acyclovir and Encephalitis

Infectious meningitis and encephalitis are associated with significant morbidity and mortality worldwide. Acute bacterial meningitis is rapidly fatal and early recognition and institution of therapy are imperative. Viral meningitis is typically a benign self-limited illness. Chronic meningitis (defined as presenting with >4 weeks of symptoms) is most often caused by tuberculosis and fungal infection. Because the diagnostic testing for tuberculous meningitis is insensitive and cultures often take weeks to grow, therapy is often initiated empirically when the diagnosis is suspected. Human simplex virus encephalitis is the most common cause of encephalitis and requires prompt treatment with intravenous acyclovir.

Topics: Acyclovir; Encephalitis; Humans; Meningitis, Bacterial; Meningitis, Viral

Topics: Acyclovir; Administration, Intravenous; Adult; Antiviral Agents; Encephalitis; Humans; Simplexvirus

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

We report a case of an acute HHV-7 encephalitis involving the nucleus of the VI cranial nerve in an immunocompetent host. The patient was an adult male admitted to our Clinic with headache, diplopia, fever, nausea, vertigo, asthenia and general malaise. PCR for viral and bacterial genomes was run on both serum and cerebral spinal fluid (CSF) after performing lumbar puncture, resulting positive only for HHV-7 DNA on CSF. MRI showed hyperintensity in FLAIR signal in the dorsal pons, in the area of the VI cranial nerve nucleus. Empirical therapy with Acyclovir and Dexamethasone was started at the time of admission and was continued after the microbiology results. After three days of therapy diplopia, fever and other previous clinical manifestations improved and the patient recovered normal sight. Our case report contributes to a better understanding of the presentation, diagnosis and treatment of HHV-7 encephalitis in immunocompetent patients due to reactivation in adult age.

Topics: Acyclovir; Adult; Anti-Inflammatory Agents; Antiviral Agents; Dexamethasone; Diagnosis, Differential; Encephalitis; Herpesvirus 7, Human; Humans; Immunocompetence; Male; Radiculopathy; Roseolovirus Infections; Treatment Outcome

Encephalitis is a serious and potentially treatable infection of the central nervous system. A pathogen is identified in less than 50% of cases. The differential diagnosis includes acute infection, immune-mediated causes, and other central nervous system processes. Emergent investigations include blood work, cerebrospinal fluid analysis, and neuroimaging. Empiric acyclovir and antibiotics should be started immediately to maximize the child's chance of neurologic recovery.

Topics: Acyclovir; Adolescent; Anti-Bacterial Agents; Antiviral Agents; Child; Diagnosis, Differential; Diagnostic Imaging; Encephalitis; Humans

Viral encephalitis causes an altered level of consciousness, which may be associated with fever, seizures, focal deficits, CSF pleocytosis, and abnormal neuroimaging. Potential pathogens include HSV, VZV, enterovirus, and in some regions, arboviruses. Autoimmune (eg, anti-NMDA receptor) and paraneoplastic encephalitis are responsible for some cases where no pathogen is identified. Indications for ICU admission include coma, status epilepticus and respiratory failure. Timely initiation of anti-viral therapy is crucial while relevant molecular and serological test results are being performed. Supportive care should be directed at the prevention and treatment of cerebral edema and other physiological derangements which may contribute to secondary neurological injury.

Topics: Acyclovir; Adrenal Cortex Hormones; Anticonvulsants; Antiviral Agents; Brain Diseases; Brain Edema; Consciousness Disorders; Encephalitis; Encephalitis, Viral; Encephalomyelitis, Acute Disseminated; Glasgow Coma Scale; Guillain-Barre Syndrome; Hashimoto Disease; Humans; Intensive Care Units; Paraneoplastic Syndromes, Nervous System; Seizures; Status Epilepticus; Viremia

Topics: Acyclovir; Adult; Antiviral Agents; Diagnosis, Differential; Diagnostic Imaging; Electroencephalography; Encephalitis; Herpes Simplex; Humans; Lymphocyte Count; Male; Polymerase Chain Reaction; Spinal Puncture

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

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

The Varicella zoster virus may affect the central nervous system (CNS) as a complication of herpes zoster (HZ). A series of neurological syndromes are described and, on the basis of a review of the literature and two illustrative case histories, the symptomatology, pathogenesis, therapeutic possibilities and the diagnostic difficulties in HZ-associated cerebral vasculitis and HZ-associated encephalitis are reviewed. Progressive multifocal encephalopathy in immune-insufficient individuals is briefly mentioned. The diagnosis is most frequently established on the basis of the clinical picture when the characteristic symptoms develop in connection with cutaneous HZ. A long latent period may result in defective recognition of the connection. Immuno-suppression and dissemination are critical determinants for the course of the condition but, in immune-competent individuals, the morbidity and mortality are low. Treatment with acyclovir is employed to an increasing extent with good results but the conditions are rare and clinically controlled investigations are not available. It is important that the possibility of HZ-associated CNS-disease is borne in mind, in view of the therapeutic possibilities. The pathogeneses of these complications is little understood but there is increasing evidence that a direct viral invasion is the mechanism responsible. A post-infectious immune-mediate mechanism is also another popular opinion.

Topics: Acyclovir; Adult; Diagnosis, Differential; Encephalitis; Encephalomyelitis; Female; Herpes Zoster; Humans; Male; Middle Aged; Prognosis; Vasculitis

Herpes simplex encephalitis (HSE) is the most common nonepidemic cause of acute viral encephalitis. Since successful therapy depends on a high level of suspicion that HSE is present and on the early administration of antiviral treatment, knowledge of clinical and laboratory findings of HSE is of great importance. The clinical hallmark of HSE are signs of both focal and diffuse neurologic involvement. Our case report exemplifies the diagnostic problems that can occur in HSE-patients. The validity of the different ancillary examinations is discussed. Up to the present time brain biopsy has been the method of choice for a reliable early diagnosis of HSE. In the foreseeable future early diagnosis is likely to become available in a non-invasive way by the polymerase-chain reaction. Immediate antiviral therapy with acyclovir in HSE has proved to be useful in rigorously controlled trials. The clinical picture of the acyclovir-induced encephalopathy represents a disorder that can be probably avoided by means of a sufficient hydration.

Topics: Acyclovir; Adult; Antigens, Viral; Encephalitis; Female; Herpes Simplex; Humans; Immunologic Techniques; Simplexvirus; Tomography, X-Ray Computed

Neonatal herpes simplex virus (HSV) infections are of increasing incidence in North America, now occurring at a rate of approximately one in 3,500 to one in 5,000 deliveries per year. Disease manifests as one of three forms; namely, infection: localized to the skin, eye and mouth (SEM), encephalitis (CNS), or disseminated disease. With the advent of antiviral therapy, it has become possible to decrease mortality and improve morbidity for babies suffering from infection. Advances in antiviral therapy have allowed for prevention of disease progression beyond states of SEM involvement. Furthermore, life threatening infections of the CNS or of multiple organs, have mortality with either acyclovir or vidarabine therapy. Now approximately 15% (CNS) and 50% (disseminated disease) of babies die from neonatal HSV disease. The results of ongoing studies in the United States will summarize the pathogenesis and treatment of neonatal HSV infection.

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Female; Herpes Simplex; Humans; Infant, Newborn; Nervous System Diseases; Pregnancy; Simplexvirus; Vidarabine

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans; Polymerase Chain Reaction; Treatment Outcome; Vidarabine

Patients with Herpes simplex encephalitis often are considered to be poor rehabilitation candidates because of their multiple deficits and grave prognosis. This report presents case reports on three patients with biopsy-proven Herpes simplex encephalitis, all of whom were treated with acyclovir in acute care and then admitted to an inpatient rehabilitation program. All had multiple brain lesions with minimal motor findings but cognitive and communication deficits. One patient, two weeks after admission, slipped into a coma and was transferred to an acute care hospital where he subsequently expired. The other two made useful functional gains and were discharged home in two weeks and 10 weeks, suggesting that a trial of rehabilitation may be warranted after Herpes simplex encephalitis.

Topics: Activities of Daily Living; Acute Disease; Acyclovir; Adaptation, Physiological; Adult; Encephalitis; Female; Herpes Simplex; Humans; Male; Middle Aged; Prognosis

Aciclovir (ACV) is the most effective drug for the virostatic management of herpes simplex virus (HSV) infections, and the rate of side-effects is low. ACV resistance is rare, occurring only in highly immunocompromised patients (so far about 30 cases have been reported). Dosages and modes of application of ACV in different HSV infections are indicated and discussed.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Microbial; Eczema; Encephalitis; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Humans

CMV disease is a major problem in AIDS, though with a different profile from that seen in other immunosuppressed patients. The novel treatments, ganciclovir and phosphonoformate, have a major role in the management of such infections, but maintenance therapy is often required. Optimal maintenance regimens have yet to be established, especially where zidovudine is also being used.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Addison Disease; Antiviral Agents; Colitis; Cytomegalovirus Infections; Encephalitis; Esophageal Diseases; Foscarnet; Ganciclovir; Humans; Phosphonoacetic Acid; Pneumonia, Viral; Retinitis

Acute viral and other infectious causes of encephalitis usually produce fever, headache, stiff neck and alterations in consciousness, focal neurologic signs and seizures. A large number of viral and nonviral agents can cause encephalitis. Arthropod-borne viruses peak in summer, the tick-borne infections occur in early summer, enterovirus infections in later summer and mumps in the winter and spring.

Topics: Acyclovir; Encephalitis; Encephalitis, Tick-Borne; Enterovirus Infections; Herpes Simplex; Humans; Mumps; Seasons

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Brain Edema; Bromodeoxyuridine; Dexamethasone; Drug Therapy, Combination; Encephalitis; Ganciclovir; Herpes Simplex; Humans; Immunoglobulins; Interferons; Vidarabine

Topics: Acyclovir; Child; Encephalitis; Female; Herpesviridae Infections; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Herpes simplex virus (HSV) infections of the central nervous system are a significant cause of mortality and morbidity. The introduction of antiviral therapy has improved the outcome for patients with life-threatening disease. Neonatal HSV infection is usually acquired at the time of delivery by contact of the fetus with infected maternal genital secretions resulting in disease that can be localized to the skin, eye, and mouth, and can lead to encephalitis or become disseminated. A total of 291 babies with neonatal HSV infection have been evaluated over a period of 14 years with mortality and morbidity rates determined at one year. Vidarabine therapy decreased the incidence of mortality and improved morbidity rates; however, further improvement in mortality rates with acyclovir therapy has not been apparent. No significant clinical toxicity appeared in either treatment group. In order to improve outcome, earlier intervention and prophylactic strategies must be developed. For patients with herpes simplex encephalitis, acyclovir therapy is superior to vidarabine therapy for biopsy-proven disease. When outcome is compared for 136 vidarabine- and 46 acyclovir-treated, biopsy-proven patients, mortality rates are decreased to 20 percent with acyclovir, and approximately 40 percent of survivors are evaluated as normal at one year after therapy. Despite better outcome with antiviral therapy for the treatment of biopsy-proven herpes simplex encephalitis, further improvement is required.

