir. Post-herpes simplex encephalitis with acute chorea has rarely been reported.. We report on two observations of children presenting with post-herpes simplex encephalitis with acute chorea, related to two different pathophysiological mechanisms. The first one is an 11-month-old girl developing relapsing herpes simplex encephalitis with chorea due to resumption of viral replication. The second one is a 2-year-old boy with relapsing post-herpes simplex encephalitis acute chorea caused by an immunoinflammatory mechanism. We discuss the different neurological presentations of herpetic relapses, notably those presenting with movement disorders, as well as their clinical, paraclinical, physiopathological, and therapeutic aspects.. Post-herpes simplex encephalitis with acute chorea may involve two mechanisms: resumption of viral replication or an immunoinflammatory mechanism. Treatment of post-herpes simplex encephalitis with acute chorea depends on the underlying mechanism, while prevention is based on antiviral treatment of herpes simplex encephalitis with acyclovir at the dose of 20mg/kg/8h for 21 days.

Topics: Acyclovir; Antiviral Agents; Child; Child, Preschool; Chorea; Consanguinity; Encephalitis, Herpes Simplex; Female; Humans; Male; Recurrence; Risk Factors; Treatment Outcome

A 74-year-old man presented with acute right-sided hemiparesis and epilepsia partialis continua in association with fever and confusion. Initial workup revealed possible cerebritis in the left medial frontal lobe without involvement of the temporal lobes. Cerebrospinal fluid (CSF) analysis revealed minimal lymphocytic pleocytosis but negative real-time herpes simplex virus (HSV) PCR. Acyclovir was discontinued on day 5 due to a negative infectious workup and clinical improvement. On day 9 his condition deteriorated and he was transferred to a higher level of acuity for advanced supportive care. Worsening encephalopathy and refractory status epilepticus ensued despite medical care. Repeat CSF analysis showed mild lymphocytic pleocytosis with negative real-time HSV PCR. Brain MRI revealed progression of cortical enhancement. Immunosuppressive therapy and plasma exchange were attempted without clinical response. On day 24, another lumbar puncture showed only mild lymphocytic pleocytosis. Brain MRI showed involvement of the right medial temporal lobe. Subsequently, acyclovir was resumed. The HSV-1 PCR result was positive on day 30. Unfortunately, the patient expired.

Topics: Acyclovir; Aged; Antiviral Agents; Brain; Confusion; DNA, Viral; Encephalitis; Encephalitis, Herpes Simplex; Epilepsia Partialis Continua; False Negative Reactions; Fatal Outcome; Fever; Herpesvirus 1, Human; Humans; Leukocytosis; Magnetic Resonance Imaging; Male; Real-Time Polymerase Chain Reaction

Despite antiviral therapy, the mortality rate of herpes simplex virus encephalitis (HSE) remains high and many surviving patients harbor neurological sequelae. Although viral replication is responsible for substantial neurological damages, an exaggerated inflammatory response could also contribute to this process. Artesunate (ART) and rapamycin (RAPA) have shown some benefits in the treatment of herpes simplex virus infections. Herein, we evaluated the benefit of combining ART or RAPA with valacyclovir (VACV) in a murine model of HSE. Infected mice were treated with VACV (1mg/mL in drinking water) from day 3 post-infection (p.i.) combined or not with daily intraperitoneal administration of ART (30mg/kg) or RAPA (20mg/kg) from days 4 to 13 p.i. Viral load, infectious titers, cytokine and chemokine levels were measured in brain homogenates on days 5, 7 and 9. The survival rates of mice treated with VACV and ART or RAPA were higher than with VACV alone (71.9% versus 43.2% for ART and 66.7% versus 43.2% for RAPA; both P⩽0.05) but no significant difference was seen in the brain viral loads. Levels of IL-1β, IL-2 (both P⩽0.05), IL-6, IFN-γ (both P⩽0.01), CCL2 (P⩽0.01), CCL3 and CCL4 (both P⩽0.05) were reduced in mice treated with VACV combined with ART versus VACV alone. Levels of IL-6, IL-1β and IFN-γ slightly increased on day 7 in mice treated with VACV combined with RAPA compared to VACV alone and then decreased on day 9. Our results suggest that immunomodulatory compounds such as ART or RAPA could benefit antiviral therapy in HSE.

Topics: Acyclovir; Administration, Oral; Animals; Antiviral Agents; Artemisinins; Artesunate; Brain; Cytokines; Disease Models, Animal; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Immunologic Factors; Injections, Intraperitoneal; Mice, Inbred BALB C; Sirolimus; Survival Analysis; Treatment Outcome; Valacyclovir; Valine; Viral Load

Topics: Acyclovir; Antiviral Agents; Cerebrospinal Fluid; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Herpesviridae; Herpesviridae Infections; Humans; Polymerase Chain Reaction; Schizophrenia; Schizophrenic Psychology; Spirituality; Young Adult

Human herpesviruses cause various acute, subacute, and chronic disorders of the central nervous system and peripheral nervous systems in adults and children. The objective of the present study is to summarize the experience gained with the estimation of viral load in the central nervous system of children and adults with herpes simplex encephalitis (HSE) admitted to a neurological institute at Nagpur, India, by quantitative real-time PCR (qPCR) assay within the past 4 years.. The qPCR assay was evaluated retrospectively in 242 cerebrospinal fluid (CSF) samples from patients. Evaluation of possible relationships was done between the herpes simplex virus (HSV) DNA concentration in CSF with that of patients' clinical and laboratory manifestations. The prevalence of the type of HSV in the study population was also determined using type-specific real-time PCR analysis.. Real-time analysis using type-specific primers revealed the presence of predominantly HSV-1 genotype in the study population. The qPCR results show that in patients with higher viral loads in their CSF, a greater number of cases were associated with the presence of lesions in the brain as revealed by computed tomography/magnetic resonance imaging scan. They required acyclovir therapy for a longer duration and had a poorer clinical outcome than the patients with lower viral loads in their CSF.

Topics: Acyclovir; Adolescent; Adult; Aged; Brain; Cerebrospinal Fluid; Child, Preschool; Encephalitis, Herpes Simplex; Female; Humans; India; Infant; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Retrospective Studies; Simplexvirus; Tomography, X-Ray Computed; Treatment Outcome; Viral Load; Young Adult

Topics: Acyclovir; Antiviral Agents; Confusion; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Middle Aged

Herpes simplex virus is the most common cause of severe sporadic encephalitis. We report a case of herpes simplex type 1-encephalitis in a 50-year-old woman receiving anti-tumor necrosis factor-α monoclonal antibodies adalimumab. Although she was an acyclovir naïve patient, a mixed viral population (wild-type and acyclovir-resistant bearing a thymidine-kinase mutation) was identified in the cerebrospinal fluid. The virus in cerebrospinal fluid evolved and a second thymidine-kinase mutant virus emerged. Combined foscavir and acyclovir treatment resolved the herpes simplex encephalitis. To our knowledge, this is the first report of acyclovir-resistant herpes simplex encephalitis in a patient treated with adalimumab.

Topics: Acyclovir; Adalimumab; Antibodies, Monoclonal, Humanized; Cerebrospinal Fluid; Drug Resistance, Viral; Encephalitis, Herpes Simplex; Female; Foscarnet; Humans; Immunosuppressive Agents; Middle Aged; Simplexvirus; Treatment Outcome

HSV infection of adult humans occasionally results in life-threatening herpes simplex encephalitis (HSE) for reasons that remain to be defined. An animal system that could prove useful to model HSE could be microRNA-155 knockout (miR-155KO) mice. Thus, we observe that mice with a deficiency of miR-155 are highly susceptible to HSE with a majority of animals (75-80%) experiencing development of HSE after ocular infection with HSV-1. The lesions appeared to primarily represent the destructive consequences of viral replication, and animals could be protected from HSE by acyclovir treatment provided 4 d after ocular infection. The miR-155KO animals were also more susceptible to development of zosteriform lesions, a reflection of viral replication and dissemination within the nervous system. One explanation for the heightened susceptibility to HSE and zosteriform lesions could be because miR-155KO animals develop diminished CD8 T cell responses when the numbers, functionality, and homing capacity of effector CD8 T cell responses were compared. Indeed, adoptive transfer of HSV-immune CD8 T cells to infected miR-155KO mice at 24 h postinfection provided protection from HSE. Deficiencies in CD8 T cell numbers and function also explained the observation that miR-155KO animals were less able than control animals to maintain HSV latency. To our knowledge, our observations may be the first to link miR-155 expression with increased susceptibility of the nervous system to virus infection.

Topics: Acyclovir; Adoptive Transfer; Animals; Antiviral Agents; Brain; CD8-Positive T-Lymphocytes; Encephalitis, Herpes Simplex; Female; Flow Cytometry; Genetic Predisposition to Disease; Herpesvirus 1, Human; Host-Pathogen Interactions; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; MicroRNAs; Survival Analysis; Virus Replication

A 60-year-old woman suffered from high fever (38°C) and abnormal behavior, was admitted to our hospital on the seventh day of the fever. At admission, she was stuporous, and a cerebrospinal fluid (CSF) analysis revealed pleocytosis (55/μl, monocytes). Fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images showed high-intensity signals in the medial temporal lobe, inferior surface of the frontal cortex, right cerebellar vermis, and left thalamus. We diagnosed herpes simplex encephalitis, based on the finding of an elevated titer of herpes simplex virus antibody in the CSF (2.90). She was started on treatment with acyclovir and steroid pulse therapy, which was followed by rapid clinical improvement. After recovering from the stupor, the patient exhibited the symptoms of hypersomnia with low orexin level in the CSF. Thus, we should bear in mind that other than consciousness disturbance, patients with herpes simplex encephalitis can also present with rare complications due to the extent of the lesions.

Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; Biomarkers; Disorders of Excessive Somnolence; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Humans; Immunoglobulin M; Intracellular Signaling Peptides and Proteins; Magnetic Resonance Imaging; Male; Methylprednisolone; Middle Aged; Neuropeptides; Orexins; Pulse Therapy, Drug; Simplexvirus; Treatment Outcome

Herpes simplex virus (HSV) is one of the most common causes of sporadic encephalitis worldwide.. We aimed to determine clinical characteristics and prognosis of HSV encephalitis (HSVE) cases reviewed retrospectively from several collaborating centers.. We searched hospital archives of the last 10 years for patients with HSVE diagnosis, i.e. clinical presentation compatible with encephalitis and brain involvement on magnetic resonance imaging (MRI) and/or detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction (PCR). Clinical characteristics were noted and patients were phone-interviewed. HSVE cases were grouped and analyzed as proven and probable, based on virological confirmation by PCR. Univariate and multivariate analyses were used to determine factors associated with prognosis.. A total of 106 patients (63 males and 43 females; mean age, 44 years; range, 18-83 years) were included. Most common symptoms were changes in mental status, fever, headache, and seizure. HSV PCR was positive in 69% of patients tested, while brain involvement was detected on MRI in 95%. Acyclovir was started mostly within five days of main symptom and continued for ≥14 days. Case fatality rate was 8%, while 69% of patients recovered with sequelae. Favorable prognosis was observed in 73% of patients. Multivariate analysis identified the duration of disease before hospital admission (odds ratio (OR)=1.24) and the extent of brain involvement on MRI at the time of admission (OR=37.22) as two independent risk factors associated with poor prognosis.. Although HSVE fatality regressed considerably with acyclovir treatment, many patients survive with sequelae. Our results emphasize the importance of early diagnosis and prompt treatment of HSVE.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Brain; Cerebrospinal Fluid; DNA, Viral; Encephalitis, Herpes Simplex; Female; Humans; Interviews as Topic; Magnetic Resonance Imaging; Male; Middle Aged; Polymerase Chain Reaction; Radiography; Retrospective Studies; Simplexvirus; Treatment Outcome; Young Adult

Topics: Acyclovir; Antiviral Agents; Electroencephalography; Encephalitis, Herpes Simplex; Female; Humans; Infant; Magnetic Resonance Imaging; Meningitis, Bacterial; Neuroimaging; Practice Guidelines as Topic; Seizures, Febrile; Spinal Puncture

Topics: Acyclovir; Antiviral Agents; Aphasia; Cerebrospinal Fluid; Colonic Neoplasms; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Fever; Humans; Magnetic Resonance Imaging; Middle Aged; Polymerase Chain Reaction; Simplexvirus; Spinal Puncture; Temporal Lobe

Diagnostic strategies based on empirical testing and treatment to identify herpes simplex virus (HSV) infection in neonates may not be appropriate for older children in whom the most common presentation of severe infection is encephalitis, a rare and clinically recognizable condition.. Use of acyclovir in infants and children in 6 common non-HSV infection-related diagnosis-related groups was characterized between 1999 and 2012 at 15 US pediatric hospitals by using the Pediatric Health Information System database. Characteristics of non-neonatal patients at 1 institution tested for HSV encephalitis over a 6.5-year period were then analyzed to identify factors associated with potentially unnecessary testing and treatment.. Acyclovir use increased from 7.6% to 15.6% (P < .001) from 1999 to 2012. Much of this increase came in infants 30 to 60 days of age (82.7% increase, P < .001) and in patients with milder disease severity (44.8% increase, P < .001). Length of stay was increased by 2 days for children treated with acyclovir (P < .001). At our institution, 1394 HSV cerebrospinal fluid polymerase chain reactions were performed in children >30 days old, with only 3 positive results (0.22%). Comparison of the 3 subjects with positive testing and 55 with negative testing revealed that all cases, but only 4% (95% confidence interval 1.2%-14.0%) of noncases had clinical characteristics typical of HSV encephalitis.. Strategies for diagnosis and empirical treatment of suspected HSV encephalitis beyond the neonatal period have trended toward the approach common for neonates without evidence of an increase in disease incidence. This may result in increased medical costs and risk to patients.

Topics: Acyclovir; Antiviral Agents; Databases, Factual; Empirical Research; Encephalitis, Herpes Simplex; Female; Humans; Infant; Infant, Newborn; Male; Polymerase Chain Reaction; Simplexvirus

Topics: Acyclovir; Anticonvulsants; Antiviral Agents; Brain; Diagnosis, Differential; Electroencephalography; Encephalitis, Herpes Simplex; Female; Functional Laterality; Herpesvirus 1, Human; Humans; Infant; Magnetic Resonance Imaging; Phenobarbital

We experienced a right-handed 53-year-old man who presented with disturbance of consciousness and fever. Herpes simplex encephalitis (HSE) was diagnosed based on the detection of herpes simplex virus DNA in the cerebrospinal fluid. The administration of acyclovir for 42 days improved his consciousness level. Drowsiness, fever and seizures reappeared 20 days after stopping acyclovir treatment (day 67) and he responded well to vidarabine and methylprednisolone pulse therapy. An assessment of aphasia on day 98 revealed transcortical sensory aphasia. Brain MRI showed lesion in the left temporal lobe, bilateral insular cortexes and bilateral frontal lobe. His higher brain dysfunction continued. On day 156, he underwent hip replacement arthroplasty under general anesthesia sevoflurane. His higher brain dysfunction rapidly improved thereafter. We concluded that the accelerated improvement in our patient's higher brain function was related to the protective effect of sevoflurane. Some reports also show the protective effects of sevoflurane in experimental allergic encephalomyelitis by inhibition of T cell activation. These protective and anti-inflammatory effects may explain the accelerated improvement in higher brain function after general anesthesia.

Topics: Acyclovir; Anesthesia, General; Antiviral Agents; Arthroplasty, Replacement, Hip; Biomarkers; Brain; DNA, Viral; Encephalitis, Herpes Simplex; Humans; Magnetic Resonance Imaging; Male; Methyl Ethers; Methylprednisolone; Middle Aged; Neuroprotective Agents; Pulse Therapy, Drug; Sevoflurane; Simplexvirus; Treatment Outcome; Vidarabine

Topics: Acyclovir; Adolescent; Adult; Brain; Encephalitis, Herpes Simplex; Female; Humans; Infant, Newborn; Magnetic Resonance Imaging; Middle Aged; Spinal Puncture; Young Adult

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Microvascular Decompression Surgery; Trigeminal Neuralgia

Herpes simplex virus (HSV) encephalitis is a rare but often fatal disease if left untreated. A 50-year-old woman was admitted with lethargy, confusion, dysphasia and cough. MRI brain demonstrated bilateral temporal and perisylvian hyperintense signal abnormality extending into the cingulate gyrus, typical of HSV encephalitis. However, there was also signal abnormality involving the right thalamus, indicating thalamic involvement. EEG and cerebrospinal fluid PCR confirmed HSV encephalitis. The patient was started on intravenous acyclovir resulting in marked improvement. Adequate assessment and prompt treatment of HSV encephalitis will aid in achieving adequate recovery. Radiological investigation plays a crucial role in diagnosis with typical MR features a useful aid to diagnosis. HSV encephalitis classically involves the medial temporal lobes, insula and cingulated gyri. The basal ganglia and thalami are nearly always spared. We present a very rare case of HSV encephalitis which involved the right thalamus.

Topics: Acyclovir; Antiviral Agents; Dexamethasone; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Thalamus; Treatment Outcome

Acyclovir-induced neuropsychiatric symptoms (AINSs) may resemble several diseases of the central nervous system. Laboratory testing of acyclovir may be critical in supporting the diagnosis of AINSs when there is doubt. We present a case of suspected herpes encephalitis in which the diagnosis of AINSs was supported by therapeutic drug monitoring of plasma and cerebrospinal fluid concentrations of acyclovir and its main metabolite 9-carboxymethoxymethylguanine.

Topics: Acyclovir; Antiviral Agents; Central Nervous System; Diagnosis, Differential; Drug Monitoring; Encephalitis, Herpes Simplex; Female; Humans; Mental Disorders; Middle Aged; Neurotoxicity Syndromes

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Microvascular Decompression Surgery; Trigeminal Neuralgia

To describe two patients who developed an intracranial hematoma as a complication of temporal lobe encephalitis due to herpes simplex type 1 virus, and to review the literature.. The first patient, a 45-year-old woman developed a brain hematoma in the location of the encephalitic lesion on day 9 after the onset of herpes simplex encephalitis (HSE) that required surgical evacuation. The second patient, a 53-year-old woman was being treated for HSE; on day 8 after admission a temporal lobe hematoma with midline shift was disclosed due to persistent headache. Both patients survived but were left with sequelae. We conducted a PubMed/MEDLINE search from 1986 to April 2013 on this topic.. We have found 20 additional cases reported in the literature and review their characteristics. Hemorrhage was present on admission in 35% of pooled patients, and consistently involved the area of encephalitis. Clinical presentation of intracranial hemorrhage overlapped the encephalitic symptoms in two-thirds of the patients. Half of patients underwent surgery. Overall, mortality rate was low (5.2%), and half of patients fully recovered.. Intracranial bleeding, although infrequent, can complicate the evolution of herpes simplex encephalitis and should be borne in mind since its presence may require neurosurgery. Although its presentation may overlap the encephalitic features, the lack of improvement or the worsening of initial symptoms, particularly during the second week of admission, should lead to this suspicion and to perform a neuroimaging study.