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Herpes Simplex; Humans; Infant; Infant, Newborn; Vidarabine

Topics: Acyclovir; Adult; Anti-Bacterial Agents; Bacterial Infections; Encephalitis; Humans; Meningitis; Meningitis, Viral

Topics: Acyclovir; Aphasia; Drug Administration Schedule; Encephalitis; Herpes Simplex; Humans; Immune Tolerance; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Recurrence

Herpes simplex encephalitis is a rapidly progressive disease in neonates and adults. Mortality is high, and there are severe neurologic sequelae in survivors. The reasons for centripetal transfer of virus to the brain are not fully understood. Prompt diagnosis followed by antiviral therapy with acyclovir significantly improves the prognosis. Controversy surrounds the need for brain biopsy before antiviral therapy is started.

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans

Herpes simplex encephalitis (HSE) is an uncommon disease, yet 25 to 30 per cent of cases involve children. The initial clinical findings are nonspecific (fever, altered mental status), but most cases evolve to demonstrate focal neurologic signs and symptoms. The CSF is abnormal in over 90 per cent of cases. The EEG, CT, and MRI will further help in detecting focal encephalitis. The clinician caring for a child with focal encephalitis should institute broad-spectrum antimicrobial therapy plus acyclovir, pending definitive diagnosis by ancillary tests or brain biopsy, which is positive for HSE 33 to 55 per cent of the time and is diagnostic for other treatable conditions 10 to 20 per cent of the time. Acyclovir is the drug of choice for HSE and substantially reduces mortality and morbidity. The management of HSE in a child requires an experienced team of specialists and laboratory support in a tertiary intensive care setting.

Topics: Acyclovir; Child; Encephalitis; Herpes Simplex; Humans; Vidarabine

Topics: Acyclovir; Autonomic Nervous System Diseases; Encephalitis; Esophagitis; Facial Dermatoses; Female; Fingers; Hepatitis, Viral, Human; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Humans; Infant, Newborn; Keratitis, Dendritic; Male; Peripheral Nervous System Diseases; Recurrence; Respiratory Tract Infections; Stomatitis, Herpetic; Vaccination; Viral Vaccines

Topics: Acyclovir; Adult; Antiviral Agents; Chickenpox; Clinical Trials as Topic; Encephalitis; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Idoxuridine; Infant, Newborn; Infant, Newborn, Diseases; Keratitis, Dendritic; Trifluridine; Vidarabine

Acyclovir is now established as an effective and well tolerated therapeutic agent for the management of at least the more common infections of the herpes virus group. Evaluation of the drug nevertheless continues, primarily to verify its value in those infections caused by cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Furthermore with the development of analogues of acyclovir with better absorption profiles or enhanced anti-viral activity the future for this area of anti-viral therapy looks optimistic.

Topics: Acyclovir; Cytomegalovirus Infections; Encephalitis; Forecasting; Hepatitis B; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Humans; Immune Tolerance; Infectious Mononucleosis; Keratitis, Dendritic; Recurrence

Topics: Acyclovir; Administration, Oral; Administration, Topical; Antiviral Agents; Child; Encephalitis; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Humans; Idoxuridine; Infant, Newborn; Male; Pregnancy; Stomatitis, Herpetic; Vidarabine

Topics: Acyclovir; Antiviral Agents; Chickenpox; Clinical Trials as Topic; Encephalitis; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Idoxuridine; Infant, Newborn; Keratitis, Dendritic; Keratoconjunctivitis; Male; Vidarabine

Infections with herpes simplex virus (HSV) are extremely common. HSV infection may be asymptomatic or may cause any one of a wide variety of disease syndromes. In this review, the physical properties and mode of replication of HSV are briefly described, and an outline of the different clinical manifestations associated with HSV infection is presented. Principles of diagnosis, treatment, and prevention of these infections are also discussed.

Topics: Acyclovir; Adult; Animals; Child; Encephalitis; Female; Genes, Viral; Herpes Genitalis; Herpes Simplex; Humans; Infant, Newborn; Male; Meningitis, Viral; Pregnancy; Recurrence; Simplexvirus; Stomatitis, Herpetic; Transcription, Genetic; Vidarabine; Virus Replication

The recent profusion of antiviral research has resulted in significant advances toward prevention and treatment of herpes group virus infections. The most promising new agent is acyclovir, which is available in topical, intravenous, and oral formulations. Results of clinical trials of acyclovir for prevention and treatment of herpes simplex, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus infections are discussed, and the potential problem of antiviral resistance considered. Vidarabine therapy is reviewed briefly, and future new drugs with activity against herpesviruses are mentioned.

Topics: Acyclovir; Chickenpox; Cytomegalovirus Infections; Drug Resistance, Microbial; Encephalitis; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Keratitis, Dendritic; Male; Vidarabine

Topics: Acyclovir; Administration, Topical; Adolescent; Amantadine; Antiviral Agents; Chickenpox; Child; Clinical Trials as Topic; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Idoxuridine; Influenza, Human; Keratitis, Dendritic; Male; Rimantadine; Vidarabine

The patient with meningoencephalitis should be evaluated carefully for the presence of focal signs referable to involvement of the frontotemporal regions of the brain. A significant percentage of cases of encephalitis with discrete focal features are caused by infection with herpes simplex virus. If focal signs are not present, the patient should be managed conservatively but examined regularly because focal neurologic dysfunction may present at any time in the course of disease. If there is clinical and electrographic evidence of involvement of the frontotemporal lobes, radiographic imaging is indicated as well as studies of the serum and cerebrospinal fluid for antibodies indicative of a recent infection with herpes simplex virus. Assuming that the radiographic scans identify the characteristic changes of a focal encephalitis and that the antibody responses are indicative of a recent herpes simplex virus infection, brain biopsy should be done in order to confirm the diagnosis. With positive evidence for HSE, treatment with ara-A should be initiated and continued for 10 days. If the biopsy proves negative for virus, ara-A should be discontinued and the patient managed conservatively (Fig. 3). Although the NIAID study of ara-A treatment of HSE is encouraging, the numbers are small and the evidence is, at best, only suggestive. It is reasonable to use this drug until a better one becomes available for the treatment of known HSE, and treatment should be instituted early before cellular injury is extensive. In centers familiar with this problem, biopsy confirmation of the diagnosis is a simple and informative procedure and can be defended. If patients cannot be moved to a center of this type, physicians familiar with the many facets of this problem should be consulted, and a decision regarding biopsy and treatment should be individualized in light of the circumstances. Biopsy should only be undertaken when the procedure can be done with minimal risk to the patient and the assurance that the maximum amount of information can be gained.

Topics: Acyclovir; Antibodies, Viral; Biopsy; Combined Modality Therapy; Electroencephalography; Encephalitis; Herpes Simplex; Humans; Pseudotumor Cerebri; Seizures; Simplexvirus; Tomography, Emission-Computed; Tomography, X-Ray Computed; Vidarabine; Vidarabine Phosphate

Guidelines for the prophylaxis or therapy of herpesvirus infections are shown in Table 1. Progress is so rapid in this area that frequent revisions of such guidelines will be necessary. Newer drugs or new formulations of older agents are constantly being developed. Combination therapies--e.g., interferon plus acyclovir--appear promising in laboratory models of herpesvirus infections and will undoubtedly receive clinical investigation in the years ahead. The problem of dealing with latent virus infections still eludes us, and major breakthroughs will be necessary before we can discuss cure of recurrent infections. Nevertheless, important strides have been made in the past few years, and further progress is predictable in the years ahead.

Topics: Acyclovir; Clinical Trials as Topic; Cytomegalovirus Infections; Encephalitis; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpesviridae Infections; Humans; Immune Tolerance; Infant, Newborn; Interferon Type I; Keratitis, Dendritic; Male; Vidarabine

In vitro sensitivity data suggest that acyclovir should be effective against clinical manifestations of herpes simplex virus types 1 and 2, varicella-zoster virus and possibly Epstein-Barr virus. The clinical potential against herpes simplex virus types 1 and 2 is further supported by results in animal models. Human cytomegalovirus and the veterinary herpes viruses, with the possible exception of equine herpes virus type 1, may be insufficiently sensitive to be amenable to treatment.

Topics: Acyclovir; Animals; Cytomegalovirus; Encephalitis; Guinea Pigs; Hepatitis B virus; Herpes Simplex; Herpesvirus 1, Cercopithecine; Herpesvirus 3, Human; Herpesvirus 4, Human; Humans; In Vitro Techniques; Keratitis, Dendritic; Mice; Rabbits; Recurrence; Simplexvirus

Acyclovir (aciclovir) is a nucleoside analogue antiviral drug related to cytarabine, idoxuridine, trifluridine and vidarabine. In common with these earlier antivirals, acyclovir is active against some members of the herpesvirus group of DNA viruses. The efficacy of topical acyclovir has been convincingly demonstrated in ocular herpetic keratitis, and in initial and primary initial genital herpes infection, but little or no clinical benefit was seen when non-primary initial genital infections were assessed separately. Acyclovir ointment demonstrated little benefit in recurrent genital herpes but topical acyclovir cream decreased the course of the infection by 1 to 2 days. Orally and intravenously administered acyclovir were beneficial in initial genital herpes infections, and oral therapy shortened the duration of recurrent infections by 1 to 2 days but did not ameliorate pain. In non-immunocompromised patients with recurrent herpes simplex labialis, generally little clinical benefit was seen with the use of topical acyclovir ointment even when therapy was initiated during the prodromal phase, while topical acyclovir cream effected small but significant improvements in the clinical but not the symptomological course of the disease. However, in immunocompromised patients, both intravenous and topical acyclovir shortened the clinical course of herpes simplex virus infections occurring mainly on the lips, oral mucosa and face, and prophylaxis with either oral or intravenous acyclovir suppressed the appearance of recurrent lesions from latent virus for the period of drug administration, but acyclovir did not eradicate latent herpesviruses. In non-immunocompromised patients, intravenous acyclovir was shown to decrease the acute pain of zoster, especially in the elderly, but postherpetic neuralgia was not ameliorated. When immunocompromised patients were studied, intravenous acyclovir inhibited the progression of zoster infections and shortened the healing time and duration of viral shedding in patients with cutaneous disseminated zoster. However, acute and post-herpetic pain were not significantly affected. Well designed controlled studies are underway to establish the efficacy of acyclovir in herpes simplex encephalitis and cytomegalovirus infections in immunocompromised patients, infections due to Epstein-Barr virus, and neonatal herpesvirus infections. Despite some aspects of the drug's use which require further clarification, acyclovir will make a major imp

Topics: Acyclovir; Animals; Clinical Trials as Topic; Cytomegalovirus; Drug Resistance, Microbial; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Herpesvirus 4, Human; Humans; Immunity; Keratitis, Dendritic; Kinetics; Male; Mutagens; Recurrence

The chief characters of infection by the human herpes viruses are considered with particular reference to herpes simplex viruses, types 1 and 2. Infection with type 1 virus is acquired very early in life though infrequently as a true congenital transmission of virus. Primary infections result from direct contact usually with infected saliva or skin vesicles. Kerato-conjunctivitis, when primary, may be severe yet superficial in extent. Vulvo-vaginitis, often acquired in adults as a result of type 2 infection by sexual transmission, can give extensive but superficial ulceration and discharge. Recurrent infections located on the dermatome with the same nerve supply as that of the organ affected primarily occur throughout life and at relatively short intervals. Sensory nerve ganglia harbour the virus particles as latent infection and when reactivation occurs virus spreads along nerve fibres to the skin. The most serious infections occur as disseminated disease with liver involvement in the neonatal period, in infants suffering from malnutrition or those undergoing immunosuppression for malignancies. Eczematous children are then at particular risk from spreading haemorrhagic skin lesions (Kaposi's eruption). Herpes encephalitis, commoner in adults than children, is an insidious severe disease with mortality related to the depth of coma. Antiviral therapy though successful may lead to chronic neurological sequelae. The success of antiviral therapy in herpes partly turns on the ability to bring the drug into close contact with the infected tissues. Latent virus is relatively unaffected by acyclovir and thus far recurrences have continued to occur.

Topics: Acyclovir; Adult; Antibodies, Viral; Encephalitis; Herpes Labialis; Herpes Simplex; Humans; Infant, Newborn; Keratitis, Dendritic; Recurrence; Time Factors

Herpes simplex encephalitis and neonatal herpes simplex virus infections are important consequences of herpes simplex virus infections of humans. The association of both diseases with significant mortality and morbidity has prompted intensive therapeutic trials designed to improve outcome. The NIAID Collaborative Antiviral Study Group has been able to demonstrate that vidarabine therapy decreases the mortality and improves morbidity for both herpes simplex encephalitis and neonatal herpes simplex virus infections. Nevertheless, mortality for both diseases is about 40% and many survivors are left with significant neurological impairment. With the hope of improving outcome, we initiated comparative trials of vidarabine and acyclovir for these two diseases. This report summarizes the status of these trials, which are still underway, with particular reference to the complexities of studies such as these. Because adequate numbers of patients for definitive statistical analyses have not been entered into the trial, data were assessed according to outcome for the entire group, irrespective of drug administered. The mortality of herpes simplex encephalitis and neonatal herpes simplex virus infections has been reduced to 34 and 30%, respectively, a decrease of approximately 10% for each disease. Further analyses await completion of the trials.

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Random Allocation; Time Factors; Vidarabine

Autoimmune encephalitis is a new spectrum of autoimmune disorders of the central nervous system (CNS), which are characterized by pathogenic autoantibodies against neuronal surface antigens. Clinical presentations range from acute to subacute encephalopathy with neurological and psychiatric symptoms, and life-threatening autonomic dysfunction in severe cases. There exist no approved therapies nor is data available from controlled clinical trials. Patients are usually treated with diverse combinations of immunotherapy. However, effect of immunotherapy on antibody-producing cells and thus on levels of pathogenic autoantibodies is insufficient. Therefore, therapeutic response is sometimes prolonged with necessity of long-time intensive care treatment and also irreversible deficits occur in severe cases. This trial will investigate the efficacy and safety of bortezomib, a proteasome inhibitor known to selectively deplete plasma cells, in patients with severe autoimmune encephalitis who have been treated with rituximab with insufficient response.. Generate-Boost is an investigator-initiated, multicenter, double-blinded, randomized controlled phase II trial which will be conducted in specialized neurological hospitals within the GENERATE (GErman NEtwork for Research on AuToimmune Encephalitis) network in Germany. Adult patients with severe autoimmune encephalitis (modified Rankin scale, mRS ≥ 3), autoantibodies against neuronal surface antigens, and pretreatment with rituximab are eligible for study participation. Fifty patients will be randomized 1:1 and undergo up to 3 cycles (each 21 days with 4 s. c. applications) of bortezomib or placebo. All patients will receive concomitant medication with dexamethasone, acyclovir and co-trimoxazole. The primary efficacy endpoint is the mRS score 17 weeks after first treatment application. Secondary endpoints are neurocognitive function, antibody titers, markers of neuronal cell damage, length of ICU/hospital stay, and mRS and Glasgow coma scale scores throughout the trial up to week 17. General and bortezomib-specific adverse events are monitored continuously.. The expected outcome of the study is to obtain first reliable data on a hypothesis-driven therapeutic option in severe and difficult-to-treat autoimmune encephalitis. If treatment with bortezomib is beneficial in these cases, this will be the basis for implementation in the current guidelines.. Clinicaltrials.gov , NCT03993262 . Registered June 20, 2019; German Clinical Trials Register, DRKS00017497.

Topics: Acyclovir; Adult; Autoantibodies; Bortezomib; Clinical Trials, Phase II as Topic; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Encephalitis; Germany; Glasgow Coma Scale; Hashimoto Disease; Humans; Immunotherapy; Multicenter Studies as Topic; Prospective Studies; Proteasome Inhibitors; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To determine whether a tailored multifaceted implementation strategy improves the initial management of patients with suspected encephalitis.. Pragmatic two arm cluster randomised controlled trial.. Hospitals within the United Kingdom.. Twenty-four hospitals nested within 12 postgraduate deaneries. Patients were identified retrospectively by searching discharge, microbiology, radiology and pharmacy records and included if they met clinical criteria or had a recorded suspicion of encephalitis.. An implementation strategy designed to overcome barriers to change, comprising local action planning, education and training, feedback on performance, a lumbar puncture pack and a range of optional components.. The primary outcome was the proportion of patients with suspected encephalitis undergoing diagnostic lumbar puncture within 12 hours of admission and starting aciclovir treatment within six hours. Secondary outcomes included the proportions of adults and children who had a lumbar puncture, who had appropriate cerebrospinal fluid investigations, and who had appropriate radiological imaging within 24 hours of admission. Data were collected from patient records for 12 months before and 12 months during the intervention period, and analysed blind to allocation.. 13 hospitals were randomised to intervention and 11 to control (no intervention), with 266 and 223 patients with suspected encephalitis identified respectively. There was no significant difference in primary outcome between intervention and control hospitals (13.5% and 14.8% respectively, p = 0.619; treatment effect -0.188, 95% confidence interval -0.927 to 0.552), but both had improved compared to pre-intervention (8.5%).. The improvement in both intervention and control arms may reflect overall progress in management of encephalitis through wider awareness and education.. Controlled Trials: ISRCTN06886935.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Encephalitis; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Spinal Puncture; United Kingdom

Neonatal herpes simplex virus (HSV) infections are of increasing incidence in North America, now occurring at a rate of approximately one in 3,500 to one in 5,000 deliveries per year. Disease manifests as one of three forms; namely, infection: localized to the skin, eye and mouth (SEM), encephalitis (CNS), or disseminated disease. With the advent of antiviral therapy, it has become possible to decrease mortality and improve morbidity for babies suffering from infection. Advances in antiviral therapy have allowed for prevention of disease progression beyond states of SEM involvement. Furthermore, life threatening infections of the CNS or of multiple organs, have mortality with either acyclovir or vidarabine therapy. Now approximately 15% (CNS) and 50% (disseminated disease) of babies die from neonatal HSV disease. The results of ongoing studies in the United States will summarize the pathogenesis and treatment of neonatal HSV infection.

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Female; Herpes Simplex; Humans; Infant, Newborn; Nervous System Diseases; Pregnancy; Simplexvirus; Vidarabine

Using the decision analysis technique and multivariate regression methods, a statistical model was established to define the utility of brain biopsy for diagnostic evaluation of patients with suspected herpes simplex encephalitis (HSE). Two strategies were compared: strategy I, brain biopsy with acyclovir (ACV) treatment for 10 days in biopsy-positive patients, and strategy II, ACV therapy without brain biopsy. Strategy I resulted in a greater 6-month survival rate when the likelihood of patients having HSE was less than 70%. Based on the current estimated prevalence of HSE (for patients with suspected HSE) of 35%, strategy I showed a slight advantage of a 3.2% increase in 6-month survival rate. An individual patient's chance of a positive brain biopsy can be predicted using a mathematical equation based on several important clinical assessments. This equation in conjunction with the decision analysis is a useful guide for the clinical management of patients with regard to brain biopsy.