Topics: Acyclovir; Antiviral Agents; Brain; Cerebral Hemorrhage; Decompressive Craniectomy; Encephalitis, Herpes Simplex; Female; Glasgow Coma Scale; Hematoma; Hepatitis C; Humans; Magnetic Resonance Imaging; Middle Aged; Nervous System Diseases; Neurosurgical Procedures; Tomography, X-Ray Computed; Treatment Outcome

Topics: Acute Disease; Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Glucocorticoids; Humans; Magnetic Resonance Imaging; Male; Methylprednisolone; Middle Aged; Pulse Therapy, Drug; Tomography, X-Ray Computed; Treatment Outcome

New onset refractory status epilepticus (NORSE) is a relatively novel concept used to describe a cohort of previously healthy young adults mostly women presenting with denovo refractory status epilepticus which has a miserable impact on the outcome. Various infectious and non-infectious causes have been considered to be responsible for this dreaded syndrome; however, many a times the exact cause is not identified. As therapy with antiepileptic and anaesthetic drugs is not so successful, identifying and treating the exact cause could improve the outcome. Here the authors describe a woman who presented with NORSE. Investigations confirmed the diagnosis of herpes simplex encephalitis (HSE) and she responded drastically to acyclovir along with complete control of seizures. In this case, NORSE was the presenting feature of HSE and the refractoriness of her seizures was terminated only after treating the exact cause, that is, encephalitis.

Topics: Acyclovir; Adult; Antiviral Agents; Electroencephalography; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Status Epilepticus

Acyclovir (ACV)-resistant (ACV(r)) mutants were generated from plaque-purified ACV-sensitive herpes simplex virus type 1 (HSV-1) by culturing the virus in Vero cells in the presence of 2-amino-7-(1,3-dihydroxy-2-propoxymethyl) purine (S2242). Three DNA polymerase (DNApol)-associated ACV(r) HSV-1 generated under ACV selection in a previous study (Suzutani, T., Ishioka, K., De Clercq, E., et al., Antimicrob. Agents Chemother., 47, 1707-1713, 2003) were also included. The sensitivity of the mutants to other antivirals and their neurovirulence were determined. The treatment efficacy of ACV and ganciclovir (GCV) against ACV(r) HSV-1 infections was evaluated in mice. Amino acid substitutions were demonstrated in conserved regions II and III in DNApol in 5 of the 6 mutants, while the other substitution was located in non-conserved regions. DNApol-associated ACV(r) clones showed cross-resistance to foscarnet, penciclovir, and vidarabine but were sensitive or hypersensitive to GCV, brivudin, sorivudine, and spongothymidine. The ACV(r) clone with an N815S mutation in DNApol showed similar neurovirulence to that of the parent virus; however, those with other mutations showed attenuation. GCV was effective in the treatment of the ACV(r) clone with similar virulence to that of parent HSV-1, while ACV was less effective in mice. These results indicate the importance of the characterization of HSV-1 isolates for the proper treatment of HSV-1 infections exhibiting ACV-resistance.

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Disease Models, Animal; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Mice; Mice, Inbred BALB C; Mutation; Selection, Genetic; Serial Passage; Treatment Outcome; Vero Cells; Viral Plaque Assay; Virulence

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease that essentially affects the white matter of the central nervous system. The diagnosis is based on clinical-imaging and developmental findings. Magnetic resonance imaging of the brain is the most useful diagnostic tool. The disease course is usually monophasic and the preferred initial treatment is with corticoids.. We conducted a retrospective study of 18 patients with a presumptive diagnosis of ADEM. Symptoms, imaging findings, progress and treatment were analysed. The definitive diagnosis was established in 12 patients, excluding one patient with positive polymerase chain reaction for herpes simplex virus in cerebrospinal fluid, one with a clinical picture that was consistent but normal magnetic resonance imaging of the brain, and four with an onset that was similar to ADEM whose definitive diagnoses were: Rassmusen's syndrome, haemophagocytic syndrome, brain tumour, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes).. The median age was 31 months with no predominance of either sex. Infection of the upper respiratory tract was the most frequent cause in children over 2 years of age and of the gastrointestinal tract in those under the age of 2. All of them presented altered levels of consciousness and multifocal neurological deficits. The most frequent imaging finding was multifocal alteration of the white matter in both hemispheres. Corticoids were the preferred treatment in most cases. Progression was favourable in nearly all patients except for two, who were left with important sequelae.. ADEM may present at any age, including in infants. There are a number of conditions that can mimic ADEM in the early stages.. Analisis de una serie de casos con diagnostico inicial de encefalomielitis aguda diseminada en el periodo 2000-2010.. Introduccion. La encefalomielitis aguda diseminada (EMAD) es una enfermedad desmielinizante que afecta fundamentalmente a la sustancia blanca del sistema nervioso central. El diagnostico se basa en hallazgos clinicorradiologicos y evolutivos. La resonancia magnetica cerebral es la herramienta diagnostica mas util. El curso suele ser monofasico y el tratamiento inicial de eleccion, los corticoides. Pacientes y metodos. Estudio retrospectivo de 18 pacientes con diagnostico de sospecha inicial de EMAD. Se analizo la sintomatologia, los hallazgos radiologicos, la evolucion y el tratamiento. El diagnostico definitivo se establecio en 12 pacientes, excluyendo un paciente con reaccion en cadena de la polimerasa positiva para el virus herpes simple en el liquido cefalorraquideo, uno con clinica compatible pero resonancia magnetica cerebral normal, y cuatro con inicio similar a EMAD cuyos diagnosticos definitivos fueron: sindrome de Rassmusen, sindrome hemofagocitico, tumor cerebral y MELAS (encefalomiopatia mitocondrial con acidosis lactica y accidentes cerebrovasculares). Resultados. La mediana de edad fue de 31 meses, sin predominio de sexo. La infeccion de la via respiratoria superior fue la causa mas frecuente en niños mayores y la gastrointestinal, en menores de 2 años. Todos presentaron alteracion en el nivel de conciencia y deficits neurologicos multifocales. El hallazgo radiologico mas frecuente fue la alteracion multifocal bihemisferica de la sustancia blanca. Los corticoides fueron el tratamiento de eleccion en la mayoria. La evolucion fue favorable en casi todos los pacientes excepto en dos, que tuvieron secuelas importantes. Conclusiones. La EMAD puede presentarse a cualquier edad, incluyendo lactantes. Hay multiples entidades que pueden simular una EMAD en un inicio.

Topics: Acyclovir; Adolescent; Adrenal Cortex Hormones; Antiviral Agents; Child; Child, Preschool; Diagnosis, Differential; Disease Progression; Encephalitis, Herpes Simplex; Encephalitis, Viral; Encephalomyelitis, Acute Disseminated; Female; Humans; Immunoglobulins, Intravenous; Infant; Lymphohistiocytosis, Hemophagocytic; Magnetic Resonance Imaging; Male; Plasmapheresis; Recovery of Function; Respiratory Tract Infections; Retrospective Studies; Spain; Symptom Assessment

A 28 years old female presented with headache, fever, altered sensorium and right side weakness for one week. She was febrile and drowsy with right sided hemiplegia and papilledema. Tuberculous or bacterial meningitis, tuberculoma and abscess were at the top of the diagnosis list followed by Herpes simplex meningo-encephalitis (HSE). MRI showed abnormal signal intensity of left temporal lobe without significant post-contrast enhancement and midline shift. CSF examination was normal, gram stain and Ziehl-Neelsen stain showed no micro-organism, or acid fast bacilli. CSF for MTB PCR was negative. PCR DNA for Herpes simplex 1 on CSF was detected. Acyclovir was started and the patient was discharged after full recovery. A high index of suspicion is required for HSE diagnosis in Pakistan where other infections predominantly affect the brain and HSE may be overlooked as a potential diagnosis.

Topics: Acyclovir; Adult; Antiviral Agents; Cerebrospinal Fluid; DNA, Viral; Encephalitis, Herpes Simplex; Female; Fever; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Paresis; Polymerase Chain Reaction; Treatment Outcome

The added benefit of combining valacyclovir (VACV), an antiviral agent, with etanercept (ETA), an anti-tumor necrosis factor alpha (TNF-α) antibody, for the treatment of herpes simplex virus type 1 (HSV-1) encephalitis (HSE) was evaluated in a mouse model. BALB/c mice were infected intranasally with 1.85 × 104 plaque forming units of HSV-1. Groups of mice received a single intraperitoneal injection of vehicle or ETA (400 μg/mouse) on day 3 post-infection combined or not with VACV (1 mg/ml of drinking water) from days 3 to 21 post-infection. On day 5 post-infection, groups of mice were sacrificed for determination of viral DNA load, detection of ETA in brain homogenates and for in situ hybridization. The survival rate of mice was significantly increased when VACV was administered in combination with ETA (38.5% for VACV vs 78.6% for combined treatment; P = 0.04) although VACV or ETA alone had no significant effect compared to the vehicle. The benefit of combined therapy was still present when treatment was delayed until day 4 post-infection. The viral DNA load was significantly reduced in mice treated with VACV alone (P < 0.01) or combined with ETA (P < 0.05) compared to the uninfected group whereas ETA alone had no effect. These results reinforce the notion that both virus-induced and immune-related mechanisms participate in the pathogenesis of HSE and suggest that potent antiviral agent could be combined with immune-based therapy, such as a TNF-α inhibitor, to improve prognosis of HSE.

Topics: Acyclovir; Animals; Antiviral Agents; Brain; DNA, Viral; Drug Administration Schedule; Drug Evaluation, Preclinical; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Etanercept; Herpesvirus 1, Human; Immunoglobulin G; Immunotherapy; Mice; Mice, Inbred BALB C; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha; Valacyclovir; Valine

Topics: Acyclovir; Adult; Brain Edema; Cerebral Hemorrhage; Craniotomy; Emergencies; Encephalitis, Herpes Simplex; Fatal Outcome; Female; Hematoma; Hemiplegia; Humans; Magnetic Resonance Imaging; Mydriasis; Respiratory Insufficiency; Temporal Lobe; Tomography, X-Ray Computed

A neonate with herpes simplex virus 1 encephalitis was treated with intravenous acyclovir. During the course of therapy, the infection became intractable to the treatment and a mutation in the viral thymidine kinase gene (nucleotide G375T, amino acid Q125H) developed. This mutation was demonstrated in vitro to confer acyclovir resistance.

Topics: Acyclovir; Amino Acid Substitution; Antiviral Agents; DNA, Viral; Drug Resistance, Viral; Encephalitis, Herpes Simplex; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Male; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation, Missense; Pregnancy Complications, Infectious; Sequence Analysis, DNA; Thymidine Kinase

The authors present the first reported case of herpes simplex encephalitis (HSE) precipitated by trigeminal nerve microvascular decompression (MVD). The presentation of this specific case together with the pathogenesis and management of HSE are discussed, with a relevant literature review. This 29-year-old woman with treatment-resistant trigeminal neuralgia underwent a successful elective MVD of the right trigeminal nerve. She was discharged but was readmitted 1 week postoperatively with clinical signs and symptoms of meningitis. A CSF sample was obtained through lumbar puncture before she was treated initially with ceftriaxone. The polymerase chain reaction test of CSF was later positive for herpes simplex virus Type 1, at which point the patient was switched to a 2-week course of intravenous acyclovir before being discharged. Although this disease is rare, to avoid a delay in antiviral treatment the authors suggest that HSE should be considered in any patient presenting with a meningoencephalitic picture following MVD.

Topics: Acyclovir; Adult; Antiviral Agents; Cerebrospinal Fluid; Electroencephalography; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Infusions, Intravenous; Magnetic Resonance Imaging; Microvascular Decompression Surgery; Spinal Puncture; Trigeminal Neuralgia

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.

Topics: Acyclovir; Adolescent; Aged; Aged, 80 and over; Antiviral Agents; DNA, Viral; Encephalitis, Herpes Simplex; Encephalitis, Varicella Zoster; Female; France; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; Humans; Infant, Newborn; Magnetic Resonance Imaging; Male; Middle Aged; Polymerase Chain Reaction; Prospective Studies; Tomography, X-Ray Computed; Treatment Outcome

In this case report we describe the first non-fatal herpes simplex virus encephalitis (HSE) case with natalizumab for multiple sclerosis (MS). A 36-year-old woman, previously treated with immunomodulatory and immunosuppressive drugs for MS, developed acute encephalitis after 6 monthly natalizumab perfusions. Brain imaging demonstrated suggestive bi-temporal lesions. Herpes simplex virus type-1 DNA was detected in cerebrospinal fluid. The patient improved gradually after a 21-day course of intravenous acyclovir, but neuropsychiatric changes remained 5 months later. Our non-fatal case of HSE and other reported cases of herpes infections provide evidence of an increased risk with natalizumab and point to the need for clinicians to maintain awareness.

Topics: Acyclovir; Adult; Antibodies, Monoclonal, Humanized; Antiviral Agents; Cognition; DNA, Viral; Drug Administration Schedule; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Immunologic Factors; Infusions, Intravenous; Magnetic Resonance Imaging; Memory; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Time Factors; Treatment Outcome; Virus Activation

To describe herpes simplex virus encephalitis despite normal cell count in the cerebrospinal fluid in patients with malignoma after whole brain irradiation.. Blood and cerebrospinal fluid analysis and magnetic resonance imaging.. Three male and two female patients with malignoma and a recent history of whole-brain irradiation presented with impaired consciousness with or without epileptic seizure. Although cerebrospinal fluid analysis revealed a normal cell count, herpes simplex virus DNA was detected in all samples by polymerase chain reaction.. In patients with impaired consciousness, epileptic seizure, or temporal lobe symptoms of new onset and a recent history of brain irradiation with normal cerebrospinal fluid, an atypical anergic course of herpes simplex virus encephalitis should be considered. Herpes simplex virus polymerase chain reaction should be used as method of choice to detect herpes simplex virus genomes as early as possible rather than relying on routine cerebrospinal fluid parameters. Importantly, antiviral therapy should be started without delay in any case of faint suspicion and should be continued until herpes simplex virus encephalitis is clearly ruled out.

Topics: Acyclovir; Aged; Antiviral Agents; Brain Neoplasms; Encephalitis, Herpes Simplex; Fatal Outcome; Female; Herpesvirus 1, Human; Humans; Immunocompromised Host; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging

The introduction of polymerase chain reaction (PCR) for the diagnosis of herpesvirus central nervous system infections is reshaping our understanding of these illnesses. Varicella-zoster virus (VZV) is increasingly recognized as an important etiology of sporadic viral meningoencephalitis (ME). Furthermore, mild cases of herpes simplex virus (HSV) ME, traditionally considered a devastating infection, are frequently reported.. We compared the demographic and clinical features of patients with VZV (20) and HSV (17) ME diagnosed by Real-Time PCR of cerebrospinal samples in a single center during the years 2002-2010.. VZV and HSV patients were comparable with respect to age, sex, underlying diseases, immune suppression, and the rates of fever, headache and altered mental status on presentation. Seizures, focal neurological signs, systemic complications and in-hospital death were noted only in the HSV group.. Our study confirms the prevalence of VZV as a cause of sporadic ME over the last decade. While patients with HSV ME had more manifestations of severe disease, there also was a significant overlap with clinical and laboratory parameters of VZV ME. In the absence of dermatomal rash, differentiation between VZV and HSV ME on clinical grounds alone may represent a true challenge.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Brain; Child; Child, Preschool; DNA, Viral; Electroencephalography; Encephalitis, Herpes Simplex; Encephalitis, Varicella Zoster; Female; Hospital Mortality; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Real-Time Polymerase Chain Reaction; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

We present a patient with polymorphic ventricular tachycardia and subsequent ventricular fibrillation with acquired long QT syndrome secondary to herpes encephalitis.

Topics: Acute Disease; Acyclovir; Antiviral Agents; Defibrillators, Implantable; Electrocardiography; Encephalitis, Herpes Simplex; Female; Foscarnet; Ganciclovir; Headache; Heart Arrest; Herpesvirus 2, Human; Humans; Long QT Syndrome; Magnetic Resonance Imaging; Meningitis, Viral; Middle Aged; Seizures; Tachycardia, Ventricular; Torsades de Pointes

A previously healthy 31-year-old G4P2 woman at 33 weeks of gestation was admitted as an emergency with a pyrexia of 39°C, vomiting, headache and neck stiffness associated with photophobia, phonophobia and visual and auditory symptoms. There were no heraldic signs of eclampsia. Polymerase chain reaction and testing for herpes simplex virus in the cerebrospinal fluid diagnosed herpes simplex-1 meningoencephalitis. Following acyclovir, the clinical course improved. Spontaneous vaginal delivery occurred at 39 weeks of gestation with epidural analgesia using ropivacaine. Mother and child were neurologically normal and healthy 15 months later. Early administration of acyclovir is essential to reduce the risk of neurological complications. After treatment and a negative polymerase chain reaction for herpes simplex virus in the cerebrospinal fluid, epidural analgesia with local anesthetic and sufentanil is possible.

Topics: Acyclovir; Adult; Antiviral Agents; Brain; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Follow-Up Studies; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Third; Virus Activation

Topics: Acyclovir; Antiviral Agents; Child; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male

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.. 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.. 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%).. 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.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Diagnosis, Differential; DNA, Viral; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies; Time Factors; Young Adult

The number of case reports on elderly-onset herpes simplex encephalitis (HSE) has been increasing. We encountered the case of an 89-year-old woman with HSE, who was probably one of the oldest-onset patients in Japan. She was a bed patient with underlying diseases of old cerebral infarction and cholangitis. These conditions might be risk factors for the onset of HSE. Concerning HSE among the elderly, it is important to pay attention to underlying diseases that weaken their immunity. Although we delayed in diagnosing her case and started treatment 1 month after convulsions appeared, she completely recovered with intravenous acyclovir (ACV) therapy. However, relapse occurred 2 months after the therapy ended. We treated her again with intravenous ACV but she died without improvement. ACV, which was initially effective, was ineffective at relapse. Cases of ACV-resistant herpes simplex virus (HSV) infection have been reported in immunodeficient patients. The immune system of elderly patients is sometimes too weak to suppress the mutation of the virus. In this case, the HSV may have become resistant to ACV. Therefore, the possibility of ACV resistance should be considerd in HSE relapse in the elderly population.

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Encephalitis, Herpes Simplex; Fatal Outcome; Female; Humans; Secondary Prevention; Simplexvirus

We aimed to audit the regional management of central nervous system (CNS) infection in children.. The study was undertaken in five district general hospitals and one tertiary paediatric hospital in the Mersey region of the UK. Children admitted to hospital with a suspected CNS infection over a three month period were identified. Children were aged between 4 weeks and 16 years old. Details were recorded from the case notes and electronic records. We measured the appropriateness of management pathways as outlined by national and local guidelines.. Sixty-five children were identified with a median age of 6 months (range 1 month to 15 years). Ten had a CNS infection: 4 aseptic meningitis, 3 purulent meningitis, 3 encephalitis [2 with herpes simplex virus (HSV) type 1]. A lumbar puncture (LP) was attempted in 50 (77%) cases but only 43 had cerebrospinal fluid (CSF) available for analysis. Of these 24 (57%) had a complete standard set of tests performed. Fifty eight (89%) received a third generation cephalosporin. Seventeen (26%) also received aciclovir with no obvious indication in 9 (53%). Only 11 (65%) of those receiving aciclovir had CSF herpes virus PCR. Seventeen had cranial imaging and it was the first management step in 14. Treatment lengths of both antibiotics and aciclovir were highly variable: one child with HSV encephalitis was only treated with aciclovir for 7 days.. The clinical management of children with suspected CNS infections across the Mersey region is heterogeneous and often sub-optimal, particularly for the investigation and treatment of viral encephalitis. National guidelines for the management of viral encephalitis are needed.

Topics: Acyclovir; Adolescent; Anti-Bacterial Agents; Antiviral Agents; Cephalosporins; Child; Child, Preschool; Cohort Studies; Cross-Sectional Studies; Encephalitis; Encephalitis, Herpes Simplex; England; Female; Guideline Adherence; Herpesvirus 1, Human; Humans; Infant; Male; Medical Audit; Meningitis; Odds Ratio; Practice Guidelines as Topic; Retrospective Studies; Spinal Puncture

Herpes simplex encephalitis is a diagnostic challenge and causes high morbidity and mortality in children. Early suspicion of the disease and a rapid, safe and useful diagnostic test are relevant because up to 70% of the cases may die. We report the case of a newborn girl aged 25 days, who presented with a clinical picture that was compatible with herpes simplex encephalitis where the confirmation of the etiological diagnosis was delayed. Only by repeated real-time polymerase chain reaction it was possible to confirm the presence of herpes simplex virus type 1 in the cerebrospinal fluid.

Topics: Acyclovir; Antiviral Agents; Delayed Diagnosis; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Real-Time Polymerase Chain Reaction

To characterize clinical features, neuroimaging, and outcomes of herpes simplex encephalitis (HSE) in immunocompromised individuals.. We performed a retrospective case control review of patients diagnosed with HSE. Adult patients were dichotomized into immunocompromised (n = 14) and immunocompetent groups (n = 15).. Fewer immunocompromised patients presented with prodromal symptoms and focal deficits. While the majority of CSF profiles in the immunocompromised patients were mononuclear cells predominant, 3 had polymorphonuclear predominance and another 3 had normal profiles. MRI showed widespread cortical involvement, with brainstem or cerebellar involvement in some. Two immunocompromised patients had recurrent HSE. The immunosuppressed state was associated with a decrease in Karnofsky Performance Status Scale (KPSS) score of 23.1 (p = 0.018). Every 1-day delay in initiation of acyclovir was associated with a decrease in KPSS of 10.2 (p = 0.002), and every 10 cell/mm(3) increase of CSF leukocytosis was associated with an increase in KPSS of 0.7 (p = 0.009). Mortality rate was 6 times higher in the immunocompromised patients.. Immunocompromised states may predispose to HSE with atypical clinical and neuroradiologic features. Immunocompromised individuals with HSE have significantly worse outcomes and mortality. Early diagnosis and treatment is associated with improved outcome. The findings are particularly important in light of the increasing use of potent immunosuppressive and immunomodulatory therapies.

Topics: Acyclovir; Adult; Aged; Case-Control Studies; Cohort Studies; Encephalitis, Herpes Simplex; Female; Humans; Immunocompromised Host; Male; Middle Aged; Prodromal Symptoms; Retrospective Studies; Treatment Outcome

Despite antiviral treatment and advances in critical care, the Herpes simplex encephalitis (HSE) still has a poor outcome in a significant portion of patients. In severe cases of HSE, reduced carbon dioxide reactivity is usually present and these patients don't respond to the usual treatment of brain edema and intracranial hypertension. We present case series of patients with severe form of HSE treated with therapeutic hypothermia (TH) and describe in detail the indications, methods, and the rationale for its use. In this case series, patients presented with severely impaired consciousness and very high predicted death rate as measured by Glasgow coma scale and Acute Physiology and Chronic Health Evaluation (APACHE II) score respectively. According to our findings, TH in carefully selected patients with HSE holds promise as an adjunctive to the antiviral treatment.

Topics: Acyclovir; Aged; Antiviral Agents; Brain Edema; Carbon Dioxide; Disease Progression; Encephalitis, Herpes Simplex; Encephalocele; Glasgow Coma Scale; Humans; Hypothermia, Induced; Infusions, Intravenous; Male; Middle Aged; Optic Nerve; Oximetry; Prognosis; Tomography, X-Ray Computed; Ultrasonography, Doppler, Transcranial

Topics: Acyclovir; Adult; Antiviral Agents; Brain; Encephalitis, Herpes Simplex; Female; Humans; Male; Young Adult

Herpes simplex encephalitis is associated with substantial morbidity and mortality and may be related to timely diagnosis and treatment. While awaiting the results of testing, hospitalization and empiric treatment with acyclovir is recommended, though the direct and indirect costs associated with this management are substantial. We sought to examine children hospitalized for possible herpes simplex encephalitis, following clinical and laboratory assessment in the emergency department, and empiric treatment with acyclovir, in order to describe the proportion receiving a complete course of treatment; and to identify the clinical variables which are associated with receiving a complete course, as compared with an incomplete course of acyclovir.. Hospitalized children prescribed acyclovir were included in this case control study. Clinical, laboratory and diagnostic variables were abstracted for children prescribed a complete (≥ 14 days) or an incomplete course (<14 days) of acyclovir. Odds ratios and 95% confidence intervals were calculated.. 289 children met eligibility criteria, 30 (10%) received a complete course and 259 (90%) received an incomplete course. A history of mucocutaneous herpes simplex virus infection (p < 0.01), Glasgow Coma Scale ≤ 13 (p = 0.02), focal neurologic findings (p = 0.001) and elevated cerebrospinal fluid white blood cell count (p = 0.05) were associated with a complete course of acyclovir.. Many children did not complete a full course of therapy. Unnecessary testing and treatment is burdensome to families and the health care system. Possible predictive variables include abnormal Glascow Coma Scale, focal neurologic findings and cerebrospinal fluid pleocytosis.

Topics: Acyclovir; Antiviral Agents; Case-Control Studies; Chi-Square Distribution; Child; Child, Hospitalized; Encephalitis, Herpes Simplex; Female; Humans; Male; Patient Selection; Treatment Outcome

An example of diagnostics and treatment of patient is in-process made with herpetic encephalitis. It is well-proven in researches, that a herpetic encephalitis is 11.5% among sharp encephalitises. Morbidity is sporadic, some researchers specify on an increase its spring. An infection can be passed tiny and pin a way. Seasonal vibrations are not incident to the herpetic encephalitis. Two peaks of morbidity are on 5-30 years and age more senior 50 years. More than in 95% cases the virus of simple herpes of type serves as an exciter of herpetic encephalitis 1. A characteristic triad of herpetic encephalitis is the sharp feverish beginning, development of cramps of dzheksonovskogo type and violation of consciousness, developing usually after a brief respirator infection. Sometimes sudden development of cramps and loss of consciousness is preceded a fever. Example of such development of disease is made an in our work.

Topics: Acyclovir; Adult; Antiviral Agents; Echocardiography; Electroencephalography; Encephalitis, Herpes Simplex; Female; Herpesvirus 7, Human; Humans; Roseolovirus Infections; Treatment Outcome; Young Adult

Topics: Acyclovir; Adult; Dexamethasone; Encephalitis, Herpes Simplex; Female; Humans; Pregnancy; Pregnancy Complications, Infectious

Topics: Acyclovir; Adult; Antiviral Agents; Child; Child, Preschool; Encephalitis, Herpes Simplex; England; Humans; Infant, Newborn; Simplexvirus; Time Factors; Treatment Outcome

Relapsing herpes simplex encephalitis (HSE) rarely occurs after acyclovir treatment. We treated a patient with relapsing HSE of the contralateral temporal lobe, resulting in Klüver-Bucy syndrome, after a full-dose acyclovir treatment. This case suggests that physicians should consider sudden behavioral and emotional changes after HSE treatment as a possible indication of relapsing HSE, as well as possible temporal lobe epilepsy, and the need to administer longer acyclovir treatment for select patients.

Topics: Acyclovir; Adult; Antiviral Agents; Brain; Dose-Response Relationship, Drug; Electroencephalography; Encephalitis, Herpes Simplex; Humans; Kluver-Bucy Syndrome; Magnetic Resonance Imaging; Male; Recurrence; Treatment Outcome

A 62-year-old woman with an autoimmune disease presented with panuveitis and was treated with immune suppression. She subsequently developed herpetic acute retinal necrosis and later died of herpes simplex encephalitis. Acute retinal necrosis usually occurs months to years after herpes simplex encephalitis. In our case, the ocular findings were present for 5 weeks before the encephalitis presented. To our knowledge, this is the first Australian case of acute retinal necrosis preceding herpes simplex encephalitis.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Glucocorticoids; Herpes Simplex; Herpesvirus 1, Human; Humans; Middle Aged; Panuveitis; Prednisolone; Retinal Necrosis Syndrome, Acute

Herpesviruses can cause an acute, subacute, or chronic disease state in both immunocompetent and immunocompromised individuals. Herpes simplex virus (HSV) encephalitis is most often an acute monophasic disease process. Rarely, however, it may progress to a chronic state, and more rarely still to a granulomatous encephalitis. Prior studies have suggested that antiviral immunity with Toll-like receptors determines susceptibility to herpesviruses. The authors report the case of a 14-year-old girl with a remote history of treated HSV encephalitis, who had intractable seizures and worsening MR imaging changes that were concerning for either a neoplastic or an inflammatory process. She was found to have granulomatous herpes simplex encephalitis and had a low cytokine response to Toll-like receptor 3 stimulation.

Topics: Acyclovir; Adolescent; Antiviral Agents; Brain Neoplasms; Contrast Media; Cytokines; Demyelinating Autoimmune Diseases, CNS; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Granuloma; Humans; Magnetic Resonance Imaging; Seizures; Toll-Like Receptor 3; Treatment Outcome

We report the case of a young patient who had a past history of HSV encefalitis and presented for decreased vision in her left eye associated with pain and red eye.

Topics: Acyclovir; Administration, Oral; Adrenocortical Hyperfunction; Adult; Antiviral Agents; Body Mass Index; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Glucocorticoids; Humans; Injections, Intravenous; Obesity; Panuveitis; Risk Factors; Simplexvirus; Treatment Outcome

To investigate how infants and children with suspected viral encephalitis are currently managed in a UK tertiary children's hospital.. Case notes of all infants and children who received intravenous aciclovir for suspected encephalitis over a 6-month period were reviewed. Suspected viral encephalitis was defined as a child with fever or history of febrile illness and a reduced level of consciousness, irritability or a change in personality or behaviour or focal neurological signs.. Fifty one children were identified. Two had proven herpes simplex encephalitis (HSV) and two had clinically diagnosed viral encephalitis with no cause identified. Forty children had cerebrospinal fluid (CSF) analysis, but basic results were incomplete in 13 cases. CSF was sent for the detection of HSV DNA by PCR in 27 cases. The initial dose of aciclovir was incorrect in 38 cases. The median (range) length of intravenous aciclovir treatment was 4 (1-21) days. Six children were given a full course of aciclovir (10 or more days). For 14 children, there appeared to be no real indication for starting aciclovir. Case note documentation was generally inadequate.. The management of children with suspected viral encephalitis appears haphazard in many cases. Guidelines for the management of children with suspected viral encephalitis are needed.

Topics: Acyclovir; Adolescent; Antiviral Agents; Child; Child, Preschool; DNA, Viral; Drug Administration Schedule; Encephalitis, Herpes Simplex; Encephalitis, Viral; Female; Glasgow Coma Scale; Humans; Infant; Infant, Newborn; Injections, Intravenous; Male; Practice Guidelines as Topic; Retrospective Studies; Simplexvirus; Spinal Puncture; Treatment Outcome

Topics: Acyclovir; Adrenal Cortex Hormones; Anti-Dyskinesia Agents; Antiviral Agents; Brain; Child, Preschool; Clonazepam; Dyskinesias; Encephalitis, Herpes Simplex; Female; Haloperidol; Humans; Magnetic Resonance Imaging

Herpes simplex virus (HSV) hepatitis has a fatal impact on the outcome of organ transplanted recipients. Here, we present a thought-provoking case of HSV hepatitis in a high-risk recipient after living-related liver transplantation (LRLT). A 1-month-old female newborn infant was affected by HSV encephalitis. Fulminant hepatic failure (FHF) of unknown etiology occurred suddenly at 4.4 years of age. Viral infections were ruled out as the cause of FHF. Intensive care including plasma exchange (PE) was started, and the preoperative treatments for ABO incompatibility were performed. Thereafter, LRLT was performed emergently. Although strong immunosuppression for ABO incompatibility was continued after LRLT, antibody-mediated rejection (AMR) occurred on postoperative day (POD) 4. PE was repeated and improvements were obtained. However, liver dysfunction appeared on POD 8. Histopathological findings of liver needle biopsy clearly revealed HSV hepatitis, although the results of HSV DNA and antibody titer in blood sample did not clearly indicate HSV infection. On POD 21, thrombotic microangiopathy (TMA) occurred and the plasma and immunoglobulin were replenished. Our pediatric recipient recovered successfully from AMR, HSV hepatitis, TMA, and repeated sepsis. We conclude that well considered therapy based on the real-time detection of HSV hepatitis is indispensable for the further improvements of outcome in HSV hepatitis after LRLT.

Topics: Acyclovir; Antiviral Agents; Child, Preschool; Encephalitis, Herpes Simplex; Female; Hepatitis, Viral, Human; Humans; Liver Failure, Acute; Liver Transplantation; Simplexvirus

We report a case of a 35-year-old female with herpetic meningoencephalitis confirmed by polymerase chain reaction and immunohistochemical study for herpes simplex virus-1 accompanied with a massive intracerebral hematoma as a complication. A hematoma localized at the medial temporal lobe and the medial frontal lobe occurred on the 11th day after initiation of acyclovir treatment. She subsequently required emergency surgery for temporal lobectomy, as well as hematoma and external decompression. Intracerebral hematoma with MR imaging showed gyral pattern along the cortex of the medial temporal lobe and the base of the medial frontal lobe. We speculate that the hemorrhage occurred by rupture of small vessels affected by vasculitis in addition to hypertension caused by increased intracranial pressure. We therefore emphasize the risk of intracerebral hemorrhage at an early stage or during acyclovir treatment, especially during one or two weeks after initiation of the treatment, and the necessity of careful observation during these periods.

Topics: Acyclovir; Adult; Antiviral Agents; Cerebral Hemorrhage; Encephalitis, Herpes Simplex; Female; Frontal Lobe; Hematoma; Humans; Temporal Lobe

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Epilepsy, Tonic-Clonic; Humans; Male; Melanoma; Meningeal Neoplasms; Paraparesis; Quadriplegia; Ventriculostomy

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Headache; Herpesvirus 1, Human; Humans; Middle Aged; Photophobia

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.

Topics: Acyclovir; Adult; Antiviral Agents; Drug Resistance, Viral; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging

To test the hypothesis that predisposition to childhood herpes simplex virus (HSV) type 1 encephalitis (HSE) may be determined in part by human genetic factors.. A genetic epidemiologic survey of childhood HSE (onset at age 3 months to 15 years) over a 20-year period (1985-2004) was conducted throughout France (comprising 29 university hospital neuropediatric centers). A total of 85 children fulfilled the diagnostic criteria for inclusion. Family and personal histories were obtained by face-to-face interview for 51 patients.. No familial cases of HSE were identified in our survey; however, a high proportion (20%) of the children interviewed had a relevant family history: parental consanguinity (12% of patients), early-onset herpetic keratitis in a first-degree relative (6%), or both (2%). The narrow window of high susceptibility to HSE before age 3 years (62% of patients) further indicates that predisposition to HSE is tightly age-dependent.. This survey suggests that childhood HSE, although sporadic, may result from Mendelian predisposition (from autosomal recessive susceptibility in particular), at least in some children. There likely is incomplete penetrance, however, which may reflect, at least in part, the impact of age at the time of HSV-1 infection.