Topics: Acyclovir; Biopsy; Brain; Encephalitis; Herpes Simplex; Humans; Models, Statistical; Multivariate Analysis; Prevalence; Probability; Regression Analysis

Despite the use of vidarabine, herpes simplex virus (HSV) infection in neonates continues to be a disease of high morbidity and mortality. We undertook a controlled trial comparing vidarabine with acyclovir for the treatment of neonatal HSV infection.. Babies less than one month of age with virologically confirmed HSV infection were randomly and blindly assigned to receive either intravenous vidarabine (30 mg per kilogram of body weight per day; n = 95) or acyclovir (30 mg per kilogram per day; n = 107) for 10 days. Actuarial rates of mortality and morbidity among the survivors after one year were compared overall and according to the extent of the disease at entry into the study (infection confined to the skin, eyes, or mouth; encephalitis; or disseminated disease).. After adjustment for differences between groups in the extent of disease, there was no difference between vidarabine and acyclovir in either morbidity (P = 0.83) or mortality (P = 0.27). None of the 85 babies with disease confined to the skin, eyes, or mouth died. Of the 31 babies in this group who were treated with vidarabine and followed for a year, 88 percent (22 of 25) were judged to be developing normally after one year, as compared with 98 percent (45 of 46) of the 54 treated with acyclovir (95 percent confidence interval for the difference, -4 to 24). For the 71 babies with encephalitis, mortality was 14 percent with vidarabine (5 of 36) and with acyclovir (5 of 35); of the survivors, 43 percent (13 of 30) and 29 percent (8 of 28), respectively, were developing normally after one year (95 percent confidence interval for the difference, -11 to 39). For the 46 babies with disseminated disease, mortality was 50 percent (14 of 28) with vidarabine and 61 percent (11 of 18) with acyclovir (95 percent confidence interval for the difference, -20 to 40); of the survivors, 58 percent (7 of 12) and 60 percent (3 of 5), respectively, were judged to be developing normally after one year (95 percent confidence interval for the difference, -40 to 50). Both medications were without serious toxic effects.. In this multicenter, randomized, blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal HSV infection. The study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized HSV, encephalitis, or disseminated disease.

Topics: Acyclovir; Encephalitis; Female; Herpes Simplex; Humans; Infant, Newborn; Injections, Intravenous; Male; Recurrence; Vidarabine

Herpes simplex virus (HSV) infections of the central nervous system are a significant cause of mortality and morbidity. The introduction of antiviral therapy has improved the outcome for patients with life-threatening disease. Neonatal HSV infection is usually acquired at the time of delivery by contact of the fetus with infected maternal genital secretions resulting in disease that can be localized to the skin, eye, and mouth, and can lead to encephalitis or become disseminated. A total of 291 babies with neonatal HSV infection have been evaluated over a period of 14 years with mortality and morbidity rates determined at one year. Vidarabine therapy decreased the incidence of mortality and improved morbidity rates; however, further improvement in mortality rates with acyclovir therapy has not been apparent. No significant clinical toxicity appeared in either treatment group. In order to improve outcome, earlier intervention and prophylactic strategies must be developed. For patients with herpes simplex encephalitis, acyclovir therapy is superior to vidarabine therapy for biopsy-proven disease. When outcome is compared for 136 vidarabine- and 46 acyclovir-treated, biopsy-proven patients, mortality rates are decreased to 20 percent with acyclovir, and approximately 40 percent of survivors are evaluated as normal at one year after therapy. Despite better outcome with antiviral therapy for the treatment of biopsy-proven herpes simplex encephalitis, further improvement is required.

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Herpes Simplex; Humans; Infant; Infant, Newborn; Vidarabine

A total of 208 patients underwent brain biopsy for presumptive herpes simplex encephalitis and were randomized to receive either vidarabine, vira-A, at 15 mg/kg/day, or acyclovir, at 30 mg/kg/day for ten days. 69 patients (33%) had biopsy-proven disease; 37 received vira-A and 32 acyclovir. With the exception of age, patient populations were balanced for demographic characteristics. Overall survival for acyclovir recipients was 72% compared with 46% for vira-A-treated patients 18 months after therapy (p = 0.008). After adjustment for differences of age between treatment populations by multivariant regression analyses, acyclovir treatment remained superior to vidarabine therapy (p = 0.041). Mortality varied according to the level of consciousness at the onset of therapy. For lethargic, semicomatose and comatose patients, mortality was 42%, 46%, and 67%, respectively, for the vira-A-treated patients and 0%, 25% and 25%, respectively, for acyclovir-treated patients. Six months post-therapy morbidity assessments revealed five (14%) vira-A versus 12 (38%) acyclovir recipients who had returned to normal function, while eight (22%) and three (9%), respectively, had moderate debility. Outcome differences were significant (p = 0.02; Wilcoxon, 2-sample test) using an adapted scoring system. Age and Glasgow coma scale greater than 10 predicted the best outcome following acyclovir treatment. Disoriented patients who flex and respond by eye to pain had no mortality and 50% returned to normal. These data indicate that acyclovir is the treatment of choice for biopsy-proven herpes simplex encephalitis.

Topics: Acyclovir; Adult; Clinical Trials as Topic; Encephalitis; Herpes Simplex; Humans; Middle Aged; Random Allocation; Regression Analysis; Vidarabine

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Female; Herpes Simplex; Humans; Seizures; Vidarabine

We randomly assigned 208 patients who underwent brain biopsy for presumptive herpes simplex encephalitis to receive either vidarabine (15 mg per kilogram of body weight per day) or acyclovir (30 mg per kilogram per day) for 10 days. Sixty-nine patients (33 percent) had biopsy-proved disease; 37 received vidarabine, and 32 acyclovir. The mortality in the vidarabine recipients was 54 percent, as compared with 28 percent in the acyclovir recipients (P = 0.008). Six-month mortality varied according to the Glasgow coma score at the onset of therapy. For scores of greater than 10, 7 to 10, and less than or equal to 6, mortality was 42, 46, and 67 percent in the patients treated with vidarabine, as compared with 0, 25, and 25 percent in those treated with acyclovir. A six-month morbidity assessment using an adapted scoring system revealed that 5 of 37 patients receiving vidarabine (14 percent) as compared with 12 of 32 receiving acyclovir (38 percent) were functioning normally (P = 0.021). Eight vidarabine-treated patients (22 percent) and three acyclovir-treated patients (9 percent) had moderate debility. Patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acyclovir treatment. We conclude that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis.

Topics: Acyclovir; Adolescent; Adult; Biopsy; Brain; Child; Child, Preschool; Encephalitis; Female; Herpes Simplex; Humans; Infant; Male; Middle Aged; Random Allocation; Simplexvirus; Vidarabine

After a discussion of the principles of antiviral chemotherapy, treatment and chemoprophylaxis of the following virus infections are reviewed in detail: the various manifestations of herpes simplex virus infections, varicella-zoster, cytomegalovirus infections, Epstein-Barr virus infections, laryngeal papillomas, and influenza A. Special reference is made to the treatment of immunocompromized patients. Acycloguanosine (acyclovir) has been found particularly useful in the treatment of herpes simplex virus and varicella zoster virus infections in immunocompromized patients and for herpesencephalitis. Varicella-zoster can also be treated effectively with bromovinyldeoxyuridine (BVDU). Toxicity of the currently used antiviral drugs is discussed as well as the problem of drug resistance.

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Child; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Immunologic Deficiency Syndromes; Infant, Newborn; Pemphigoid Gestationis; Pregnancy; Vidarabine; Virus Diseases

Antiviral compounds have been developed for use in chemoprophylaxis and chemotherapy of a variety of infections in humans, including those caused by influenza viruses, respiratory syncytial virus, and herpesviruses. The efficacy of several of these compounds has been demonstrated in rigorously controlled trials. Advances in molecular virology have led to the identification of biochemically defined, virus-specific functions that serve as appropriate targets for the future development of antiviral compounds. Clinical investigators and practicing physicians are now confronting questions previously raised with the use of antibacterial antibiotics. These questions concern appropriate routes of administration for antiviral compounds, optimal dosage regimens, risks of long-term prophylaxis, and the emergence of resistant organisms.

Topics: Acyclovir; Adult; Aged; Amantadine; Antiviral Agents; Chickenpox; Clinical Trials as Topic; Cytomegalovirus; Encephalitis; Foscarnet; Guanosine Triphosphate; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Influenza A virus; Influenza, Human; Phosphonoacetic Acid; Respiratory Tract Infections; Ribavirin; Rimantadine; Vidarabine; Virus Diseases

Topics: Acyclovir; Adult; Antiviral Agents; Chickenpox; Clinical Trials as Topic; Encephalitis; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Idoxuridine; Infant, Newborn; Infant, Newborn, Diseases; Keratitis, Dendritic; Trifluridine; Vidarabine

Topics: Acyclovir; Clinical Trials as Topic; Double-Blind Method; Encephalitis; Herpes Zoster; Humans; Immune Tolerance; Male; Middle Aged

One hundred and twenty-seven patients with suspected herpes simplex encephalitis were entered in a randomised, controlled comparative study of therapy with acyclovir 10 mg/kg, 8-hourly, versus vidarabine, 15 mg/kg daily, for 10 days. Consecutive patients were included and nearly all diagnosed cases of HSV-encephalitis in Sweden were enrolled in the study. The diagnosis of HSV-encephalitis was verified by demonstration of intrathecal herpes simplex virus (HSV) antibody production and by HSV cultivation, or antigen detection, in brain biopsy or necropsy material. Of 53 confirmed cases of HSV-encephalitis (corresponding to 2.3 cases per million inhabitants per year in Sweden), 51 (27 acyclovir, 24 vidarabine) were evaluable for therapeutic efficacy. The mortality was 19% in the acyclovir-treated group versus 50% in the vidarabine group (p = 0.04). At 12 month of observation 15 of 27 (56%) acyclovir recipients had no, or mild, sequelae compared with 3 of 24 (13%) vidarabine recipients (p = 0.002). Nineteen of 24 (79%) vidarabine-treated patients died or suffered severe sequelae, compared with 9 of 27 (33%) acyclovir-treated patients (p = 0.005). The effect of treatment was influenced by the level of consciousness at the start of therapy. The outcome for 20 vidarabine-treated patients above 30 years of age with HSE was similar to that for the 53 patients reported by an American collaborative study.

Topics: Acyclovir; Adolescent; Adult; Aged; Antibodies, Viral; Child; Child, Preschool; Clinical Trials as Topic; Encephalitis; Herpes Simplex; Humans; Infant; Middle Aged; Prospective Studies; Random Allocation; Vidarabine

Topics: Acyclovir; Antiviral Agents; Chickenpox; Clinical Trials as Topic; Encephalitis; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Idoxuridine; Infant, Newborn; Keratitis, Dendritic; Keratoconjunctivitis; Male; Vidarabine

127 patients with suspected herpes simplex encephalitis (HSE) were entered in a prospective randomised study of acyclovir 10 mg/kg 8-hourly versus vidarabine 15 mg/kg daily for 10 days. The patients were consecutive and nearly all Swedish cases of HSE were included; they were treated in six university infectious diseases departments. The diagnosis of HSE was verified by brain biopsy and/or antibody responses in serum and cerebrospinal fluid. Of 53 confirmed cases of HSE (corresponding to 2 X 3 cases per million inhabitants per year in Sweden), 51 (27 acyclovir, 24 vidarabine) were evaluable for analysis of efficacy. The mortality was 19% in the acyclovir-treated group versus 50% in the vidarabine group (p = 0.04). At 6 months of observation 15 (56%) of 27 acyclovir-treated patients had returned to normal life compared with 3 (13%) of 24 vidarabine-treated patients (p = 0.002); and the numbers who died or had severe sequelae were 9 (33%) and 19 (76%), respectively (p = 0.005). No important or new adverse events were recognised.