Topics: Acyclovir; Adolescent; Age Factors; Age of Onset; Antiviral Agents; Child; Child, Preschool; Encephalitis, Herpes Simplex; Female; Genetic Predisposition to Disease; Genetic Variation; Humans; Infant; Male; Risk Factors; Simplexvirus; Toll-Like Receptor 3; Young Adult

Infantile herpes simplex virus encephalitis (HSVE) infection remains a significant cause of morbidity and mortality. Diagnosis is often difficult in this population, where a specific pattern of clinical and laboratory signs are lacking. This often results in unnecessary treatment of infants with empiric acyclovir. This study evaluates the use of empiric acyclovir at the Kentucky Children's Hospital and attempts to correlate any laboratory or clinical findings that may be highly suggestive of HSVE.. Medical records of infants younger than 1 year admitted and treated with acyclovir were evaluated for any consistent pattern of clinical findings suggestive of HSVE. Specifically, serum and cerebrospinal fluid (CSF) white blood cell counts, red blood cell counts, cerebrospinal glucose and protein, and clinical neurological findings upon admission were evaluated.. Two hundred eighteen infants were identified and included in the study. Three infants were identified with polymerase chain reaction-positive HSVE. Only CSF leukocytosis was consistent among HSVE-positive infants. All infants with HSVE exhibited generalized neurological findings. Neither hemorrhagic CSF nor focal neurological findings were indicative of HSVE infection.. Herpes simplex virus encephalitis has a very low prevalence within this population. Clinically significant neurological findings as well as specific risk factors must be present to consider treatment with empiric acyclovir. Apnea and focal seizures are not specific risk factors for herpetic meningitis in infants. Lack of a CSF leukocytosis is a strong negative predictor for HSVE, and hemorrhagic fluid is not specific for HSVE.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Infant; Leukocytosis; Male; Retrospective Studies; Spinal Puncture

Human brains harbor herpes simplex virus type-1 (HSV-1) DNA, which normally remains quiescent throughout many decades of life. HSV-1 is associated with viral encephalopathy and with the amyloid beta 42 (Abeta42) peptide-enriched lesions that characterize Alzheimer's disease neuropathology. Here we report that infection of human neuronal-glial cells in primary co-culture with HSV-1 induces an irregular hypertrophy of human neuronal-glial cell bodies, an induction of HSV-1 DNA polymerase, and an up-regulation of micro-RNA-146a associated with altered innate-immune responses. Presence of the antiviral acyclovir or soluble Abeta42 peptide significantly attenuated these neuropathological responses. The inhibitory effects of Abeta42 peptide were also observed in an HSV-1-infected CV-1 cell-based viral plaque assay. The results suggest that soluble Abeta42 peptide can invoke non-pathological and anti-viral effects through inactivation of an HSV-1 challenge to human brain cells by simple viral sequestration, viral destruction, or by complex neurogenetic mechanisms.

Topics: Acyclovir; Amyloid beta-Peptides; Antiviral Agents; Cells, Cultured; Coculture Techniques; Down-Regulation; Encephalitis, Herpes Simplex; Gene Expression Regulation, Viral; Herpesvirus 1, Human; Humans; MicroRNAs; Neuroglia; Peptide Fragments; RNA, Viral; Up-Regulation

Granulocytic sarcomas, or chloromas, are extramedullary collections of immature granulocytes. Central nervous system involvement is rare and of those cases described, most are complications of acute myelogenous leukemia.. A 40-year-old man with chronic myelogenous leukemia presented with seizure and encephalopathy. Magnetic resonance imaging of the brain revealed temporal T2 hyperintensities with gyriform cortical enhancement. Cerebrospinal fluid showed mild pleocytosis and elevated protein. Electroencephalography demonstrated periodic lateralized epileptiform discharges. Acyclovir was initiated for herpes simplex encephalitis, however, follow-up MRI showed extension of the lesion. MR spectroscopy suggested tumor, confirmed by brain biopsy. Postradiation MRI showed a significant decrease in lesion size.. Granulocytic sarcoma can present as intraparenchymal cerebral lesions in patients with chronic myelogenous leukemia and may mimic herpes simplex encephalitis.

Topics: Acyclovir; Adult; Antiviral Agents; Biopsy; Brain; Brain Neoplasms; Diagnosis, Differential; Electroencephalography; Encephalitis, Herpes Simplex; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Magnetic Resonance Imaging; Male; Sarcoma, Myeloid

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Infant; Prognosis

Acute retinal necrosis, caused by the herpes family of viruses, is a rapidly progressing ocular inflammatory disorder commonly reported in adults but rarely in children. The accepted diagnostic criteria include presence of 1 or more foci of retinal necrosis, rapid progression, circumferential spread, occlusive vasculopathy, and inflammation in the vitreous and anterior chamber. We report bilateral acute retinal necrosis with encephalitis due to herpes simplex virus (HSV-2) in newborn twins.

Topics: Acute Disease; Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Herpes Genitalis; Herpesvirus 2, Human; Humans; Infant, Newborn; Infant, Premature; Infectious Disease Transmission, Vertical; Male; Necrosis; Retinitis; Twins

A pregnant 25-year-old woman at 32 weeks' gestation was admitted to an emergency unit after her husband had found her drowsy and with her tongue bitten. The day before admission, the patient had developed a fever of 39 degrees C, was suffering from headaches, was nauseated and had vomited. On admission, she had anterograde and retrograde amnesia, but no somatic neurological deficits were detected.. Routine laboratory testing, lumbar puncture, cerebrospinal fluid analysis, routine bacteriology, brain MRI, and polymerase chain reaction testing for neurotropic viruses including herpes simplex virus types 1 and 2.. Maternal herpes simplex virus type 1 encephalitis.. Antiviral and anticonvulsive therapy, supportive treatment, and cesarean section.

Topics: Acyclovir; Adult; Anticonvulsants; Antiviral Agents; Brain; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Lamotrigine; Magnetic Resonance Imaging; Pregnancy; Pregnancy Complications, Infectious; Seizures; Triazines

Herpes simplex virus encephalitis (HSVE) patients occasionally follow a prolonged course despite standard antiviral treatment. The purpose of this study was to analyze clinical variables to identify predictors of a prolonged course.. A series of 23 HSVE patients treated with acyclovir (ACV) during the acute stage were selected and divided into 2 groups: the non-prolonged group (n = 15), with improvement within 2 weeks after initial ACV treatment; and the prolonged group (n = 8), without improvement within 2 weeks. Differences in clinical variables, including age, duration from onset to initial ACV treatment, Glasgow coma scale (GCS) score, corticosteroid administration, detection of abnormal lesions on initial cranial computed tomography (CT) and magnetic resonance imaging, detection of periodic lateralized epileptiform discharges on electroencephalogram, and clinical outcome, were compared between the groups.. There were significant differences in GCS score, clinical outcome, and detection of lesions on CT between the non-prolonged and prolonged groups [p = 0.021, p = 0.041 (Mann-Whitney's U test), respectively, and p = 0.027 (Fisher's exact test)]. Four of the eight patients with a prolonged course had a poor outcome despite treatment with additional drugs.. A lower GCS and a higher rate of lesions on CT were identified as predictors of a prolonged course for HSVE. These predictors are in accordance with the conventional predictors of poor outcome for HSVE. This study suggests that the initial ACV treatment was insufficient for HSVE patients with these predictors at the acute stage. The initial treatment may need to be modified for such patients.

Topics: Acyclovir; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Glasgow Coma Scale; Humans; Japan; Male; Middle Aged; Prognosis; Risk Factors; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

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.. Retrospective chart review.. All four infants had abnormal neuroimaging studies and subsequently experienced severe developmental delay or death.. 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.

Topics: Acyclovir; Adult; Antiviral Agents; Atrophy; Brain; Brain Damage, Chronic; DNA, Viral; Dose-Response Relationship, Drug; Drug Administration Schedule; Encephalitis, Herpes Simplex; Encephalomalacia; Female; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Polymerase Chain Reaction; Pregnancy; Prognosis; Retrospective Studies; Simplexvirus; Tomography, X-Ray Computed; Viral Load

Topics: Acyclovir; Encephalitis, Herpes Simplex; Glasgow Coma Scale; Humans; Prognosis; Tomography, X-Ray Computed

A recent trial suggested that corticosteroid was beneficial in herpes simplex virus encephalitis (HSVE), but that precise role remains unclear. We assessed the differences of cerebrospinal fluid (CSF) cytokine changes between different outcomes and between patients with and without corticosteroid administration at the acute stage of HSVE. Interleukin (IL)-1beta, IL-2, IL-6, IL-10, interferon (IFN)-gamma, and tumor necrosis factor-alpha were measured in 56 serial CSFs taken from 20 adult HSVE patients. Their outcomes were poor in 7 and good in 13 patients, and corticosteroid was administered in 10. The differences in the initial and maximum cytokine values were assessed among the different outcomes. The decline rate of cytokine values between the initial and second CSF samples was also assessed between patients with and without corticosteroid. The initial IFN-gamma and maximum IL-6 with a poor outcome were higher than those with a good outcome (p=0.019 for IFN-gamma and p=0.013 for IL-6). The decline rate of IL-6 in patients with corticosteroid was higher than that without corticosteroid (p=0.034). The initial IFN-gamma and maximum IL-6 CSF values represented prognostic biomarkers in HSVE. One pharmacological mechanism related to corticosteroid in HSVE is apparently inhibition of pro-inflammatory cytokines such as IL-6.

Topics: Acyclovir; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Antiviral Agents; Biomarkers; Cytokines; Encephalitis, Herpes Simplex; Female; Humans; Interferon-gamma; Interleukin-6; Male; Middle Aged; Prognosis; Simplexvirus; Treatment Outcome; Young Adult

Herpes simplex encephalitis (HSE) is the most frequent cause of sporadic necrotizing encephalitis in adults. The aim of this study is to describe the characteristics of HSE and the factors influencing its outcome.. Retrospective study of patients diagnosed with HSE in a tertiary care teaching hospital over a 15-year period. Diagnosis was based on a consistent clinical profile for HSE, plus either a PCR-positive CSF HSV study or consistent brain neuroimaging findings. Patients were divided into 2 groups according to the modified Rankin Scale: good outcome (Grades <=2) and poor outcome (Grades >=3).. Thirty-five patients were included. Mean age was 53.9 years. More than half presented febricula or fever, headache, disorientation, behavioral changes, decreased level of consciousness, or neurological deficit. CSF glucose concentration was normal in all patients and WBC count was normal in 8 (23%). PCR for HSV was positive in 92% and cranial MRI was suggestive of HSE in 100% of patients. Mortality was 8.6%. In relation to outcome, age (OR=1.079; 95% CI, 1.023-1.138) and serum albumin level at admission (OR=0.87; 95% CI, 0.794-0.954) were independent prognostic factors at discharge. At 6 months, days of fever after initiation of acyclovir therapy (OR=1.219; 95% CI, 1.046-1.422) and serum albumin level at admission (OR=0.917; 95% CI, 0.87-0.967) were independent prognostic factors.. Normal brain MRI or detection of low CSF glucose concentration requires consideration of diagnoses other than HSE. Age, serum albumin level at admission, and days of fever after initiation of acyclovir therapy were independent prognostic factors of the disease.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Brain Damage, Chronic; Cerebrospinal Fluid; Dexamethasone; Diagnostic Imaging; Encephalitis, Herpes Simplex; Female; Hospital Mortality; Hospitals, University; Humans; Intracranial Hypertension; Male; Middle Aged; Prognosis; Retrospective Studies; Seizures; Spain

Topics: Acyclovir; Antiviral Agents; Brain Damage, Chronic; Cerebrospinal Fluid; Dose-Response Relationship, Drug; Drug Administration Schedule; Encephalitis, Herpes Simplex; Humans; Infant, Newborn; Neurologic Examination; Polymerase Chain Reaction; Predictive Value of Tests; Treatment Outcome; Viral Load

Herpes simplex encephalitis is a devastating disease. In the early 1980s our group conducted a nationwide clinical trial of acyclovir versus vidarabine in patients with herpes simplex encephalitis in whom intrathecal herpes simplex virus (HSV) antibodies were assayed. The purpose of this study was to investigate if antibody levels and viral load correlate with outcome in herpes simplex encephalitis. We have analysed the prognostic value of HSV antibody levels in serum and cerebrospinal fluid (CSF) at the start of antiviral treatment in the 53 included patients. Frozen samples from a subset of patients were analysed with quantitative polymerase chain reaction (PCR) to assess the prognostic value of the viral load in CSF. IgG-levels in CSF at presentation were significantly higher in vidarabine-treated patients with a favourable outcome than in those treated with vidarabine but with an unfavourable outcome. The intrathecal viral load at presentation showed no correlation with outcome. However, the duration of positive HSV-PCR in CSF was longer in vidarabine-treated than in acyclovir-treated patients. These findings indicate that the B-cell response is important in the pathogenetic process of herpes simplex encephalitis. However, neither antibody levels nor viral load at presentation are useful as prognostic markers for the individual patient in this study.

Topics: Acyclovir; Adolescent; Adult; Aged; Antibodies, Viral; Antibody Formation; Antiviral Agents; B-Lymphocytes; DNA, Viral; Encephalitis, Herpes Simplex; Female; Humans; Immunoglobulin G; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction; Predictive Value of Tests; Prognosis; Time Factors; Treatment Outcome; Vidarabine; Viral Load; Young Adult

Although herpes simplex virus type 1 (HSV-1) is the most common cause of sporadic encephalitis in immunocompetent adults, it is an unusual cause of encephalitis in patients with HIV/AIDS. We report the case of a 56-year-old man with recently diagnosed HIV infection who presented with subacute mental status changes, fever, and temporal lobe abnormalities evident on brain imaging. Results of a polymerase chain reaction assay of the cerebrospinal fluid were positive for HSV-1. His course was complicated by 2 episodes of cerebral hemorrhage. He ultimately improved after surgical decompression, treatment with acyclovir, and a switch from a protease inhibitor-based antiretroviral regimen to one including an integrase inhibitor.

Topics: Acyclovir; Antiviral Agents; Cerebral Hemorrhage; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; HIV Infections; Humans; Infusions, Intravenous; Male; Memory Disorders; Middle Aged; Seizures; Tomography, X-Ray Computed

Herpes simplex virus type 1 is a sporadic cause of viral encephalitis. Relapse of encephalitis occurs in up to 10% of patients, manifested by recurrent symptoms, clinical and MRI findings, and the presence of herpes simplex virus type 1 DNA in the cerebrospinal fluid (CSF).. We describe the clinical features, MRI findings and outcome in 2 patients with herpes simplex encephalitis during the acute phase and 6 months after the onset of encephalitis.. Both patients had a good response to treatment and an excellent recovery. Despite clinical recovery, in a 6-month follow-up MRI lesions consistent with recurrence were disclosed, without any clinical findings or CSF abnormalities.. The mechanism underlying this MRI deterioration is unclear and an immune-mediated mechanism may be involved. Thus, MRI deterioration after herpes simplex encephalitis should be interpreted with caution and it does not always represent a relapse, especially when the imaging studies do not correlate with the clinical and CSF findings.

Topics: Acyclovir; Anticonvulsants; Antiviral Agents; Brain; Cerebral Cortex; Chronic Disease; Disease Progression; Encephalitis, Herpes Simplex; Female; Frontal Lobe; Gyrus Cinguli; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Fibers, Myelinated; Recovery of Function; Recurrence; Retrospective Studies; Temporal Lobe; Tomography, X-Ray Computed; Treatment Outcome

Herpes simplex is a common human pathogen that has rare but severe manifestations including encephalitis.. A 44-year-old man underwent uneventful resection of an acoustic neuroma. Postoperatively, he developed swinging pyrexia, vomiting, and episodic confusion. Analysis of cerebrospinal fluid showed a lymphocytosis, and polymerase chain reaction revealed herpes simplex DNA. After treatment of herpes encephalitis with acyclovir, the patient made a good recovery.. Herpes encephalitis is a rare complication of neurosurgical procedures, and the most likely etiology is reactivation of latent infection from manipulation of cranial nerves.

Topics: Acyclovir; Adult; Antiviral Agents; Consciousness Disorders; DNA, Viral; Encephalitis, Herpes Simplex; Facial Nerve; Facial Nerve Diseases; Fever; Humans; Magnetic Resonance Imaging; Male; Neuroma, Acoustic; Neurosurgical Procedures; Recurrence; Simplexvirus; Tomography, X-Ray Computed; Vestibulocochlear Nerve; Vomiting

The outcome of herpes simplex virus (HSV) encephalitis is improved with prompt initiation of aciclovir treatment. Delays are common, but there is little understanding of why they occur. The case notes of 21 adults admitted with suspected HSV encephalitis over one year were reviewed. The median (range) duration of illness was 2.5 (1-99) days. Seventeen (81%) patients had a lumbar puncture (LP) performed, at a median (range) time of 24 (2-114) hours after encephalitis was suspected. Lumbar puncture was delayed for a computed tomography (CT) scan in 15 patients, but only one of these had contraindications to an immediate LP. The median (range) time from presentation to starting aciclovir was 48 (2-432) hours. HSV-PCR (polymerase chain reaction) was requested on cerebrospinal fluid from 12 patients, one of whom was positive. Five (24%) patients were given the wrong dose of aciclovir. Overall the management of suspected HSV encephalitis was often sub-optimal, with delays in LP occurring due to unnecessary CT scans, and the wrong aciclovir dose administered. Guidelines for the management of suspected encephalitis are needed.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Antiviral Agents; Brain; DNA, Viral; Encephalitis, Herpes Simplex; Female; Hospitals, Teaching; Humans; Male; Medication Errors; Middle Aged; Polymerase Chain Reaction; Retrospective Studies; Spinal Puncture; Time Factors; Tomography, X-Ray Computed; United Kingdom

We have successfully eliminated herpes simplex virus-2 from the central nervous system in a case of neonatal herpes simplex virus encephalitis with a continuous acyclovir infusion. A male infant delivered from a healthy 22-year-old woman without genital or systemic herpes symptoms around delivery began to develop fever and intractable seizures. He was started on intermittent intravenous acyclovir (20 mg/kg every 8 h) based on the diagnosis of herpes encephalitis. The virus was not eliminated with intermittent acyclovir and vidarabine, while continuous acyclovir was ultimately effective in eliminating herpes simplex virus from his central nervous system. This report demonstrates the efficacy of continuous acyclovir infusion in neonatal herpes simplex virus encephalitis.

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Infant, Newborn; Male; Young Adult

Topics: Acyclovir; Adult; Anti-Inflammatory Agents; Antiviral Agents; Dexamethasone; Encephalitis, Herpes Simplex; Female; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Term Birth

Herpes virus encephalitis is a rare, life-threatening complication of therapy in patients with brain tumors. A surgical therapeutic approach may be needed because the infection can be resistant to acyclovir in immunocompromised patients, and complications and long-term sequelae are frequent.. We present the case of a right-handed, 6-year-old girl with a brainstem tumor who had herpes virus encephalitis with refractory seizures while on immunosuppressive treatment. The virus was resistant to acyclovir but responded to gancyclovir. The patient developed local refractory brain edema with right uncal herniation.. To reduce the intracranial pressure, internal decompressive craniotomy was performed, which consisted of a right temporal lobectomy that allowed us to remove the focal necrotic-hemorrhagic tissue, decrease inflammation, and avoid subsequent chronic gliotic scarring. Clinical improvement was clear with prompt recovery and acute control of seizures. The only remaining deficits were mild memory and attention impairments. Seizures did not recur in the next 6 months.. Antiviral resistance should be suspected in immunocompromised patients with herpes virus encephalitis if there is no early response to acyclovir. If uncal herniation of the nondominant temporal lobe develops, temporal lobectomy, as an internal decompressive procedure, can be lifesaving. Lobectomy stopped the acute refractory seizures and can be considered a good approach to prevent later epilepsy, with only mild residual cognitive deficits.

Topics: Acyclovir; Anterior Temporal Lobectomy; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Brain Stem Neoplasms; Child; Electroencephalography; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Radiotherapy; Seizures; Temporal Lobe

A rare case of EBV encephalitis initially diagnosed as Herpes simplex infection is presented to highlight the importance of EBV specific intrathecal ELISA and liquor PCR based differential diagnosis when Herpes simplex encephalitis specific clinical symptoms, neuroimaging signs and electroencephalographic features are present. The case report also suggests that acyclovir treatment might be beneficial for the long term outcome in adult EBV encephalitis patients.

Topics: Acyclovir; Adult; Cerebrospinal Fluid; Diagnosis, Differential; Encephalitis, Herpes Simplex; Encephalitis, Viral; Enzyme-Linked Immunosorbent Assay; Epstein-Barr Virus Infections; Female; Head; Herpesvirus 4, Human; Humans; Polymerase Chain Reaction; Radiography; Treatment Outcome

Topics: Acyclovir; Aged; Cognition Disorders; Encephalitis, Herpes Simplex; Herpesvirus 2, Human; Humans; Magnetic Resonance Imaging; Male

Herpes simplex encephalitis (HSE) is a rare, life-threatening disease. This paper draws attention to the role of imaging in early HSE diagnosis. Five consecutive patients diagnosed with HSE (type 1) between June 2005 and June 2006 (three males, two females, mean age 44 [range 16-68] years) were included in this retrospective study. Computed tomography, conventional magnetic resonance imaging (MRI) sequences and diffusion-weighted imaging (DWI) were obtained for each patient. Apparent diffusion coefficient values were calculated in diseased and normal tissue. Therefore, we propose that MRI scan with DWI should be performed when HSE is suspected, although in disease follow-up DWI is not superior to conventional sequences. There is no need for contrast media to be administered at any disease stage. Fluid-attenuated inversion recovery is superior to T2 sequencing in showing cortical lesions at all disease stages.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Diffusion Magnetic Resonance Imaging; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male; Middle Aged; Polymerase Chain Reaction; Retrospective Studies; Treatment Outcome; Turkey

We report the story of a 81 year old man referred for confusion and unexplained hyperthermia. He had no meningeal sign. Routine emergency examinations (CT scanner and lumbar punction) were not contributory, but, later, PCR for herpes virus was highly positive and cerebral CT scan showed the temporal lobe necrosis typical of an herpes virus meningoencephalitis. This severe neurologic emergency is then shortly discussed.

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Confusion; DNA, Viral; Encephalitis, Herpes Simplex; Fever; Humans; Male; Polymerase Chain Reaction; Simplexvirus; Tomography, X-Ray Computed; Treatment Outcome

To investigate the clinical characteristics of herpes simplex encephalitis (HSE) and to discuss the mechanism of its relapse.. The clinical data of 6 patients with relapsing encephalitis, 4 male and 1 female, aged 14 - 49, out of 150 encephalitis cases were analyzed: 5 of them were suspected as with HSE clinically, and HSE was confirmed by pathology via biopsy in 2 of the 6 patients. The 5 patients were followed up for 2 - 6 years.. The duration between the onset and relapse was 1 - 26 months. Brain MRI or CT showed new lesions in the temporal lobe in 5 patients. Necropsy revealed intracellular inclusions, positive in HSV-1 antigen, in the neurons and glial cells of temporal lobe in one case. Second course of acyclovir therapy was effective in 5 of these 6 patients. One patient died 10 months later.. Direct invasion of activated virus into the central nervous system and insufficiency of acyclovir treatment are the causes of relapse of HSE. Acyclovir treatment should be early, with sufficient amount, and individualized.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Recurrence; Retrospective Studies; Temporal Lobe; Tomography, X-Ray Computed; Young Adult

A 61-year-old female developed left hemiparesis after the onset of high fever and a consciousness disturbance. Fluid attenuated inversion recovery (FLAIR) MR imaging showed high signal intensity lesions in the right temporal lobe, cingulate gyrus, and parietal lobe. Encephalitis caused by a herpes simplex virus (HSV) infection was suspected and the administration of intravenous aciclovir was thus immediately initiated. Her consciousness disturbance rapidly became exacerbated; however, the brain lesions progressively expanded to the midbrain and left hemisphere. The addition of intravenous high-dose corticosteroids to the treatment regimen ameliorated the consciousness disturbance. Although no HSV DNA was detected by repeated PCR using cerebrospinal fluid (CSF) specimens, real time PCR using a biopsied brain tissue specimens detected HSV type 1 DNA. A pathological examination showed destruction of the grey matter and a perivascular aggregation of lymphocytes, thus suggesting a diagnosis of necrotizing viral encephalitis. Immunohistochemical analysis did not reveal the presence of the HSV antigen. Hence, in the present patient failure of PCR or a serological diagnosis using CSF specimens can be ascribed to the paucity of viral particles in the brain. We therefore concluded that real-time PCR using biopsied brain tissue specimens is a novel, sensitive method for detecting causative agents in patient with prolonged and undiagnosed encephalitis.

Topics: Acyclovir; Adrenal Cortex Hormones; Biomarkers; Biopsy; Brain; DNA, Viral; Encephalitis, Herpes Simplex; Female; Humans; Infusions, Intravenous; Magnetic Resonance Imaging; Middle Aged; Polymerase Chain Reaction; Simplexvirus

Herpes simplex (HSV) encephalitis is a disease with a high mortality. HSV infections affect relatively young people. Characteristic neurological signs, MRI findings, PCR of cerebrospinal fluid (CSF) are useful tools in early recognition of HSV encephalitis. We present a case of HSV encephalitis with favourable course in 37-year-old woman in 26 week of pregnancy.

Topics: Acyclovir; Adult; Antiviral Agents; Early Diagnosis; Encephalitis, Herpes Simplex; Female; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Treatment Outcome; Triazines

We reviewed retrospectively the demographic, clinical, biological characteristics and outcomes of 11 patients with HSV meningitis.. Among the 11 patients, six were infected with HIV, four had a documented history of genital herpes, and one recurrent meningitis. In all cases, the onset of symptoms was abrupt, with severe headache and fever. On admission, 9/11 patients had severe meningismus; two patients had HSV anogenital ulcerations. CSF analysis showed in every case a significant increased of leukocytes with a lymphocytic pleocytosis, a mild elevated protein level and a normal glucose level. HSV was detected in the CSF in every case by PCR: the typing performed on six patients was positive in every case for HSV-2. Intravenous acyclovir (IV ACV) was started in 10/11 cases (range: 3-10 days), switched to valaciclovir (VACV) (range: 5-7 days); one patient was treated with ACV per os for 10 days. The total resolution of symptoms occurred within 48hours in every case. Two patients presented with recurrent HSV-2 meningitis in the next two months, with favorable outcome under IV ACV: a switch to long term VACV 500mg/day was prescribed without any recurrence. No patient presented with recurrence after a median follow-up of 30 months.. Early recognition and treatment might improve the outcome of such infections. Adjunctive oral VACV after IV ACV treatment seems to be associated with a good clinical response in patients presenting with HSV meningitis. The duration of such treatments, including prophylactic treatments to prevent recurrent episodes must be better documented.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Comorbidity; Disease Susceptibility; Encephalitis, Herpes Simplex; Female; Herpes Genitalis; Herpesvirus 2, Human; Hospitals, Urban; Humans; Male; Middle Aged; Paris; Recurrence; Retrospective Studies; Treatment Outcome; Valacyclovir; Valine

Topics: Acyclovir; Aged; Antineoplastic Agents; Antiviral Agents; Cerebrospinal Fluid; Colonic Neoplasms; Diabetes Mellitus, Type 2; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompromised Host; Male

Post-malaria neurological syndrome (PMNS) defined by a post-infective encephalopathy occurring within 2 months after an episode of Plasmodium falciparum infection is still a debated entity. We describe 2 cases of PMNS in 2 patients of African origin, born and living in France. Both patients had severe P. falciparum infection, followed by PMNS. They recovered with no sequelae. These are the first-reported cases of PMNS in patients of African ethnicity and living in France.

Topics: Acyclovir; Adolescent; Adult; Brain Diseases; Cote d'Ivoire; Encephalitis, Herpes Simplex; France; Gambia; Humans; Malaria, Falciparum; Male; Syndrome; Treatment Outcome

Topics: Acyclovir; Antiviral Agents; Child; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Thalamus

Topics: Acyclovir; Adult; Anticoagulants; Antiviral Agents; CD4 Lymphocyte Count; Encephalitis, Herpes Simplex; Headache; Heparin; Herpes Zoster Oticus; HIV Infections; HIV-1; Humans; Male; Radiography; Sinus Thrombosis, Intracranial; Thrombophilia; Viral Load

Herpes simplex encephalitis (HSE) can cause high mortality and morbidity in children. Since local data of HSE in children are rare, we performed a retrospective study to evaluate the prognostic factors and outcome of HSE in Taiwan.. Children were enrolled into this study if they were diagnosed as having encephalitis and also had positive polymerase chain reaction for herpes simplex virus (HSV) from cerebrospinal fluid, and/or positive immunoglobulin M or at least four-fold elevation of immunoglobulin G against HSV type 1 or type 2 from serum during the period from December 1, 1984 to January 31, 2003.. Forty patients were enrolled in this study. Twenty six patients (65%) had good outcome and 14 (35%) had poor outcome. No mortality or recurrence was found. Three-fifths of the patients were between 1 year and 6 years of age. Fever (75%) was the most common finding at admission, followed by seizures (63%), lethargy (60%), and altered consciousness (48%). Seizure and lethargy at the time of admission were more common in the poor outcome group (71% vs 58% and 64% vs 58%). Abnormal computed tomography/magnetic resonance imaging findings were found in 63% of patients in whom the examinations were performed. Abnormal electroencephalogram (EEG) findings were noted in 79% of tested patients. Acyclovir was used to treat 29 patients (73%). Abnormal neuroimaging or EEG findings were more prevalent in patients with poor outcome (75% vs 55% and 92% vs 71%), as well as delayed (>/=3 days) initiation of acyclovir therapy (92% vs 71%). There was no significant difference between the poor and good outcome groups in gender, age distribution, and clinical presentation.. As we cannot predict the outcome of patients with HSE in the early beginning of illness and delay of treatment may cause disaster, early diagnosis and prompt acyclovir initiation are important requirements for successful management.

Topics: Acyclovir; Adolescent; Antiviral Agents; Child; Child, Preschool; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Fever; Humans; Infant; Lethargy; Male; Retrospective Studies; Seizures; Taiwan; Treatment Outcome; Unconsciousness

Meningo-encephalitis is a set of threatening diseases. The treatment needs to be started quickly for pathogens such as herpes simplex virus type 1 or Listeria monocytogenes. Apart from these classical etiologies, many other diseases may induce meningo-encephalitis. We report the case of a patient, infected with HIV, who presented a history of meningo-encephalitis due to herpes simplex type 1. Three weeks later, he presented an encephalopathy due to aciclovir and then we discovered a chronic meningitis in relation with his HIV infection.

Topics: Acyclovir; Diagnosis, Differential; Encephalitis, Herpes Simplex; HIV Infections; Humans; Male; Meningoencephalitis; Middle Aged

Herpes simplex virus (HSV) is a common infection that occasionally presents with destructive lesions. Two of the most feared presentations of HSV are encephalitis and acute retinal necrosis. Although there are numerous reports of acute retinal necrosis presenting after HSV-2 infection in children, it has been rarely reported in children after HSV-1 infection. Herein we report a child who developed acute retinal necrosis 17 months after HSV-1 encephalitis.

Topics: Acyclovir; Antiviral Agents; Child, Preschool; DNA, Viral; Encephalitis, Herpes Simplex; Follow-Up Studies; Herpesvirus 1, Human; Humans; Laser Therapy; Male; Polymerase Chain Reaction; Retinal Detachment; Retinal Necrosis Syndrome, Acute; Vitrectomy

We report a 41-year-old man with meningoencephalitis associated with herpes simplex virus type 1 (HSV-1). The patient developed fever, headache and dysuria followed by generalized convulsion and neck stiffness, and the CSF showed pleocytosis. The titers of enzyme-linked immunosorbent assay against HSV measured 6 days after onset showed a significant rise; IgG antibody 4.89 (<0.2) and IgM antibody 1.45 (<0.8) in CSF, IgG antibody 46.1 (<2.0) and IgM antibody 1.76 (<0.8) in the serum. The antibody index for IgG was 0.50, and that for IgM was 4.2. CFS neutralization test showed HSV-1 antibody of x16 and HSV-2 antibody of

Topics: Acyclovir; Adult; Antibodies, Viral; Antiviral Agents; Cerebral Cortex; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Humans; Immunoglobulin G; Immunoglobulin M; Magnetic Resonance Imaging; Male

Topics: Acyclovir; Aged; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans

Topics: Acyclovir; Antiviral Agents; Drug Monitoring; Encephalitis, Herpes Simplex; Female; Humans; Male

A 16-month-old girl presented with herpes simplex virus type 1 encephalitis with involvement of bilateral parietofrontal lobes, left thalamus and cerebellum. She was treated with intravenous acyclovir. As her condition deteriorated, high-dose methylprednisolone was administered, resulting in remarkable improvement. This case suggests considering a short course of high-dose steroid therapy in severe herpes simplex encephalitis when there is clinical and radiologic deterioration in spite of appropriate antiviral therapy and decreasing viral load in the cerebrospinal fluid.

Topics: Acyclovir; Antiviral Agents; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Glucocorticoids; Herpesvirus 1, Human; Humans; Infant; Methylprednisolone

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Humans; Incidence; Retrospective Studies; Sensitivity and Specificity; Simplexvirus; Sweden

Topics: Acyclovir; Adenoma; Chemotherapy, Adjuvant; Cranial Irradiation; Dexamethasone; Encephalitis, Herpes Simplex; Humans; Immunocompromised Host; Male; Middle Aged; Neoplasm Recurrence, Local; Pituitary Neoplasms; Radiotherapy, Adjuvant

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.

Topics: Acyclovir; Antiviral Agents; Brain; Cerebrospinal Fluid; DNA, Viral; Drug Resistance, Viral; Encephalitis, Herpes Simplex; Erythrocyte Count; Female; Glucose; Humans; Infant; Magnetic Resonance Imaging; Simplexvirus; Treatment Failure

Herpes simplex encephalitis (HSE) is a serious viral infection with a high rate of mortality. The most commonly seen complications are behavioral changes, seizures and memory deficits. We report the case of a 37-year-old man with HSE in the right temporal lobe and a severe midline shift who was treated with acyclovir. The patient underwent anterior temporal lobe resection. Although HSE can cause permanent cognitive deficits, in this case, early surgical intervention minimized any deficit, as determined by detailed neuropsychological examination. Surgical decompression is indicated as early as possible in severe cases. This case report emphasizes the effect of surgical decompression for HSE on cognitive function, which has rarely been mentioned before.

Topics: Acyclovir; Adult; Antiviral Agents; Decompression, Surgical; Encephalitis, Herpes Simplex; Encephalocele; Humans; Intracranial Hypertension; Male; Neuropsychological Tests; Temporal Lobe; Treatment Outcome

A 5-year-old female presented with prolonged afebrile right-sided focal seizures, right brachio-facial paralysis, and dysarthria; consciousness was not altered. Fever appeared 20 hours after onset of neurological symptoms. At admission (day 1) cerebral computerized tomography and cerebrospinal fluid (CSF) analyses were normal including undetectable alpha-interferon (alpha-IFN) and negative herpes simplex virus (HSV) polymerase chain reaction (PCR). Acyclovir was started at a dosage of 60mg/kg/day for 21 days and neurological symptoms improved. Cerebral magnetic resonance imaging (MRI) showed lesions in the left thalamus and left parietal lobe. On day 8, CSF contained an elevated leukocyte count with a predominance of lymphocytes, but alpha-IFN and HSV DNA were still undetectable. Delayed intrathecal synthesis of specific anti-HSV antibodies was found on day 26 and confirmed herpes simplex encephalitis (HSE) diagnosis. Twenty months after this episode, the patient presented with a febrile meningeal syndrome. PCR detected HSV DNA in CSF and cerebral imaging showed a new left temporal lesion. At relapse onset, intrathecal synthesis of specific anti-HSV antibodies had disappeared. Acyclovir was started at a dosage of 60mg/kg/day for 21 days and neurological status improved. At discharge, neurological examination showed right hemiparesis and bucco-facial dyspraxia. Diagnostic problems of HSE diagnosis in children are highlighted. It is suggested that the premature disappearance of intrathecal synthesis of a specific anti-HSV antibody might play a permissive role in the resurgence of cerebral viral replication.