Topics: Acyclovir; Adolescent; Adult; Aged; Antibodies, Viral; Brain; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Encephalitis; Follow-Up Studies; Herpes Simplex; Humans; Infant; Infant, Newborn; Middle Aged; Prospective Studies; Random Allocation; Simplexvirus; Vidarabine

Topics: Acyclovir; Administration, Topical; Adolescent; Amantadine; Antiviral Agents; Chickenpox; Child; Clinical Trials as Topic; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Idoxuridine; Influenza, Human; Keratitis, Dendritic; Male; Rimantadine; Vidarabine

Guidelines for the prophylaxis or therapy of herpesvirus infections are shown in Table 1. Progress is so rapid in this area that frequent revisions of such guidelines will be necessary. Newer drugs or new formulations of older agents are constantly being developed. Combination therapies--e.g., interferon plus acyclovir--appear promising in laboratory models of herpesvirus infections and will undoubtedly receive clinical investigation in the years ahead. The problem of dealing with latent virus infections still eludes us, and major breakthroughs will be necessary before we can discuss cure of recurrent infections. Nevertheless, important strides have been made in the past few years, and further progress is predictable in the years ahead.

Topics: Acyclovir; Clinical Trials as Topic; Cytomegalovirus Infections; Encephalitis; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpesviridae Infections; Humans; Immune Tolerance; Infant, Newborn; Interferon Type I; Keratitis, Dendritic; Male; Vidarabine

Acyclovir (aciclovir) is a nucleoside analogue antiviral drug related to cytarabine, idoxuridine, trifluridine and vidarabine. In common with these earlier antivirals, acyclovir is active against some members of the herpesvirus group of DNA viruses. The efficacy of topical acyclovir has been convincingly demonstrated in ocular herpetic keratitis, and in initial and primary initial genital herpes infection, but little or no clinical benefit was seen when non-primary initial genital infections were assessed separately. Acyclovir ointment demonstrated little benefit in recurrent genital herpes but topical acyclovir cream decreased the course of the infection by 1 to 2 days. Orally and intravenously administered acyclovir were beneficial in initial genital herpes infections, and oral therapy shortened the duration of recurrent infections by 1 to 2 days but did not ameliorate pain. In non-immunocompromised patients with recurrent herpes simplex labialis, generally little clinical benefit was seen with the use of topical acyclovir ointment even when therapy was initiated during the prodromal phase, while topical acyclovir cream effected small but significant improvements in the clinical but not the symptomological course of the disease. However, in immunocompromised patients, both intravenous and topical acyclovir shortened the clinical course of herpes simplex virus infections occurring mainly on the lips, oral mucosa and face, and prophylaxis with either oral or intravenous acyclovir suppressed the appearance of recurrent lesions from latent virus for the period of drug administration, but acyclovir did not eradicate latent herpesviruses. In non-immunocompromised patients, intravenous acyclovir was shown to decrease the acute pain of zoster, especially in the elderly, but postherpetic neuralgia was not ameliorated. When immunocompromised patients were studied, intravenous acyclovir inhibited the progression of zoster infections and shortened the healing time and duration of viral shedding in patients with cutaneous disseminated zoster. However, acute and post-herpetic pain were not significantly affected. Well designed controlled studies are underway to establish the efficacy of acyclovir in herpes simplex encephalitis and cytomegalovirus infections in immunocompromised patients, infections due to Epstein-Barr virus, and neonatal herpesvirus infections. Despite some aspects of the drug's use which require further clarification, acyclovir will make a major imp

Topics: Acyclovir; Animals; Clinical Trials as Topic; Cytomegalovirus; Drug Resistance, Microbial; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Herpesvirus 4, Human; Humans; Immunity; Keratitis, Dendritic; Kinetics; Male; Mutagens; Recurrence

Herpes simplex encephalitis and neonatal herpes simplex virus infections are important consequences of herpes simplex virus infections of humans. The association of both diseases with significant mortality and morbidity has prompted intensive therapeutic trials designed to improve outcome. The NIAID Collaborative Antiviral Study Group has been able to demonstrate that vidarabine therapy decreases the mortality and improves morbidity for both herpes simplex encephalitis and neonatal herpes simplex virus infections. Nevertheless, mortality for both diseases is about 40% and many survivors are left with significant neurological impairment. With the hope of improving outcome, we initiated comparative trials of vidarabine and acyclovir for these two diseases. This report summarizes the status of these trials, which are still underway, with particular reference to the complexities of studies such as these. Because adequate numbers of patients for definitive statistical analyses have not been entered into the trial, data were assessed according to outcome for the entire group, irrespective of drug administered. The mortality of herpes simplex encephalitis and neonatal herpes simplex virus infections has been reduced to 34 and 30%, respectively, a decrease of approximately 10% for each disease. Further analyses await completion of the trials.

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Random Allocation; Time Factors; Vidarabine

Topics: Acyclovir; Clinical Trials as Topic; Control Groups; Encephalitis; Ethics, Medical; Guanine; Herpes Simplex; Humans; Patient Selection; Research Subjects; Therapeutic Human Experimentation

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Guanine; Herpes Simplex; Humans; Research Design; Vidarabine

Data on encephalitis in elderly patients are scarce. We aimed to describe the characteristics, aetiologies, management, and outcome of encephalitis in patients older than 65 years.. We performed an ancillary study of ENCEIF, a prospective cohort that enrolled all cases of encephalitis managed in 46 clinical sites in France during years 2016-2019. Cases were categorized in three age groups: (1) 18-64; (2) 65-79; (3) ≥ 80 years.. Elderly patients represent > 50% of adults with encephalitis in France, with higher proportion of L. monocytogenes and VZV encephalitis, increased risk of death, and sequels. The empirical treatment currently recommended, aciclovir and amoxicillin, is appropriate for this age group.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Coma; Encephalitis; France; Herpesvirus 3, Human; Humans; Infectious Encephalitis; Prospective Studies

Encephalitis is the inflammation of the brain parenchyma accompanied by mental or behavioral neurological dysfunction, sensory or motor deficits, speech or movement disorders, and seizure. Encephalitis is an acute, life-threatening emergency that requires prompt recognition and a systematic approach for appropriate management. Human herpes virus (HHV-7) is one of the causative agents of encephalitis. In this report, a three years and six months old girl admitted to the hospital with the complaints of fever, cough, gushing vomiting, and altered consciousness, with fever, neck stiffness and blurred consciousness in her physical examination, and positive HHV-7 DNA polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) was presented. The CSF biochemistry of the patient was normal, and lymphocytic pleocytosis was detected in the CSF. Electroencephalography of the case revealed a cerebral dysfunction and hyperexcitability due to background activity abnormalities, and a cytotoxic transient lesion of the splenium in cranial magnetic resonance imaging. A 14-day foscarnet treatment was given to the patient after she progressed under empirical acyclovir treatment and HHV-7 was found to be the causative agent in the CSF. The patient was cured with the treatment and was followed up on an outpatient basis without any sequelae. In general, HHV-7 is estimated to be a common cause of pediatric acute encephalitis cases. It has been observed in the literature that almost all of the HHV-7-associated encephalitis cases occur after the age of six years, suggesting that HHV-7 causes neurological disease in children as a late infection. This case was three years and six months old and it was thought that she had encephalitis during primary infection. With this case report, we contributed to the literature by presenting a case of encephalitis in an immunocompetent pediatric patient with a transient splenial lesion associated with HHV-7, which progressed with empirical acyclovir treatment and responded to foscarnet treatment.

Topics: Acyclovir; Antiviral Agents; Child; Encephalitis; Female; Foscarnet; Herpesvirus 7, Human; Humans; Infant

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

The SARS-CoV-2 virus, which causes COVID-19, could give rise to damage the nervous system. Many studies have been conducted on this topic, but few have focused specifically on encephalitis. The effect of SARS-CoV-2 on the clinical expression of other neurotropic viruses, such as Herpesviridae, is unknown.. We describe the cases of two young men (39 and 18 years old) in whom SARS-CoV-2 had been detected -reverse transcription polymerase chain reaction (RT-PCR)-, and with a clinical diagnosis and cerebrospinal fluid (CSF) analysis consistent with encephalitis. The first patient had a positive PCR for varicella zoster virus in CSF, while the second had a positive PCR for herpes simplex virus types 1 and 2. The first patient, who was recently diagnosed with human immunodeficiency virus, presented with fever, headache, vomiting, cough, inappropriate behaviour and epileptic seizures; the second was seen to have fever, headache, myalgia and exanthema. Both offered the same laboratory findings (lymphopenia and high interleukin 6). CSF showed pleocytosis with a predominance of monomorphonuclear cells, hyperproteinorrachia and normal glycorrhachia. A cranial CT scan showed only mild diffuse cerebral oedema in the first case. Both cases were treated with corticosteroids, antibiotics and acyclovir. The second progressed favourably, while the first did not.. Little is known about co-infection of SARS-CoV-2 with neurotropic viruses, such as Herpesviridae, and we have only limited evidence of direct neurological involvement of SARS-CoV-2, due to the technical difficulty of detecting it in the nervous system, thus making it important to take co-infection into account in order to be able to establish an early diagnosis and treatment to improve prognosis.. COVID-19 y encefalitis por herpesvirus.. Introducción. El virus SARS-CoV-2, causante de la COVID-19, podría generar lesiones en el sistema nervioso. Son múltiples los estudios relacionados con esto, pero escasos en cuanto a la encefalitis en particular. A su vez, se desconoce el efecto del SARS-CoV-2 sobre la expresión clínica de otros virus neurótropos, como los Herpesviridae. Casos clínicos. Se describen dos casos de varones jóvenes, de 39 y 18 años, con detección de SARS-CoV-2 –reacción en cadena de la polimerasa con transcripción inversa (RT-PCR)–, con diagnóstico clínico y análisis del líquido cefalorraquídeo (LCR) compatibles con encefalitis. En el primer paciente se obtuvo una PCR positiva para el virus de la varicela zóster en el LCR, mientras que, en el segundo, para el virus del herpes simple de los tipos 1 y 2. El primer paciente, con diagnóstico reciente positivo para el virus de la inmunodeficiencia humana, presentó fiebre, cefalea, vómitos, tos, conductas inapropiadas y crisis epiléptica; y el segundo, fiebre, cefalea, mialgias y exantema. Ambos compartieron hallazgos en la analítica (linfopenia e interleucina 6 elevada). En el LCR se observó pleocitosis con predominio de monomorfonucleares, hiperproteinorraquia y glucorraquia normal. La tomografía computarizada de cráneo sólo evidenció un edema cerebral difuso leve en el primer caso. En ambos casos se realizó un tratamiento con corticoides, antibióticos y aciclovir. En el segundo, la evolución fue favorable, mientras que en el primero, no. Conclusiones. Poco se conoce sobre la coinfección del SARS-CoV-2 con virus neurótropos, como los Herpesviridae, lo que se suma a la escasa evidencia de la afectación neurológica directa del SARS-CoV-2, debido a la dificultad técnica para su detección en el sistema nervioso, por lo que es importante considerar la coinfección para realizar un diagnóstico y un tratamiento precoces que mejoren el pronóstico.