Topics: Acyclovir; Antiviral Agents; Child, Preschool; DNA, Viral; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Recurrence; Simplexvirus

We evaluate the frequency of empiric acyclovir administration to patients in the emergency department (ED) who are ultimately diagnosed with encephalitis.. We conducted an explicit retrospective medical record review of consecutive patients discharged with a final diagnosis of herpes simplex encephalitis or viral encephalitis not otherwise specified for the period 1993 to 2003. The frequency of ED administration of empiric acyclovir was measured for patients who met the inclusion criteria of fever, neuropsychiatric abnormality, and cerebrospinal fluid pleocytosis with a negative Gram's stain result in the ED.. Of the 90 patients reviewed, 24 (27%) met the inclusion criteria of fever, neuropsychiatric abnormality, and cerebrospinal fluid pleocytosis with a negative Gram's stain result in the ED. Of these 24 patients, 7 (29%) received empiric acyclovir in the ED, 6 (86%) patients after cerebrospinal fluid results were available, with a median time to administration of 1.5 hours (95% confidence interval [CI] 0 to 3.1 hours). The remaining 17 (71%) patients did not receive acyclovir in the ED, with median times of 16 hours (95% CI 7.5 to 44 hours) before initiation of acyclovir in inpatient settings.. The majority of patients in our institution who were ultimately diagnosed with encephalitis did not receive empiric acyclovir in the ED, despite clinical presentations consistent with encephalitis.

Topics: Acyclovir; Adult; Child; Child, Preschool; Drug Utilization; Emergency Medicine; Emergency Service, Hospital; Encephalitis, Herpes Simplex; Encephalitis, Viral; Female; Humans; Infant; Infant, Newborn; Los Angeles; Male; Medical Audit; Middle Aged; Retrospective Studies

Encephalitis presenting as a change in mental status can be challenging to recognize in the primary care setting. However, early detection via a low threshold of suspicion can be useful, leading in turn to early treatment and improved survival.. We present a case which we consider relevant to primary care practitioners. The patient in question presented with relatively mild mental status changes, progressing to confusion, dysnomia and delirium over a period of three days. While infection did not appear to be the leading cause on her differential diagnosis, she was found on extensive workup to have encephalitis caused by Herpes Simplex Virus type 1.. The case is instructive for general practitioners and other clinicians to maintain vigilance for central nervous system (CNS) infections which may present atypically.

Topics: Acyclovir; Antiviral Agents; Aphasia; Diagnosis, Differential; Disease Progression; Emergency Service, Hospital; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Middle Aged; Polymerase Chain Reaction

Nonconvulsive status epilepticus is a specific form of status epilepticus characterized by alteration in mental status and persistent seizure activity on EEG, with or without motor phenomena. Recognition of the consequences of nonconvulsive status epilepticus has attracted greater attention to this condition. We present a 24-year-old woman with epilepsy who developed nonconvulsive status epilepticus during pregnancy. Despite treatment with antiepileptic drugs, the seizures persisted and confusion deepened. Further workup to explain the etiology revealed the diagnosis as herpes encephalitis. She recovered completely by the third day of parenteral acyclovir administration. Herpes simplex encephalitis causing nonconvulsive status epilepticus in a pregnant, epileptic woman is an unfortunate and unusual condition, which was simultaneously complicated by the presence of multiple etiological factors.

Topics: Acyclovir; Adult; Antiviral Agents; Electroencephalography; Encephalitis, Herpes Simplex; Epilepsies, Partial; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Status Epilepticus

Herpetic meningoencephalitis is treated with acyclovir (15 mg/kg/8 h). This higher dosage enhance the risk of acute renal failure.. We report the case of a previously healthy 42 years old man treated by intravenous aciclovir 1g/8 h for a herpetic meningoencephalitis. He presented an acute renal failure and an acute confusional state at the end of the treatment. Renal function and neurologic status improved rapidly with increased hydration and stop of the antiviral therapy.. If acyclovir is usually well tolerated, there is also a risk of acute nephropathy, especially dose-dependent. We point out the need to monitor renal function when high dosage of acyclovir is indicated.

Topics: Acute Kidney Injury; Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Humans; Male

Neonatal herpes encephalitis is usually caused by herpes simplex virus type 2 and results in significant morbidity and mortality. Imaging diagnosis with ultrasound, computed tomography scan and conventional magnetic resonance imaging may be normal in the early course of the disease. In this case diffusion-weighted magnetic resonance imaging detected the disease process earlier and better than the conventional T2-weighted or fluid-attenuated inversion recovery imaging sequences. The use of diffusion-weighted magnetic resonance imaging in neonatal herpes encephalitis proved to be a useful tool in the early stage of the disease.

Topics: Acyclovir; Cerebral Palsy; Diffusion Magnetic Resonance Imaging; Encephalitis, Herpes Simplex; Female; Follow-Up Studies; Humans; Infant, Newborn; Pregnancy

A twelve-year-old female was admitted with history of high fever, recurrent vomiting and repeated convulsion for 2 days and altered consciousness for one day. Cranial CT scan showed intraparenchymal haemorrhage involving both temporal lobes and right basal ganglia region without mass effect. Serology was reactive against IGM HSV1. Injection acyclovir was started at a dose of 10 mg/kg 8 hourly intravenously. Patient regained consciousness on fourth day but speech was altered. Abnormal behavioural symptoms were noticed. EEG showed generalised spike and slow waves and sharp and slow wave discharge more in the temporal region. The patient was given clonidine and carbamazepine. She also received behavioural therapy and parental counselling. She was followed up for six months and maintaining well.

Topics: Acyclovir; Antiviral Agents; Carbamazepine; Child; Clonidine; Encephalitis, Herpes Simplex; Female; Humans; Kluver-Bucy Syndrome; Risk Factors

Derivatives of the herpes simplex thymidine kinase inhibitor HBPG [2-phenylamino-9-(4-hydroxybutyl)-6-oxopurine] have been synthesized and tested for inhibitory activity against recombinant enzymes (TK) from herpes simplex types 1 and 2 (HSV-1, HSV-2). The compounds inhibited phosphorylation of [3H]thymidine by both enzymes, but potencies differed quantitatively from those of HBPG and were generally greater for HSV-2 than HSV-1 TKs. Changes in inhibitory potency were generally consistent with the inhibitor/substrate binding site structure based on published X-ray structures of HSV-1 TK. In particular, several 9-(4-aminobutyl) analogues with bulky tertiary amino substituents were among the most potent inhibitors. Variable substrate assays showed that the most potent compound, 2-phenylamino-9-[4-(1-decahydroquinolyl)butyl]-6-oxopurine, was a competitive inhibitor, with Ki values of 0.03 and 0.005 microM against HSV-1 and HSV-2 TKs, respectively. The parent compound HBPG was uniquely active in viral infection models in mice, both against ocular HSV-2 reactivation and against HSV-1 and HSV-2 encephalitis. In assays lacking [3H]thymidine, HBPG was found to be an efficient substrate for the enzymes. The ability of the TKs to phosphorylate HBPG may relate to its antiherpetic activity in vivo.

Topics: Animals; Antiviral Agents; Cloning, Molecular; Encephalitis, Herpes Simplex; Eye Infections, Viral; Guanine; Herpesvirus 1, Human; Herpesvirus 2, Human; Mice; Phosphorylation; Purinones; Recombinant Proteins; Structure-Activity Relationship; Thymidine Kinase; Virus Activation

Mortality and morbidity rates remain high among patients with herpes simplex virus encephalitis (HSVE). Chemokine-mediated recruitment and activation of leukocytes to focal areas of viral CNS infection are crucial steps in antiviral response and clearance. However, the inflammatory reaction and cellular antiviral response may enhance collateral damage to neurons and account for chronic progressive brain damage. We identified a specific mRNA expression of the interferon-gamma-inducible chemokines (CXCL9, CXCL10 and CXCL11), and RANTES (CCL5) in the acute course and long-term of experimental HSVE. This pattern was substantially altered by anti-viral and anti-inflammatory treatment. Our findings indicate a pivotal role of these chemokines in the immunopathogenesis of HSVE.

Topics: Acyclovir; Animals; Anti-Inflammatory Agents; Antiviral Agents; Chemokines; Disease Models, Animal; Drug Interactions; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Gene Expression Regulation; Methylprednisolone; Mice; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Viral Load

Topics: Acyclovir; Administration, Oral; Adsorption; Antiviral Agents; DNA, Viral; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; Polymerase Chain Reaction; Recurrence; Spinal Puncture; Virus Replication

Cutaneous herpes simplex virus type 2 (HSV-2) infection was recognized at 19 days of age in a 1415-g female infant born at 31 weeks of gestation. Cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) was negative, and MRI of the brain was normal. After a 14-day course of high-dose intravenous acyclovir, the infant developed a cutaneous recurrence at 38 days of age. CSF HSV PCR again was negative. She was subsequently begun on oral acyclovir to prevent cutaneous reactivation of HSV. At 3 months of age, the infant developed HSV encephalitis as manifested by fever, seizures, abnormal CSF indices, abnormal brain MRI, and positive CSF HSV PCR. No cutaneous disease was present. It is not known whether the HSV encephalitis in our patient represented reactivation of previously unrecognized central nervous system infection or new onset of central nervous system disease as a result of spread from other tissue or site to the brain. The failure of oral acyclovir to prevent such an occurrence, however, highlights gaps in our understanding of the pathogenesis of neonatal HSV disease and questions the use of acyclovir suppression to prevent neurologic sequelae.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Brain; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Injections, Intravenous; Magnetic Resonance Imaging; Polymerase Chain Reaction; Radiography; Recurrence; Seizures; Virus Activation

Topics: Acyclovir; Anticonvulsants; Child, Preschool; Drug Interactions; Encephalitis, Herpes Simplex; Humans; Male; Phenytoin; Valproic Acid

Encephalitis by herpes simplex virus (HSV) is an sporadic and the most important cause of encephalitis in the western world. The aim of this study was to describe the main clinical features and response to therapy in a representative series of cases. Fifteen cases confirmed by polymerase chain reaction were identified in two university hospitals in Santiago. Average age was 41 years (range 5-78) being 80% over 30 years old. Most cases presented with fever and sensorial involvement (80%) or headache (67%) and only a minority with seizures or focal signs (< or =15%). Extracerebral herpetic lesions were present in two patients (13%). Average length of symptoms was 3. 8 days and most cases were associated to type 1 HSV (86.7%). Changes were detected in 91.7% of those evaluated with electroencephalogram, in 81.8% of those evaluated with nuclear magnetic resonance and in only 13.3% of those evaluated with a cerebral CT-scan. All patients were treated with acyclovir and case-fatality ratio was 13.3%, although one death in a patient with AIDS and CNS lymphoma could not be related to HSV. Six patients (40%) showed neurological deficit at discharge. Death or neurological deficit at discharge was associated with a delay > 3 days before acyclovir therapy. (p = 0.01, two-tailed Fisher test).

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Child; Child, Preschool; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male; Middle Aged; Polymerase Chain Reaction

Topics: Acyclovir; Adult; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Migraine without Aura; Serotonin Receptor Agonists; Sumatriptan

Topics: Acyclovir; Adult; Encephalitis, Herpes Simplex; Female; Humans; Infant, Newborn; Magnetic Resonance Imaging; Pregnancy; Pregnancy Complications, Infectious

A 71-year-old woman with hypertension and hypothyroidism was transferred to our hospital from a nearby hospital because of right thalamic hemorrhage evident on CT. She had been suffered from fever and headache for five days. Neurological examination on admission revealed somnolence, rigidity in the neck and extremities, and bilateral Babinski signs. Then she developed decorticate rigidity in a day. On brain MRI four hours after admission, T2-hyperintese lesions were demonstrated in the bilateral thalamus in addition to hemorrhagic change of the right thalamus on the initial CT. No pleocytosis was evident on cerebrospinal fluid examination at admission. Follow-up MRI on the fifth hospital day, however, revealed expansion of the lesions bilaterally to the medial temporal lobes including amygdala, hippocampus and insular cortex. The diagnosis of herpes simplex encephalitis was established by PCR of cerebrospinal fluid on the same day. After immediate treatment with acyclovir and ara-A, she gradually became conscious and could respond to simple conversation. This was an unusual case of herpes simplex encephalitis originating from bilateral thalamic lesions on brain imaging. We should consider thalamus as a primary lesion in herpes simplex encephalitis.

Topics: Acyclovir; Aged; Antiviral Agents; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Humans; Intracranial Hemorrhage, Hypertensive; Magnetic Resonance Imaging; Thalamic Diseases; Thalamus; Vidarabine

Topics: Acyclovir; Adult; Antigens, Viral; Brain; Cerebral Arteries; DNA, Viral; Early Diagnosis; Encephalitis, Herpes Simplex; Female; Frontal Lobe; Headache; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Meninges; Neurons; Seizures; Temporal Lobe; Tomography, X-Ray Computed; Treatment Outcome

Viral encephalitis is associated with significant morbidity and mortality, particularly when appropriate management is omitted as a result of delayed diagnosis. A case of herpes simplex virus type 1 (HSV-1) encephalitis is presented, demonstrating that the presentation of confusion, speech difficulties and fever with non-specific early brain CT appearances can easily be misdiagnosed as pneumonia with stroke. This case highlights the need for increased awareness of HSV-1 encephalitis among emergency physicians and radiologists, given that the early spectrum of clinical and CT findings can mimic the more common diagnoses of sepsis and stroke.

Topics: Acyclovir; Aged, 80 and over; Confusion; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Stroke; Treatment Outcome

Herpes virus hepatitis (HSV) represents a form of acute necrotizing hepatitis, which most frequently develops in immunocompromised patients. Therapeutic options include high-dose intravenous acyclovir and liver transplantation. We report the first case of recurrent HSV hepatitis after liver retransplantation, which occurred despite continuous administration of high-dose intravenous antiviral therapy. Because explant histology pointed to initial therapy response, we thought that the reason for recurrence might be due to acyclovir resistance. Most acyclovir resistance is caused by inactivating mutations in the herpes virus thymidine kinase gene. HSV infection was detected by histology and proofed by immunohistochemistry. PCR amplification of the herpes virus thymidine kinase gene was performed on histology specimens to demonstrate the course of viral infection in liver tissue. Genotypic resistance testing of the herpes virus was performed by sequencing the thymidine kinase amplicon. In serial biopsy, HSV-DNA sequences were only detectable when histology revealed herpes hepatitis. Whereas the primary explant exhibited the wild-type thymidine kinase gene, a biopsy of the second graft one month after retransplantation, which showed recurrent herpes virus hepatitis, had a single base insertion within a homopolymeric cytosine stretch. This mutation causes a frame shift leading to a premature stop codon and results in a known acyclovir-resistant herpes strain. In conclusion, we believe that testing for acyclovir-resistant herpes strains should be considered in high-risk patients in whom viral clearance is not achieved serologically to prevent fatal recurrence of disease by using antiviral drugs such as inhibitors of HSV-DNA polymerase or viral helicase primase inhibitors.

Topics: Acyclovir; Amino Acid Sequence; Antiviral Agents; Base Sequence; Biopsy; DNA Primers; DNA, Viral; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Liver Cirrhosis, Alcoholic; Liver Transplantation; Male; Middle Aged; Polymerase Chain Reaction; Recurrence; Simplexvirus

Topics: Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Brain; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Glasgow Coma Scale; Humans; Logistic Models; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies; Treatment Outcome

Herpes simplex virus encephalitis (HSVE) is associated with significant morbidity and mortality, even with appropriate antiviral therapy. In the present investigation, the first to assess efficacy of corticosteroid treatment with aciclovir therapy in HSVE, multiple logistic regression analysis was performed of predictors of outcome in adult patients with HSVE.. A non-randomised retrospective study of 45 patients with HSVE treated with aciclovir was conducted. The patients were divided into poor and good groups based on outcome at three months after completion of aciclovir treatment. The variables evaluated were: clinical variables (sex, age, days after onset at initiation of aciclovir, Glasgow Coma Scale (GCS) at initiation of aciclovir, initial and maximum values for the cell numbers and protein concentration in the cerebrospinal fluid, and corticosteroid administration); neuroradiological variables (detection of lesions by initial cranial computed tomography and by initial magnetic resonance imaging); and one neurophysiological variable (detection of periodic lateralised epileptiform discharges on the initial electroencephalogram). Single variable logistic regression analysis was performed followed by multiple logistic regression analysis. The best set of predictors for the outcome of HSVE was estimated by stepwise logistic regression analysis.. A poor outcome was evident with older age, lower GCS score at initiation of aciclovir, and no administration of corticosteroid. Patient age, GCS at initiation of aciclovir, and corticosteroid administration were found to be significant independent predictors of outcome on multiple logistic regression analysis, and these three variables also formed the best set of predictors (R(2) = 0.594, p<0.0001).. Combination therapy using both aciclovir and corticosteroid represents one of the predictors of outcome in HSVE.

Topics: Acyclovir; Adult; Aged; Anti-Inflammatory Agents; Antiviral Agents; Brain; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Treatment Outcome

Topics: Acyclovir; Brain; Brain Edema; Craniotomy; Decompression, Surgical; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Immunocompromised Host; Immunosuppressive Agents; Magnetic Resonance Imaging; Meningioma; Middle Aged; Postoperative Complications; Steroids; Stress, Physiological; Treatment Outcome; Unconsciousness

Herpes simplex viruses (HSV), and especially HSV-1, are the most common cause of acute, sporadic viral encephalitis. HSV-2 is an uncommon cause of encephalitis. We report a rare case of HSV-2 encephalitis that was free of genital lesions. In terms of the patient's case history, she had a Cesarean section four months before, herpes labialis 30 days before, varicella zoster 20 days before. We discuss the possibility that postpartum stress may be one of the factors in this case.

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Herpesvirus 2, Human; Humans; Treatment Outcome

We report the case of a 53-year-old woman with uveitis in her right eye. She suffered from meningoencephalitis two years before. In the ophthalmic examination she showed no light perception, mild anterior uveitis and severe vitritis, which prevented from visualizing the retina. We suspected herpetic acute retinal necrosis (ARN), so therapy with intravenous acyclovir was started and a diagnostic vitrectomy was performed. Peripheral retinal necrosis and pallor of the optic disc were observed. PCR of the vitreous was positive for herpes simplex virus type I.. This is probably a case of brain-to-eye virus transmission. According to this, the ARN would support the etiologic suspicion of the previous encephalitis.