Topics: Acyclovir; COVID-19; Encephalitis; Herpesvirus 3, Human; Humans; Male; SARS-CoV-2

Encephalitis, the most significant of the central nervous system (CNS) diseases caused by Herpes simplex virus 1 (HSV-1), may have long-term sequelae in survivors treated with acyclovir, the cause of which is unclear. HSV-1 exhibits a tropism toward neurogenic niches in CNS enriched with neural precursor cells (NPCs), which play a pivotal role in neurogenesis. NPCs are susceptible to HSV-1. There is a paucity of information regarding the influence of HSV-1 on neurogenesis in humans. We investigated HSV-1 infection of NPCs from two individuals. Our results show (i) HSV-1 impairs, to different extents, the proliferation, self-renewing, and, to an even greater extent, migration of NPCs from these two subjects; (ii) The protective effect of the gold-standard antiherpetic drug acyclovir (ACV) varies with viral dose and is incomplete. It is also subject to differences in terms of efficacy of the NPCs derived from these two individuals. These results suggest that the effects of HSV-1 may have on aspects of NPC neurogenesis may vary among individuals, even in the presence of acyclovir, and this may contribute to the heterogeneity of cognitive sequelae across encephalitis survivors. Further analysis of NPC cell lines from a larger number of individuals is warranted.

Topics: Acyclovir; Encephalitis; Herpes Simplex; Herpesvirus 1, Human; Humans; Neural Stem Cells; Neurogenesis

Few Japanese hospitals can perform in-house cerebrospinal fluid (CSF) polymerase chain reaction (PCR) to screen for herpes simplex virus, leading to patients being administered acyclovir (ACV) for several days. The FilmArray Meningitis/Encephalitis Panel (ME Panel) is a multiplex PCR test that can identify 14 major pathogens within 1 h. We aimed to investigate the efficacy of the ME Panel in children admitted with central nervous system infections in Japan.. We conducted a single-center, quasi-experimental study. The ME panel was introduced in April 2020. We outsourced the CSF samples to a laboratory during the pre-intervention period (April 2016 to March 2020) and performed the ME panel at our hospital during the post-intervention period (April 2020 to December 2021). Duration and dose of ACV and antibiotic use, length of stay (LOS) in the pediatric intensive care unit (PICU), and total LOS after testing were compared using the Mann-Whitney U test.. The number of cases in the pre- and post-intervention periods was 67 and 22 cases, respectively. The median duration of ACV decreased significantly from 6 days to 0 day (p < 0.001), and the median dose of ACV use decreased significantly from 14 vials to 0 vial (p < 0.001). No significant differences were noted in the total duration and dose of antibiotic use, LOS in PICU, and the total LOS after testing.. The introduction of ME panel may contribute to appropriate ACV use; however, there was no significant change in the duration and dose of antibiotic use or LOS.

Topics: Acyclovir; Anti-Bacterial Agents; Child; Encephalitis; Humans; Meningitis; Multiplex Polymerase Chain Reaction

In infections of the Central Nervous System (iCNS), rapid identification of causing pathogens is crucial for survival and to avoid long-term sequelae. Targeted therapy may reduce side effects and development of antibiotic resistance. New molecular-based syndromic tests such as the "meningitis/encephalitis panel" (MEP) allow accelerated pathogen identification from cerebrospinal fluid. We conducted a clinical study to evaluate the MEP's efficacy in paediatric patients.. Cohort study in a unique clinical setting by comparing the outcome data of two neighbouring Children's Hospitals in Germany which are comparable in size, catchment area and equipment but differ regarding availability of the MEP: study centre 1 (SC1): yes; SC2: no. The study population included 213 paediatric patients with a suspected iCNS (SC1: 106; SC2: 107), with comparable age, CRP at admission and frequency of intensive care. The primary outcome was total use of antibiotics.. Total antibiotic use per patient was numerically lower in SC1 than in SC2 (SC1: median 2.83 days; SC2 3.67 days; p = 0.671). Multiple linear regression analysis did not show a relevant association between MEP-availability and total antibiotic use (ß = 0.1, 95% confidence interval [-1.46; +1.67], p = 0.897). In the subcohort with suspected meningoencephalitis (SC1: 18, SC2: 17), duration of acyclovir treatment was shorter in SC1 than in SC2 (median 1.3 days vs. 2.7 days, descriptive p = 0.0397).. The add-on use of the MEP in paediatric patients with suspected iCNS was associated with a non-significant reduction in total antibiotic use, and with a reduced exposure to acyclovir in treated patients.

Topics: Acyclovir; Anti-Bacterial Agents; Child; Cohort Studies; Encephalitis; Humans; Meningitis; Multiplex Polymerase Chain Reaction

Central and peripheral nervous system involvement of COVID-19 has been reported in 25% of cases. COVID-19 is associated with encephalitis and most often presenting with confusion and disorientation, and mortality decreases with early diagnosis and treatment.The patient who was admitted with confusion and fever and found COVID-19 PCR positivity in both cerebrospinal fluid (CSF) and the nasopharyngeal swab is presented here. A 71-year-old female patient who underwent transsphenoidal pituitary tumor surgery 4 months ago, was in an acute confusional state with fluctuations in consciousness and agitation. It was suggested that bilateral temporal areas of the brain and paramedian region of the pons compatible with encephalitis in the T2 and FLAIR axial sections of magnetic resonance imaging (MRI). Nasopharyngeal and CSF SARS-CoV-2 RNA PCR was studied since thorax CT was compatible with COVID-19 pneumonia and in both samples, PCR was found positive. Encephalitis for toxic and metabolic causes was excluded. In this case, COVID-19 encephalitis was treated with dual antiviral (favipiravir and acyclovir) and steroid therapy. The uniqueness of this case is not only the presence of a very few reported cases of both Nasopharyngeal and CSF SARS-CoV-2 RNA PCR positivity but also previous history of transsphenoidal pituitary surgery 4 months ago.

Topics: Acyclovir; Aged; Antiviral Agents; COVID-19; Encephalitis; Female; Humans; Pituitary Diseases; RNA, Viral; SARS-CoV-2; Steroids

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

To determine whether the BioFire FilmArray Meningitis/Encephalitis (ME) panel is associated with decreased resource use for febrile infants. The ME panel has a rapid turnaround time (1-2 hours) and may shorten length of stay (LOS) and antimicrobial use for febrile well-appearing infants.. Retrospective cohort study of febrile well-appearing infants ≤60 days with cerebrospinal fluid culture sent in the emergency department from July 2017 to April 2019. We examined the frequency of ME panel use and its relationship with hospital LOS and initiation and duration of antibiotics and acyclovir. We used nonparametric tests to compare median durations.. The ME panel was performed for 85 (36%) of 237 infants. There was no difference in median hospital LOS for infants with versus without ME panel testing (42 hours, interquartile range [IQR] 36-52 vs 40 hours, IQR: 35-47, P = .09). More than 97% of infants with and without ME panel testing were initiated on antibiotics. Patients with ME panel were more likely to receive acyclovir (33% vs 18%; odds ratio: 2.2, 95%: confidence interval 1.2-4.0). There was no difference in median acyclovir duration with or without ME panel testing (1 hour, IQR: 1-7 vs 4.2 hours, IQR: 1-21, P = .10). When adjusting for potential covariates, these findings persisted.. ME panel use was not associated with differences in hospital LOS, antibiotic initiation, or acyclovir duration in febrile well-appearing infants. ME panel testing was associated with acyclovir initiation.

Topics: Acyclovir; Anti-Bacterial Agents; Encephalitis; Fever; Humans; Infant; Meningitis; Retrospective Studies

In recent years, there have been an increasing number of reports on overlapping antibodies in autoimmune encephalitis (AE). There are various types of overlapping antibodies, but the clinical significance of each type is not yet clear. Glial antibodies, such as MOG, AQP4, and especially NMDAR, can be detected in patients with AE. However, little is known about the overlapping antibodies of anti-glial fibrillary acidic protein (GFAP), and only a few case reports have described this overlap. Case presentation The patient was a 7-year-old girl with recurrent intermittent fever and seizures, and viral encephalitis was diagnosed at the beginning of the disease. She was discharged after treatment with acyclovir, high-dose immunoglobulins, and valproic acid as an antiseizure medication. Subsequently, the patient still had occasional seizures and abnormal behavior, and the anti-NMDAR antibody test was positive (1:3.2). She was treated with high-dose methylprednisolone and antiseizure therapy. Approximately half a year later, the patient experienced fever and seizures again, serum GFAP IgG was 1:100, and a head MRI indicated new lesions. Improvement was achieved after repeated high-dose methylprednisolone and continuous prednisone anti-inflammatory therapy.. Anti-NMDAR encephalitis combined with GFAP-IgG is uncommon, and repeated tests for AE-associated antibodies may be required in patients with recurrent encephalitis. Compared with cerebrospinal fluid antibody-positive children, serum GFAP IgG-positive children should be comprehensively diagnosed according to their clinical manifestations. It is worth considering whether overlapping antibody syndrome can still be an issue for patients with AE who recover and have negative antibodies after a few months if disease recurrence and new antibodies are detected.