Topics: Acyclovir; Antiviral Agents; Blindness; Diagnosis, Differential; DNA, Viral; Encephalitis, Herpes Simplex; Eye Infections, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Middle Aged; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute; Vitreous Body

Topics: Acyclovir; Aged; Aged, 80 and over; Antiviral Agents; DNA, Viral; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Polymerase Chain Reaction; Treatment Outcome

Actinomycosis is a subacute or chronic bacterial infection, which can affect immunocompetent or immunodeficient subjects. It most often occurs in cervico-facial or thoracic-abdominal locations. Central nervous system infection is rare but of severe prognosis.. A 56 year-old woman with no history of immunodepression was admitted with unexplained fever, inappropriate behaviour, and spatial and temporal disorientation. The progressive worsening of the neurological signs let to coma and mechanical ventilation was required. Brain imaging showed multilocation cerebral abscesses. Stereotaxial biopsy permitted diagnosis of actinomycosis. Patient's outcome was favourable following appropriate dual antibiotherapy without surgical exeresis.. When lacking bacteriologic identification, diagnosis of cerebral actinomycosis is performed by pathologic findings. Dual antibiotherapy allows full recover, even in the case of multilocation cerebral abscesses.

Topics: Actinomyces; Actinomycosis; Acyclovir; Amoxicillin; Biopsy; Brain Abscess; Chloramphenicol; Clindamycin; Coma; Diagnostic Errors; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Fever; Humans; Listeriosis; Magnetic Resonance Imaging; Meningoencephalitis; Middle Aged; Nocardia Infections; Remission Induction; Tuberculosis, Meningeal

The combination of both PCR and intrathecal antibody studies is recommended to confirm or refute the diagnosis of herpes simplex encephalitis (HSE).. To investigate the pattern of use of laboratory tests in the diagnosis of suspected cases of HSE, and to determine the final diagnosis in cases proven not to be HSE.. Structured audit.. We reviewed the case-notes of all patients who, over a five-year time period, presented with suspected encephalitis; and/or were prescribed aciclovir. Clinical and laboratory criteria were used to categorize the likelihood of HSE.. We identified 222 patients: 10 (5%) had definite HSE, 24 (10%) possible HSE, and 144 (65%) a definite alternative diagnosis. In 44 (20%), no final diagnosis was made, but the diagnosis of HSE was excluded. PCR was performed in 68 (31%), intrathecal antibody studies in 24 (11%), and brain biopsy in 17 (8%). A wide range of diseases mimicked HSE, but most common were inflammatory diseases and other infections of the central nervous system.. Laboratory tests, particularly intrathecal antibody assays, are under-used in the diagnosis of HSE. Although early empirical treatment of suspected HSE is essential, confirmation or exclusion of the diagnosis is equally important to avoid overlooking alternative diagnoses. Identification of the aetiology of encephalitis is of particular importance, given the current concerns of emerging infections and bioterrorism.

Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; Brain; Diagnosis, Differential; Encephalitis, Herpes Simplex; Genes, Viral; Humans; Medical Audit; Polymerase Chain Reaction; Predictive Value of Tests; Retrospective Studies; Simplexvirus

Herpes simplex virus encephalitis (HSVE) is associated with a high mortality rate and a high probability of neurological sequelae. Good results are obtained when HSVE is promptly diagnosed and treated with acyclovir. We present a 71-year-old woman with clinically diagnosed HSVE, confirmed by PCR detection of HSV-1 DNA in the cerebrospinal fluid. She was treated with acyclovir (30 mg/kg day) for two weeks. Clinical and neuropsychological assessments 6 months after admission were normal; however MRI at 2, 6 and 12 months showed progressive deterioration with extensive white matter and cortical damage. Imaging studies of a cohort of patients surviving PCR-confirmed HSVE are needed to determine whether this pattern is occasional or a frequent form of progression.

Topics: Acyclovir; Aged; Antiviral Agents; Cerebral Cortex; Cognition; Disease Progression; DNA, Viral; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Nerve Degeneration; Neuropsychological Tests

Adverse neurological and renal effects can occur in patients taking acyclovir. Neurotoxicity of acyclovir results from an accumulation of the antiviral and its metabolites in the bloodstream. This can be observed in the elderly or in patients with chronic renal failure, generally in dialysis patients. Acute renal failure results from intratubular crystallization of acyclovir.. A 78-year-old right-handed woman was admitted in an emergency setting for aphasia. Analysis of the cerebrospinal fluid was normal, but herpetic meningo-encephalitis was suspected and intravenous treatment was initiated with acyclovir. After the second infusion, the patient began to suffer from visual hallucinations, confusion and acute renal failure. Herpes PCR was negative in the cerebrospinal fluid, and the adverse drug reactions regressed completely after 72 hours.. Renal function has to be checked often in patients given acyclovir for appropriate dose titration. Patients recover prompt from the adverse effects at drug withdrawal.

Topics: Acute Disease; Acyclovir; Aged; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Neurotoxicity Syndromes; Renal Insufficiency

The etiology of stroke in young patients is often unknown. Although systemic infections as well as specific infection agents, like herpes zoster virus or cysticercus, are often considered as risk factors, there are no indications that herpes simplex type 1 plays a role in the pathogenesis of stroke. We present the case of a young patient who suffered a stroke during a meningoencephalitis due to herpes simplex 1 and we review the relevant literature for a possible relation between the two entities.

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Male; Meningoencephalitis; Stroke

We assessed the potential for estimating the effects of antiviral therapy on the clearance of intrathecal herpes simplex virus (HSV) antigens as evaluated by the chemiluminescence assay (CL) and on that of intrathecal HSV-DNA as evaluated by the nested polymerase chain reaction (PCR) in serial patients with herpes simplex virus encephalitis (HSVE).. The materials comprised serial cerebrospinal fluid (CSF) samples from 18 patients with HSVE. All patients were diagnosed as having HSVE retrospectively based on the detection of intrathecal HSV antigens by the CL, that of HSV-DNA by the nested PCR, and also serological confirmation of intrathecal antibody production. The relationships between the days of aciclovir therapy and serial HSV viral loads as evaluated by the CL and nested PCR in the serial CSFs were assessed.. The serial intrathecal viral loads evaluated by the CL and nested PCR declined after the commencement of aciclovir administration in all patients. The serial alterations of the intrathecal viral load evaluated by the CL in each patient were similar to those of the intrathecal viral load evaluated by the nested PCR. The initial and maximum viral loads evaluated by the CL and nested PCR showed a wide distribution in the CSF samples taken from the patients with poor and good outcomes. Differences in the means of the viral loads in the CSF samples taken from the patients between a poor outcome and a good outcome were not evident. A transient increase of viral load as evaluated by these two methods was noted in the same 4 patients. The viral loads in these 4 patients also declined in the subsequent CSF samples. The outcome of these 4 patients was good in one patient and poor in the others.. Evaluation of intrathecal viral antigens by the CL has a potential for estimating the effects of antiviral therapy, as does evaluation of the intrathecal HSV-DNA by the nested PCR. The intrathecal viral loads evaluated by CL and nested PCR were not a predictor of outcome in HSVE.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Cerebrospinal Fluid; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Humans; Luminescent Measurements; Middle Aged; Polymerase Chain Reaction; Viral Load

Acute retinal necrosis syndrome (ARN syndrome) is a rare viral disease with a poor prognosis in most cases. It is characterized by substantial ocular inflammation with progressive retinal necrosis, occlusive vasculitis and sometimes extraocular features.. We report the case of a 62-year-old woman who was referred for a suspicion of a stroke. Ophthalmological examination revealed a profound bilateral visual loss due to extensive retinal necrosis. The patient was immediately treated with antiherpetic drugs. ARN syndrome with meningoencephalitis caused by herpes simplex virus type 2 was confirmed by PCR studies performed on aqueous humor and cerebrospinal fluid. Herpes simplex virus 2 (IgG+ , IgM-) was probably reactivated after intrathecal injection of steroids because of pain associated with narrowing of the lumbar vertebral canal. The patient was treated with intravenous Acyclovir for 3 weeks. After 4 months, both retinas were detached.. ARN syndrome caused by herpes simplex virus 2 most often occurs after reactivation of the latent virus in patients with a neurological medical history or congenital infection. Antiviral treatment must begin early to decrease risks of bilateralization and complications.

Topics: Acyclovir; Antiviral Agents; Aqueous Humor; Cerebrospinal Fluid; Dexamethasone; Diagnostic Errors; DNA, Viral; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Ganciclovir; Hemiplegia; Herpesvirus 2, Human; Humans; Magnetic Resonance Imaging; Middle Aged; Polymerase Chain Reaction; Retinal Detachment; Retinal Necrosis Syndrome, Acute; Stroke; Urinary Incontinence; Virus Activation

High index of suspicion is mandatory for early diagnosis of Herpes Simplex Encephalitis (HSE), since acyclovir therapy can prevent its mortality and limit morbidity. We report our observations on clinical spectrum, pitfalls in diagnosis and therapeutic aspects in patients of HSE.. There were 34 patients of HSE (26 males and eight females) in age range 6 -72 (mean 23.8 +/- 8.9) years. Diagnosis was confirmed by cranial MRI, EEG and PCR in CSF. Acyclovir was given to 24 patients. Carbamazepine and sodium valproate were the antiepileptic drugs used.. Most of the patients were referred either as Japanese encephalitis, cerebral malaria or tubercular meningitis. High fever, seizures, behavioral abnormality and encephalopathy were present in all, either at onset or later. EEG, CSF abnormality and cranial MRI were abnormal in all 34 patients. PCR for Herpes Simplex virus was positive in 65 % cases CT was performed in 10 cases but abnormality was detected only in four. We observed features of Kluver Bucy syndrome in three patients, suffering from HSE. Following complete acyclovir therapy in 24 patients, 12 recovered completely and four partially. There was no improvement in four patients including two patients who had features of Kluver Bucy Syndrome, while four expired. Among the seven patients who refused therapy of acyclovir, five expired, while two remained in unaltered status. Treatment could not be completed in three patients as they expired during therapy.. HSE is commonly misdiagnosed. Important factors influencing mortality and morbidity of HSE were; early acyclovir therapy, age, immune status of patient, duration of illness, and consciousness level before initiation of therapy. We conclude that acyclovir should be given to all patients as soon as suspected, while confirmatory investigations are in progress.

Topics: Acyclovir; Adolescent; Adult; Aged; Child; Diagnosis, Differential; Electroencephalography; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Sex Distribution; Treatment Outcome

Topics: Acyclovir; Adolescent; Antibodies, Viral; Brain; Cerebral Cortex; Demyelinating Autoimmune Diseases, CNS; Diagnosis, Differential; Encephalitis, Herpes Simplex; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Polymerase Chain Reaction; Prednisolone; Recurrence; Simplexvirus; Tomography, X-Ray Computed; Virus Activation

Relapses of herpes simplex encephalitis (HSE) occurring after the completion of antiviral treatment have been reported repeatedly in children. The authors report data on six children who had at least one relapse of HSE. Two different mechanisms may account for these relapses, including viral replication or an immuno-inflammatory process, with different therapeutic attitudes. Relapses with viral replication may reveal host susceptibility to herpes simplex virus infection.

Topics: Acyclovir; Adolescent; Antiviral Agents; Basal Ganglia Diseases; Child; Child, Preschool; Encephalitis, Herpes Simplex; Female; Follow-Up Studies; Humans; Infant; Male; Recurrence; Retrospective Studies

Topics: Acyclovir; Adolescent; Antibodies, Viral; Encephalitis, Herpes Simplex; Globus Pallidus; Herpesvirus 1, Human; Humans; Male; Tomography, X-Ray Computed

A 27 year old woman developed a vesicular genital rash and cerebellar dysfunction with progressive neurological deterioration suggesting brain stem encephalitis. Respiratory support was required. Magnetic resonance imaging (MRI) of the brain on day 7 showed signal hyperintensity in the central medulla and ventral pons, typical of acute inflammation. The course was severe and relapse occurred. MRI on day 33 showed a haemorrhagic area in the medulla. Treatment with aciclovir/valaciclovir eventually led to gradual recovery. Herpes simplex virus 2 (HSV-2) DNA was detected in CSF on days 11 and 14. HSV-2 was also detected in vesicle fluid from the genital rash. Serum was initially negative for HSV-1 and HSV-2 antibodies, but convalescent samples showed seroconversion to HSV-2, indicating primary infection. Intrathecal synthesis of oligoclonal IgG bands specific for HSV was identified in the CSF. It is important to differentiate HSV-2 from HSV-1, and primary from initial or reactivated infection, so that prolonged aciclovir treatment followed by prophylaxis is instituted to prevent the high likelihood of symptomatic relapse in primary HSV-2 infection.

Topics: Acyclovir; Adult; Antiviral Agents; Brain Stem; DNA, Viral; Encephalitis, Herpes Simplex; Female; Herpesvirus 2, Human; Humans; Immunoglobulin G; Magnetic Resonance Imaging

A 34-year-old woman who presented with only severe headache for 12 days was reported. She was initially diagnosed with cerebral infarction of the right temporal lobe and treated with aspirin, without improvement. On admission, she had bilateral papilledema. Other findings were unremarkable. CT scan and MRI of the brain revealed an area of cerebritis at the right temporal lobe. Lumbar puncture showed high opening pressure with normal CSF profiles. The patient was treated with intravenous acyclovir which gave a favorable outcome.

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Thailand; Tomography, X-Ray Computed

Management of herpes simplex encephalitis (HSE) has been considerably improved by the availability of acyclovir therapy and rapid polymerase chain reaction (PCR)-based diagnostic assays. Prognostic factors for this rare affliction are, however, misestimated. We conducted a large retrospective multicenter study that included 93 adult patients in whom HSE was diagnosed by PCR from 1991 through 1998 and who were treated with intravenous acyclovir. Among the 85 patients assessed at 6 months, 30 (35%) had a poor outcome, which led to death in 13 patients (15%) and severe disability in 17 (20%). The outcome was favorable for 55 patients (65%). A multivariate analysis identified 2 factors that were found to be independently associated with poor outcome: a Simplified Acute Physiology Score II >/=27 at admission and a delay of >2 days between admission to the hospital and initiation of acyclovir therapy. Early administration of antiviral therapy is the only parameter that can be modified to improve the prognosis of patients with HSE.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Brain; Encephalitis, Herpes Simplex; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Prognosis; Radiography; Retrospective Studies; Treatment Outcome

Topics: Acyclovir; Adult; Antigens, Viral; Antiviral Agents; Biopsy; Cerebrospinal Fluid; Child; Drug Administration Schedule; Encephalitis, Herpes Simplex; Ganciclovir; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Olfactory Pathways; Polymerase Chain Reaction; Temporal Lobe; Trigeminal Ganglion

We describe a 14-month-old patient with atypical presentation of herpes simplex encephalitis. She initially presented with fever, lethargy, seizures, and large hemorrhages in the right parietal lobe, and clinical findings suggestive of a hypercoagulable state. The etiology of coagulation abnormality was not identified, although it was suggested as a possible causative factor in severe bleeding along with acute neuronal lysis as a result of infection. Although large intracerebral hemorrhages are occasionally described with systemic herpes infection, this presentation is unusual beyond the infant period.

Topics: Acyclovir; Adolescent; Blood Coagulation Tests; Cerebral Cortex; Cerebral Hemorrhage; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Magnetic Resonance Imaging; Neurologic Examination; Polymerase Chain Reaction; Pregnancy; Tomography, X-Ray Computed

We described a 58-year-old woman with herpes simplex encephalitis (HSE), who initially had fever and developed impaired consciousness. Cerebrospinal fluid (CSF) examination showed mononuclear pleocytosis and the existence of herpes simplex virus (HSV) DNA. The first T1-weighted MR image showed symmetrical swelling and low signal intensity lesions in the medial temporal lobes and hippocampus. T2-weighted MR image showed high signal intensity lesions in the medial temporal lobes, the amygdala, the hippocampus, the insula and the cingulate gyri bilaterally. After the treatment with intravenous acyclovir and betamethasone, impaired consciousness and recent memory disturbance gradually improved. On the second T1-weighted MR image examination, eighteen days after the onset, high signal intensity lesions were demonstrated in the right medial temporal lobe, the right hippocampus, the left insula and the bilateral cingulate gyri. Although the clinical symptoms had improved significantly over three months, the high signal intense lesions on T1-weighted MR images were also detected in the left medial temporal lobe, the right insula, and the straight gyrus. Brain CT did not demonstrate any abnormalities. The repeated CSF examinations showed negative HSV DNA and a decreased number of WBC. However, oligoclonal IgG bands were continuously positive. Myelin basic protein level and IgG index increased in parallel with the expansion of the cerebral lesions on T1-weighted MR images. In the present case, the abnormality of T1-weighted MRI was thought to indicate hemorrhagic inflammatory lesions that could not be detected by CT. The increased level of myelin basic protein, the elevated IgG index and the continuous positive oligoclonal IgG indicated continuous immunologic response against HSV in these lesions.

Topics: Acyclovir; Betamethasone; Cerebral Cortex; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Middle Aged

In the brain tissue of 36 mice infected with herpes simplex virus type 1, strain F, we determined the expression of inducible nitric oxide synthase (iNOS) with semiquantitative reverse transcription polymerase chain reaction. The viral burden was quantitated by polymerase chain reaction. Nitric oxide, induced by iNOS, may contribute to neuronal cell damage following virus infection. As the experimental therapeutic strategy in herpes simplex virus encephalitis (HSVE), we used: N-nitro-L-arginin (L-NA), a selective inhibitor of iNOS; and combination therapies of either methylprednisolone/acyclovir or L-NA/acyclovir. The viral burden peaked in acute disease, and then returned to a low baseline value, except in untreated controls. The expression of iNOS mRNA was suppressed by L-NA and by acyclovir/corticosteroids. INOS inhibition may provide an additional therapeutic strategy targeted specifically to suppress iNOS expression as a potential secondary mechanism of tissue damage in acute and chronic HSVE.

Topics: Acyclovir; Animals; Antiviral Agents; Brain; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Enzyme Inhibitors; Female; Gene Expression Regulation, Enzymologic; Herpesvirus 1, Human; Methylprednisolone; Mice; Mice, Inbred Strains; Neuroprotective Agents; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitroarginine; Viral Load

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.. 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.. 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.

Topics: Acyclovir; Adult; Antiviral Agents; Brain; Decompression, Surgical; Encephalitis, Herpes Simplex; Female; Humans; Male; Microscopy, Electron; Middle Aged; Neurosurgical Procedures; Tomography, X-Ray Computed

To evaluate the usefulness of a rapid and simple PCR method in the diagnosis of herpetic meningoencephalitis in a pediatric population.. One hundred twenty-three cerebrospinal fluid samples from 114 pediatric patients attending the Hospital Sant Joan de Déu in Barcelona for clinical suspicion of viral meningoencephalitis or to rule out a possible herpetic etiology were evaluated. In addition to classical methods, the diagnostic technique used was PCR amplification of a highly preserved region of the DNA polymerase gene common to herpes virus 1 and 2. All patients were administered acyclovir on admission and until the results of PCR were known. If the result was negative, withdrawal of acyclovir was considered after clinical reexamination. If the result was positive, the therapy was continued for 20 days.. Herpes simplex DNA was detected in four patients. In all patients, clinical outcome confirmed the results of PCR, whether positive or negative. PCR results were available within 6.30 and 72 hours (mean: 18 hours).. This simple and rapid PCR technique can be applied in the daily routine of the microbiology laboratory. It allows early diagnosis of herpetic meningocephalitis or, when lacking, exclusion of Herpes simplex etiology.

Topics: Acyclovir; Antiviral Agents; Cerebrospinal Fluid; Child; Colorimetry; Cost-Benefit Analysis; DNA, Viral; Drug Costs; Encephalitis, Herpes Simplex; Humans; Polymerase Chain Reaction; Simplexvirus; Time Factors

Topics: Acyclovir; Aged; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Polymerase Chain Reaction; Time Factors

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Humans; Male

At 17th week of pregnancy, a 28-year-old woman was diagnosed as having herpes simplex encephalitis and treated with intravenous acyclovir. Follow-up by the serial ultrasound examinations, intrauterine growth retardation (IUGR) was found. During the course of disease, cordocentesis was performed to evaluate the risk of the disease and the infant's chromosomal constitution. No herpes simplex virus infection on cord blood sample was observed; however, chromosomal analysis revealed: 46,XX/47,XX,+2/47,XX,+11/47,XX,+19/48,XX,+11. After termination of pregnancy, the fetus was found as having ventricular septum defect. The presence of the triploid cell lines mocaicism involving chromosome 2 and 19 were confirmed by the analysis of fetal skin tissues. No attributable finding to herpes simplex virus infection and acyclovir treatment was found, and the presence of the triploid cell lines mocaicism were appeared to be purely coincidental.

Topics: Acyclovir; Adult; Chromosome Aberrations; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 19; Chromosomes, Human, Pair 2; Encephalitis, Herpes Simplex; Female; Humans; Mosaicism; Pregnancy; Prenatal Diagnosis; Trisomy

The outcome of herpes simplex virus (HSV) infections manifesting as encephalitis in healthy or immunocompromised individuals is generally very poor with mortality rates of about 8 to 28% with treatment. The long-term prognosis of survivors is often problematic, posing the need for alternative treatments that may decrease the mortality and morbidity associated with herpes encephalitis. This study addresses one such approach that includes a temporary permeabilization of the blood-brain barrier during treatment with acyclovir (ACV). In these studies we utilized a synthetic bradykinin analog, Cereport (RMP-7), in conjunction with ACV to treat HSV infection of the brain in a rat model. Cereport, infused intravenously via the jugular vein, was shown to increase [(14)C]ACV uptake in both the HSV-1-infected and -uninfected rat brain by approximately two- to threefold, correlating with enhanced efficacy of ACV in various brain compartments. In another series of experiments to determine efficacy, various doses of unlabeled ACV were administered during infusion with RMP-7. The decrease in viral titers in the temporal regions of the brain after 5 days of treatment suggested that this approach enhanced the efficacy of ACV treatment. These data indicated that Cereport infused with ACV enhances both the penetration and efficacy of this drug in the treatment of an experimental HSV-1 infection of the rat brain.

Topics: Acyclovir; Animals; Antiviral Agents; Biological Availability; Blood-Brain Barrier; Bradykinin; Brain; Capillary Permeability; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Infusions, Intravenous; Male; Rats; Rats, Inbred F344; Tissue Distribution

Herpes simplex virus (HSV) type I causes a fulminant necrotising meningoencephalitis distinguished from other encephalitides by its focal and often haemorrhagic nature. Specific antiviral therapy with acyclovir can significantly improve the prognosis. We present MRI findings of two cases of herpes simplex encephalitis (HSE) confirmed by PCR analysis, focusing on the serial changes after acyclovir therapy: gyral swelling, high signal intensity on T2-weighted images in the subfrontal region, temporal lobe and insula in the initial stage, then regional extension with enhancement and haemorrhage despite appropriate acyclovir therapy, and finally encephalomalacia and brain atrophy.

Topics: Acyclovir; Adolescent; Antiviral Agents; Brain; Child; DNA, Viral; Encephalitis, Herpes Simplex; Humans; Magnetic Resonance Imaging; Male; Polymerase Chain Reaction; Simplexvirus

A 54-year-old woman was admitted to the hospital suffering from fever and personality changes. Laboratory examination of her cerebrospinal fluid (CSF) showed 270 mononuclear cells, 30 polynuclear cells and a clinically low number of erythrocytes/mm3. Empirical clinical findings from this case suggested treatment with acyclovir. Magnetic resonance imaging (MRI) showed bilateral temporal hyperintense signals in T2-weighted images. PCR with specific primer for herpes simplex virus type 1 (HSV-1) and HSV-2 were negative. There was no elevation of oligoclonal antibodies specific to HSV in CSF after 2 weeks. Although we did not prove the presence of the agent microbiologically at the clinical onset of the disease, the MRI and electroencephalogram (EEG) findings, erythrocytes in CSF and the dramatic response to acyclovir therapy are suggestive of a diagnosis of herpes simplex encephalitis (HSE).

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; DNA, Viral; Encephalitis, Herpes Simplex; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Polymerase Chain Reaction; Simplexvirus; Treatment Outcome

Topics: Acyclovir; Aged; Antiviral Agents; Diagnosis, Differential; Encephalitis, Herpes Simplex; Encephalitis, Varicella Zoster; Female; Humans

Two infants with recurrence of herpes simplex virus (HSV) encephalitis are reported. Both patients developed HSV encephalitis during their neonatal period and were treated with iv acyclovir. Long-term oral acyclovir prophylaxis was given thereafter. At the age of 8 and 11 months respectively, both babies, while under oral acyclovir prophylaxis, presented a second episode of HSV encephalitis. An inadequate dose of suppressive oral acyclovir therapy may be responsible for the recurrence of encephalitis in these two babies.. The present observations emphasise the need for very long follow-up of any infant who has suffered from neonatal herpes simplex virus encephalitis and the need for careful prospective controlled studies in order to define the appropriate treatment regimen (initial plus prophylaxis) for neonates with herpes simplex virus infections.

Topics: Acyclovir; Antiviral Agents; Electroencephalography; Encephalitis; Encephalitis, Herpes Simplex; Female; Humans; Infant, Newborn; Injections, Intraperitoneal; Polymerase Chain Reaction; Recurrence; Simplexvirus; Time Factors

All patients admitted with provisional diagnosis of an encephalitic illness over a period of 30 months, were studied. Special investigations included CSF analysis, EEG, CT scan and MRI. Herpes simplex virus (HSV) antibody estimation in CSF and blood was done simultaneously using ELISA. Patients with diagnosis of cerebral venous thrombosis, cerebral malaria, tubercular meningitis etc, who resembled herpes simplex encephalitis (HSE), were excluded systematically with relevant investigations. 28 patients showed electroencephalographic, serologic and/or neuroradiological evidence of herpes simplex encephalitis. Males were affected more than females. Age ranged from 4 years to 65 years. Main clinical features included altered sensorium (100%) and seizures (89%). Serological test for HSV antibody in CSF and blood was positive in 14 patients. Fronto-temporal localisation was seen in EEG of 18 patients. CT and MRI were fairly characteristic with bilateral asymmetric fronto-temporal lesions. Patients with mild disease and who reported earlier responded well to treatment with acyclovir. Mortality was higher if treatment was delayed or if the disease was severe. Delayed treatment even in less severe cases produced neurological deficit in many survivors. Despite limitations of non-availability of CSF-PCR and serial estimation of HSV antibodies, the study is an attempt to highlight the value of high index of suspicion of HSE on clinical grounds, systematically excluding cases with different aetiologies resembling HSE and planning early antiviral therapy to reduce both mortality and morbidity associated with this fatal disease.

Topics: Acyclovir; Adolescent; Adult; Age Distribution; Antiviral Agents; Child; Child, Preschool; Encephalitis, Herpes Simplex; Female; Humans; India; Male; Middle Aged; Sex Distribution

Herpes simplex encephalitis (HSE) in children sometimes exacerbates after successful treatment; yet the frequency, etiology, and clinical features of exacerbation remain unclear. We report data for 27 children with HSE confirmed by polymerase chain reaction (PCR) analysis; all were successfully treated with acyclovir, but 7 (26%) had a relapse of encephalitic illness. In 2 of those 7, serial examination with a PCR assay showed that herpes simplex virus (HSV) DNA reappeared temporarily in the cerebrospinal fluid (CSF). For 5 of the 7 patients, a second course of acyclovir therapy was effective. Coxsackievirus A9 was isolated from CSF of 1 case patient during subsequent exacerbation. The total dose during initial acyclovir therapy was significantly lower in the relapse group than in the control group (P=.027). In conclusion, exacerbation of HSE in children may be more common than previously recognized. It is suggested that the replication of HSV or another viral pathogen caused a second encephalitic illness (HSE) in some cases.

Topics: Acyclovir; Adolescent; Antiviral Agents; Child, Preschool; DNA, Viral; Encephalitis, Herpes Simplex; Female; Humans; Infant; Male; Polymerase Chain Reaction; Recurrence; Simplexvirus

Neurological damage in Herpes simplex type 1 encephalitis results from neuronal cell death secondary to viral invasion, and from inflammatory changes and cerebral oedema secondary to the immune response to the virus. Corticosteroids could have an important role in the management of Herpes simplex encephalitis because their anti-inflammatory action reduces cerebral oedema. However their use has been limited by concerns that their immunosuppressive actions could increase viral replication and spread. The present study examined this issue in a rat model in which injection of HSV-1 into the cervical vagus nerve produced a well-defined focal encephalitis, characterised by an orderly progression of the virus through central neural pathways connected with vagal afferent termination sites in the medulla oblongata. After injection of HSV-1, rats were treated twice a day, either with vehicle (saline, 400 microl i.p.), with acyclovir (30 mg/kg i.p.), with dexamethasone (5 mg/kg i.p.), or with both acyclovir and dexamethasone. Animals were sacrificed after 72 h, and viral load in different brain regions was quantified by computer-assisted measurement of the area occupied by immunohistochemical reaction product. Treatment with acyclovir reduced viral load to 17 +/- 5% of the saline value (P < 0.01). After dexamethasone treatment, the viral load (63 +/- 13% of the saline value) was also reduced (P < 0.05). Treatment with both acyclovir and dexamethasone reduced viral load to 26 +/- 8% of the saline value (P < 0.01 compared with saline, and P > 0.05 compared to acyclovir alone). Our results confirm the effectiveness of acyclovir in a new model of HSV-1 infection, and provide evidence that corticosteroids do not inhibit the antiviral action of acyclovir. In addition corticosteroids may decrease the extent of infection in their own right. The acute time course studied in our model parallels the time course of acute Herpes simplex encephalitis in humans. Our data suggests that corticosteroids are not detrimental when combined with acyclovir in the management of this condition.

Topics: Acyclovir; Amygdala; Animals; Antigens, Viral; Dexamethasone; Disease Models, Animal; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Focal Infection; Herpesvirus 1, Human; Immunohistochemistry; Medulla Oblongata; Rats; Rats, Inbred F344; Vagus Nerve; Viral Load; Virus Replication

We report on a 12-year-old boy with herpes simplex encephalitis, in whom a severe localised skin reaction developed following the infusion of intravenous acyclovir. Oral valaciclovir was given as continuation therapy to complete the 3-week course of antiviral treatment and resulted in complete recovery without side effects. This report illustrates the advantage of using the polymerase chain reaction to diagnose herpes simplex encephalitis and the potential use of newer antiviral agents, such as valaciclovir, as continuation therapy in the management of the infection. The higher oral bioavailability of newer antiviral agents allows part of the extended treatment period of patients with herpes simplex encephalitis to be carried out as an ambulatory oral regimen.

Topics: Acyclovir; Antiviral Agents; Child; Encephalitis, Herpes Simplex; Humans; Male; Polymerase Chain Reaction; Prodrugs; Valacyclovir; Valine

To report a case of bullous eruption at and far from the site of aciclovir injection.. A 50-year-old man was treated with intravenous aciclovir for Herpes simplex meningoencephalitis. Ten days after treatment onset, blisters appeared on his right forearm, at and far from the site of aciclovir injection.. This adverse effect has not been frequently reported. To date, bullous eruptions were considered to result from extravasation of the aciclovir solution. In this case, an immunoallergic pattern was discussed with the presence of a histological leukocytoclastic vasculitis.

Topics: Acyclovir; Antiviral Agents; Blister; Drug Eruptions; Encephalitis, Herpes Simplex; Forearm; Humans; Injections, Intravenous; Male; Middle Aged; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Acyclovir; Adult; Brain; Child, Preschool; Encephalitis, Herpes Simplex; Epilepsy, Frontal Lobe; Female; Humans; Infant; Status Epilepticus

To investigate the diagnostic potential of herpes simplex virus (HSV) DNA in cerebrospinal fluid and serum; to correlate the findings with outcome in the child and with type of maternal infection.. Cerebrospinal fluid and serum specimens from 36 children with verified neonatal HSV infections, diagnosed between 1973 and 1996, were examined using the polymerase chain reaction technique (PCR).. In 21 children for whom both cerebrospinal fluid and sera were available, HSV DNA was found in one or both specimens in 19 (90%). Overall, HSV DNA was found in the cerebrospinal fluid of 74% of 27 children, and in the sera of 20 out of 30 children (67%). In two children HSV DNA was not demonstrable in either serum or cerebrospinal fluid. In sequential specimens from four children, the persistence of HSV DNA after the end of intravenous treatment was associated with a poor prognosis.. These findings indicate that HSV DNA detection in CSF and serum is highly sensitive for the diagnosis of neonatal HSV infections but does not replace the detection of virus in other locations using virus isolation and antigen detection.

Topics: Acyclovir; Antiviral Agents; DNA, Viral; Encephalitis, Herpes Simplex; Humans; Infant, Newborn; Infusions, Intravenous; Polymerase Chain Reaction; Simplexvirus

Herpes simplex encephalitis (HSE) rarely occurs in children, is not easily diagnosed, and has a poor prognosis.. We report a pediatric case with a relapse on the 29th day despite conventional acyclovir therapy. As the relapse mechanism is not clearly understood, antiviral and immunosuppressive therapy was administered.. This case underlines the importance of clinical examination and the necessity of accurate testing prior stopping antiviral treatment. A better understanding of the relapse mechanism is required in order to propose more efficient treatment.

Topics: Acyclovir; Anti-Anxiety Agents; Anti-Inflammatory Agents; Anticonvulsants; Antiviral Agents; Benzodiazepines; Brain; Child, Preschool; Clobazam; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Epilepsy; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Methylprednisolone Hemisuccinate; Recurrence; Time Factors; Tomography, X-Ray Computed; Valproic Acid; Vigabatrin

The efficacy of recombinant human interferon alpha B/D in experimental HSV-1 encephalitis was investigated in the murine system. Recombinant Hu-IFN-alpha B/D significantly reduced the mortality in a mouse encephalitis model (about 30%, P = 0.021), whereas natural mouse interferon was inactive. Combination of acyclovir with Hu-IFN-alpha B/D had an additive effect.

Topics: Acyclovir; Animals; Antiviral Agents; Disease Models, Animal; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Humans; Interferon Type I; Mice; Recombinant Proteins

We examined the serial MRI diffusion weighted images (DWIs) in two patients with acute viral encephalitis similar to herpes simplex encephalitis (HSE). Patient 1. A 27-year-old woman was admitted to the psychiatry ward for her confusional state and convulsions. Because of abnormal CSF findings she was transferred to the neurology ward, and the infusion of acyclovir was started. On disease day 5. MRI demonstrated high signal intensity in the left lateral lobe both on T2 weighted images (T2WIs) and DWIs. On day 18, MRI showed progression of the lesions, so acyclovir was changed to ara-A. On day 26, no improvement was seen clinically or radiologically. Then, combination therapy with acyclovir, ara-A and gamma-globulin was began. On day 36, she recovered completely, and abnormal intensity in MRI disappeared both on T2WIs and DWIs. Therefore, antiviral agent therapy was discontinued. Patient 2. A 31-year-old man was admitted for headache, fever and aphasia. On the next day, acyclovir was started and both DWIs and T2WIs of MRI demonstrated a high signal intensity in the left temporal lobe. Ten days later, he became perfectly well, and the increased signal intensity disappeared on DWIs, but not on T2WIs. Treatment was therefore discontinued. No relapse was in either patient. We concluded that serial MRI DWIs may be useful to determine when to discontinue the treatment in encephalitis.

Topics: Acyclovir; Adult; Antiviral Agents; Brain; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; gamma-Globulins; Humans; Image Enhancement; Magnetic Resonance Imaging; Male; Treatment Outcome; Vidarabine

We describe a patient who developed a severe but temporally limited retrograde amnesia coupled with a relatively mild anterograde amnesia following herpes simplex encephalitis. The patient showed a profound retrograde amnesia for autobiographical events extending for about 10 years prior to the disease onset. Her knowledge about public events and famous persons was also impaired for this period. An MRI and SPECT demonstrated bilateral medial temporal pathology. This case represents a further instance of a relatively focal retrograde amnesia following brain damage. We review other reported cases with focal retrograde amnesia and consider theoretical and neuroanatomical accounts for the present case. Two factors may account for her amnesic patterns: a partial disruption of the store for premorbid binding codes (i.e., information that multimodal feature representations occurred synchronously); along with a relative preservation of the encoding process required to develop new synchronous codes.

Topics: Acyclovir; Amnesia, Retrograde; Antibodies, Viral; Antiviral Agents; Electroencephalography; Encephalitis, Herpes Simplex; Epilepsy, Generalized; Female; Herpesvirus 1, Human; Hippocampus; Humans; Infusions, Intravenous; Lymphocytosis; Magnetic Resonance Imaging; Middle Aged; Neuropsychological Tests; Radiography; Severity of Illness Index; Temporal Lobe; Time Factors; Tomography, Emission-Computed, Single-Photon