Topics: Acyclovir; Anti-Inflammatory Agents; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Autoantibodies; Child; Encephalitis; Female; Hashimoto Disease; Humans; Immunoglobulin G; Methylprednisolone; Neoplasm Recurrence, Local; Prednisone; Seizures; Syndrome; Valproic Acid

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

Topics: Acute Kidney Injury; Acyclovir; Aged; Antibodies, Viral; Antiviral Agents; Confusion; Diagnosis, Differential; DNA, Viral; Encephalitis; Encephalitis, Varicella Zoster; Exanthema; Hashimoto Disease; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Magnetic Resonance Imaging; Male; Meningoencephalitis; Neuroimaging; Recurrence

Topics: Acyclovir; Adult; Antiviral Agents; Diagnosis, Differential; Encephalitis; Female; Hashimoto Disease; Humans; Kenya; Magnetic Resonance Imaging; Tertiary Care Centers

Prompt initiation of empiric therapy is common practice in case of suspected meningitis or encephalitis. However, in children the most common pathogens are viruses that usually do not require and are not covered by the applied anti-infective treatment. Novel multiplex PCR (mPCR) panels provide rapid on-site diagnostic testing for a variety of pathogens. This study compared empiric antibiotic and acyclovir usage before and after the introduction of an on-site FilmArray Meningitis/Encephalitis Panel (FA ME Panel).. We retrospectively compared data for empiric antibiotic and acyclovir usage between pediatric patients with suspected central nervous system (CNS) infection receiving mPCR testing and a matched historical control group. Patients were matched by age and suspected CNS infection. We included all patients for whom empiric antibiotics and/or acyclovir were prescribed.. Each study group consisted of 46 patients with 29 (63.0%) infants and 17 (37.0%) older children. A viral pathogen was diagnosed in 5/46 (10.9%) patients in the control group (all enteroviruses) and in 14/46 (30.4%) patients in the mPCR group (enterovirus n = 9; human herpesvirus 6 (HHV-6) n = 5), (p = 0.038)). Length of Therapy (LoT) and Days of Therapy (DoT) for antibiotics were significantly lower for infants (4.0 vs. 3.0, p = 0.038 and 8.0 vs. 6.0, p = 0.015, respectively). Acyclovir therapy was significantly shorter for both, infants and older children (3.0 vs. 1.0 day, p < 0.001 for both age groups).. The findings of our study suggest that the introduction of a FA ME Panel into clinical routine procedures is associated with a significantly reduced LoT and DoT of empiric anti-infective treatment in children with suspected meningoencephalitis. The largest effect was observed in infants.

Topics: Acyclovir; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Encephalitis; Female; Hospitals, Pediatric; Humans; Infant; Male; Meningitis; Retrospective Studies; Young Adult

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Brain Diseases; Cefotaxime; Corpus Callosum; Diagnosis, Differential; Encephalitis; Humans; Influenza, Human; Male; Middle Aged

EBV associated nervous system complications includes encephalitis, meningitis, cerebellitis, polyradiculomyelitis, transverse myelitis, cranial and peripheral neuropathies, and psychiatric abnormalities are usually more commonly seen in immunocompromised patients and rarely in immunocompetent patients. Here we are reporting a 13 years old boy developed headache, malaise, sore throat and low back pain with radiation to both lower limbs. Next day he felt numbness below umbilicus followed by acute onset weakness in both lower limbs and urinary retention. Motor exam revealed proximal muscle power MRC grade 4/5 and distal power 1/5 in right lower limb and proximal power 4-/5 and distal power 0/5 in left lower limb with normal power in both upper limbs. Deep tendon reflexes were bilaterally normal except absent ankle reflexes. Both plantars were mute. All the modalities of sensation including pain, touch, temperature, joint position and vibration were impaired below umbilicus. Routine investigations were normal. The magnetic resonance imaging (MRI) of thoracic spine showed intramedullary lesion in conus, which was iso-hyperintense on T1-weighted and hyperintense on T2- weighted images extending from D12thoracic vertebral level to L1 with cord expansion (Figures 1, 2). The MRI features were suggestive of conus myelitis. Cerebrospinal fluid (CSF) analysis revealed increased protein, normal cells, glucose and Chloride. CSF Polymerase chain reaction (PCR) was positive for Epstein Barr virus . The clinical and imaging findings were consistent with the diagnosis of myelitis and responded well to steroid plus acyclovir treatment. The clinicians should be aware of such uncommon etiology of a common disease.

Topics: Acyclovir; Adolescent; Encephalitis; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Magnetic Resonance Imaging; Male; Myelitis, Transverse

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

A 45-year-old man was presented at the emergency department with altered neurological status and a 1-day history of diarrhoea and fever. The patient's sexual history revealed multiple male partners. As bacterial meningitis or viral encephalitis was suspected, treatment was started accordingly. Cerebrospinal fluid investigations only showed a slight increase of leucocytes, and microbiological studies remained negative. Stool culture revealed

Topics: Acyclovir; Amoxicillin; Anti-Bacterial Agents; Ceftriaxone; Diarrhea; Drug Therapy, Combination; Dysentery, Bacillary; Encephalitis; Feces; Fever; Humans; Male; Middle Aged; Sexual and Gender Minorities; Shigella flexneri; Treatment Outcome; Unsafe Sex

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

Topics: Acyclovir; Aged; Encephalitis; Factor XIII; Factor XIII Deficiency; Female; Hashimoto Disease; Humans

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

Parvovirus B19 (PVB19) has rarely been identified as a cause of encephalitis in immunocompetent adults, in whom clinical information regarding PVB19 encephalitis has remained unclear. Herein, we report the clinical presentations, laboratory and imaging findings, and treatment outcomes of five immunocompetent adults with PVB19 encephalitis. Although none of the patients showed any distinctive features of PVB19 infection, they showed various clinical manifestations, including one instance of brainstem involvement. Additionally, immunotherapy can be considered an effective approach, especially in immunocompetent adults with PVB19 encephalitis who are resistant to the initial management.

Topics: Acyclovir; Adult; Antiviral Agents; Drug Administration Schedule; Encephalitis; Female; Humans; Immunocompetence; Immunoglobulins, Intravenous; Magnetic Resonance Imaging; Male; Methylprednisolone; Middle Aged; Parvoviridae Infections; Parvovirus B19, Human; Seizures; Treatment Outcome; Viral Load

Topics: Acyclovir; Adult; Encephalitis; Herpes Simplex; Herpesvirus 3, Human; Humans; Male; Meningitis, Viral; Meningoencephalitis; Simplexvirus; Valacyclovir; Valine; Varicella Zoster Virus Infection

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

We report a case of a 62-year-old female with seizures and encephalitis. Molecular testing of the patient's cerebrospinal fluid was positive for both herpes simplex virus 1 and 2 (HSV-1 and HSV-2). To our knowledge, this is the first report of simultaneous detection of HSV-1 and HSV-2 in cerebrospinal fluid.

Topics: Acyclovir; Antiviral Agents; DNA, Viral; Encephalitis; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Middle Aged; Seizures

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

Topics: Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Brain Stem; Encephalitis; Herpes Zoster; Herpes Zoster Oticus; Humans; Male; Methylprednisolone; Middle Aged

A 26-year-old male was admitted because of a fever, headache and disturbance of consciousness with lymph node swelling of the neck two days after developing a rash. A neurological examination revealed restlessness with irritability in response to sensory stimuli, such as an injection. Diffusion-weighted brain magnetic resonance imaging (MRI) revealed a hyperintense ovoid lesion in the splenium of the corpus callosum, which showed a low coefficient in the ADC map: the lesion disappeared after 22 days. An enzyme immunoassay (EIA) of the serum and cerebrospinal IgM were positive for rubella virus. The patient was therefore diagnosed with rubella encephalitis. He recovered gradually and was discharged on day 19 after the onset of symptoms without any sequelae. To our knowledge, this is the first case of rubella encephalitis presenting as clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). Although the exact mechanism underlying the development of rubella encephalitis is not well established, this case indicated that our patient had an immune-mediated secondary encephalitis. According to the survey of the pandemic of rubella from 2012 to April 2013 in Japan, the incidence of rubella encephalitis is thought to be relatively higher than was previously noted. This emphasizes the importance of vaccination for preventing encephalitis.

Topics: Acyclovir; Adult; Antibodies, Viral; Antiviral Agents; Biomarkers; Corpus Callosum; Diffusion Magnetic Resonance Imaging; Encephalitis; Encephalitis, Viral; Humans; Immunoenzyme Techniques; Immunoglobulin M; Infusions, Intravenous; Male; Rubella; Rubella virus; Severity of Illness Index; Treatment Outcome

A case of herpes simplex virus (HSV) encephalitis in a neonate after delivery from a woman whose genital HSV infection had been treated with acyclovir is reported. The main approach to prevent genital HSV infection in the neonate is interruption of transmission at the time of delivery. Guidelines for prophylactic therapy with acyclovir have been established, but the risk of neonatal infection remains. A fever began to develop in a male neonate delivered vaginally from a 35-year-old woman. Treatment with intravenous acyclovir was started on the basis of a diagnosis of HSV encephalitis, because polymerase chain reaction was positive for HSV in the cerebrospinal fluid. The mother had had a first genital HSV infection during the second trimester, but treatment with injected acyclovir had caused the blisters and erosion to resolve by the time of delivery. Important steps for preventing neonatal HSV infection are the appropriate treatment of mothers with a history of genital HSV infection, the assessment of delivery methods, and the appropriate treatment of neonates.

Topics: Acyclovir; Adult; Delivery, Obstetric; Encephalitis; Female; Herpes Genitalis; Humans; Infant, Newborn; Magnetic Resonance Imaging; Male; Pregnancy; Simplexvirus

A 23-year-old gentleman with no significant medical history other than obesity was admitted with a history of balance problems, double vision and strange behaviour following a fall from bed. Systems examination was unremarkable. The patient was given intravenous acyclovir and intravenous ceftriaxone given the suspicion of encephalitis/meningitis. Investigations including routine bloods, CT/MRI Head and lumbar puncture were unremarkable. Within 48 h of commencing intravenous acyclovir, there was a marked deterioration in renal function. On stopping acyclovir therapy, renal function improved back to baseline. No other cause for deterioration in renal function was identified. The most likely cause for acute renal failure was secondary to acyclovir therapy. This has been well documented and is due to intratubular crystal precipitation. Moreover, in this case nephrotoxicity is likely secondary to the large boluses of intravenous acyclovir that had been given as prescribed according to the total body weight.

Topics: Accidental Falls; Acute Kidney Injury; Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Ceftriaxone; Encephalitis; Humans; Male; Meningitis; Obesity; Young Adult

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

Human parvovirus B19 (PVB19) causes erythema infectiosum or 5(th) disease in childhood, which mainly affects children between 3 and 15 years of age. PVB19 infections have also been described in association with a variety of neurologic manifestations including encephalitis.. This 3-year 8-month-old boy developed febrile encephalitis (mental status change with seizures and left limb hypertonia) associated with a rash. The electroencephalographs revealed focal slowing with some spikes in front of the left centro-temporo-occipital areas ; bacteriological and biochemical cerebrospinal fluid (CSF) analysis were normal, brain radiologic studies (tomography and magnetic resonance imaging) were normal. The diagnosis of encephalitis associated with PVB19 primo infection was based on viral DNA detection in the serum and CSF using PCR and on the specific immunoglobulin M (without immunoglobulin G) detection in the serum.. In France, encephalitis etiology is unknown in 48% of the cases. PVB19 accounts for 4.3% of undiagnosed meningoencephalitis in children. Although there is no specific sign, seizures and rash are reported in about one-half and one-quarter of cases, respectively.. Even if PVB19 research is not cited in the French or American infectious disease society recommendations on the diagnosis and management of infectious encephalitis, this virus may be responsible, especially in cases of child febrile rash. Therefore, PVB19 research seems reasonable if the clinical presentation is concordant in children due to its diagnostic simplicity and efficacy.

Topics: Acyclovir; Anticonvulsants; Antiviral Agents; Child, Preschool; Diazepam; Drug Therapy, Combination; Encephalitis; Humans; Male; Parvoviridae Infections; Parvovirus B19, Human; Treatment Outcome

Since the outbreak of novel influenza A (H1N1) in 2009, various neurological complications have been cited. We described a male patient with H1N1-associated encephalopathy/encephalitis presenting with severe neurological symptoms and signs. Residual neurological sequelae were dominant. This is the first report of extensive cortical-subcortical necroses over the bilateral frontal-parietal areas based on an MRI study.

Topics: Acyclovir; Adult; Anti-Bacterial Agents; Antiviral Agents; Brain; Cerebral Angiography; Electroencephalography; Encephalitis; Hemiplegia; Humans; Hypnotics and Sedatives; Influenza A Virus, H1N1 Subtype; Influenza, Human; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Muscle Rigidity; Nervous System Diseases; Oseltamivir; Propofol; Tomography, X-Ray Computed; Tremor

Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) is a severe multiorgan reaction with reactivation of herpesviruses. Various features are often seen during the course of the disease. Many aspects of this syndrome suggest close similarities between DIHS/DRESS and graft-versus-host disease. We describe a patient with phenobarbital-induced hypersensitivity syndrome who revealed syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with limbic encephalitis during the course of the disease. In view of previous reports that SIADH and limbic encephalitis are caused by reactivation of latent herpesviruses after transplantation, both conditions may be secondarily caused by reactivation of latent herpesviruses, which is typically observed in DIHS/DRESS. These neurological symptoms should be added to a growing list of important complications of DIHS/DRESS because of the high mortality rate associated with them.

Topics: Acyclovir; Aged; Anticonvulsants; Antiviral Agents; Coma; Drug Hypersensitivity; Encephalitis; Epilepsy; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Phenobarbital; Syndrome; Treatment Outcome

This study was undertaken to investigate possible immune mechanisms in fatal herpes simplex virus type 1 (HSV-1) encephalitis (HSE) after HSV-1 corneal inoculation. Susceptible 129S6 (129) but not resistant C57BL/6 (B6) mice developed intense focal inflammatory brain stem lesions of primarily F4/80(+) macrophages and Gr-1(+) neutrophils detectable by magnetic resonance imaging as early as day 6 postinfection (p.i.). Depletion of macrophages and neutrophils significantly enhanced the survival of infected 129 mice. Immunodeficient B6 (IL-7R(-/-) Kit(w41/w41)) mice lacking adaptive cells (B6-E mice) and transplanted with 129 bone marrow showed significantly accelerated fatal HSE compared to B6-E mice transplanted with B6 marrow or control nontransplanted B6-E mice. In contrast, there was no difference in ocular viral shedding in B6-E mice transplanted with 129 or B6 bone marrow. Acyclovir treatment of 129 mice beginning on day 4 p.i. (24 h after HSV-1 first reaches the brain stem) reduced nervous system viral titers to undetectable levels but did not alter brain stem inflammation or mortality. We conclude that fatal HSE in 129 mice results from widespread damage in the brain stem caused by destructive inflammatory responses initiated early in infection by massive infiltration of innate cells.

Topics: Acyclovir; Animals; Antiviral Agents; Bone Marrow Transplantation; Brain Stem; Encephalitis; Eye; Flow Cytometry; Herpes Simplex; Herpesvirus 1, Human; Inflammation; Leukocyte Reduction Procedures; Macrophages; Mice; Mice, Knockout; Neutrophils; Receptors, Interleukin-7; Stem Cell Factor; Survival Analysis; T-Lymphocyte Subsets; Virus Shedding

In order to investigate the antiviral effect of chinonin against Herpes simplex virus (HSV), the encephalitis model in mice and skin infection model in guinea pigs were established by HSV- I and HSV-II infection respectively. Acyclovir was used as the positive reference drug to evaluate the antiviral capacity of chinonin. Chinonin showed an obvious therapeutic effect on encephalitis in mice at doses of 25 and 50 mg/kg. At both dosages, chinonin demonstrated stronger protection than acyclovir (1 and 5 mg/kg) to the infected mice from death. It was also found that chinonin could treat the skin infection in guinea pigs effectively. The therapeutic effect of chinonin was similar to that of acyclovir (5 mg/kg) at 25 mg/kg but obviously better than that at 50 and 75 mg/ kg. In conclusion, chinonin is a potential candidate for the treatment against HSV.

Topics: Acyclovir; Animals; Antiviral Agents; Encephalitis; Glycosides; Guinea Pigs; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Mice; Simplexvirus; Skin Diseases, Infectious; Xanthenes; Xanthones

Topics: Acute Disease; Acyclovir; Adrenal Cortex Hormones; Cerebellar Diseases; Child; Encephalitis; Gait Ataxia; Humans; Hydrocephalus; Magnetic Resonance Imaging; Male

Herpes simplex virus type 2 (HSV-2) encephalitis is rare especially during pregnancy. In immunocompetent patients, HSV-2 meningitis (contrary to HSV-1 meningitis) is usually mild, without encephalitis. We report a rare case of maternal HSV-2 encephalitis following Cesarean section. The woman had no symptomatic genital lesion, and the infant was not infected. The route of meningeal infection (neuronal or hematogenous) is discussed.

Topics: Acyclovir; Adult; Antiviral Agents; Cesarean Section; Encephalitis; Female; Herpes Simplex; Humans; Pregnancy; Pregnancy Complications, Infectious

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

Herpes simplex viruses (HSV) are responsible for neurological disorders that require rapid diagnostic methods and specific antiviral therapy. During 1997, 1431 cerebrospinal fluid samples (CSF) collected from 1339 patients with neurological disorder presentations were processed for HSV detection. Eleven patients were positive for HSV, seven presenting with encephalitis (6/7 due to HSV1) and 4 with aseptic meningitis (4/4 due to HSV2). The incidence of HSV encephalitis was 2.33 cases / 10(6) inhabitants/year. Among encephalitis (HSV encephalitis) cases, 1 patient died due to the late implementation of antiviral therapy, and sequelae were observed in 4 cases. No sequelae were observed in aseptic meningitis cases. Four HSV encephalitis cases were monitored by PCR detection in CSF. Despite acyclovir therapy, PCR remained positive in CSF up to 20 days in 2 cases. This result suggest that the antiviral treatment for HSV encephalitis should be monitored by PCR detection of HSV in CSF.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Central Nervous System Infections; Cerebrospinal Fluid; Child; Child, Preschool; DNA, Viral; Encephalitis; Female; Follow-Up Studies; France; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Incidence; Infant; Male; Meningitis, Aseptic; Middle Aged; Polymerase Chain Reaction

The effect of acyclovir treatment on viral burden and the expression of immunologic nitric oxide synthase (iNOS) within brains of 42 HSV-1 F infected mice was studied by using a titration PCR assay for HSV-1 DNA and a semiquantitative RT-PCR for iNOS mRNA. iNOS mediated NO-production may possibly be involved in secondary mechanisms of brain injury following virus infection, which may account for treatment failures in human herpes simplex virus encephalitis (HSVE). Following infection, a parallel increase of iNOS mRNA and HSV-1F-DNA occurred with peaks after 7 days that were both significantly lower under acyclovir treatment. Six months post infection viral load had declined, but iNOS mRNA expression in both treated and untreated mice was still enhanced as compared with mock infected controls. This suggests that acyclovir decreases iNOS expression via inhibition of viral replication shortly after infection but fails to influence elevated iNOS within the brain late in the course of experimental HSVE.

Topics: Acyclovir; Animals; Antiviral Agents; Brain; DNA, Viral; Encephalitis; Female; Herpes Simplex; Herpesvirus 1, Human; Immunologic Techniques; Mice; Mice, Inbred Strains; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Reference Values; RNA, Messenger; Time Factors; Viral Load

The anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guani ne (A-5021) was evaluated in murine cells and in several murine models of herpes simplex virus (HSV) infection. Against HSV type 1 (HSV-1), A-5021 was 15-30- and 30-60-fold more active, and against HSV type 2 (HSV-2), it was 2- and 8-fold more active than acyclovir and penciclovir in Balb/3T3 cells, respectively. When antiviral compounds were administered orally (once daily) to mice infected intraperitoneally with HSV-1 (Tomioka), A-5021 was more active than acyclovir or famciclovir in spite of its relatively low oral bioavailability. A-5021 was as active as penciclovir when the antiviral compounds were given intravenously (three times daily) to mice infected intraperitoneally with HSV-2 (186). In mice with a cutaneous HSV-1 (KOS) infection, three times daily oral therapy with A-5021 at 25 mg/kg per day produced more significant reduction in severity of skin lesions than equivalent treatment with acyclovir or famciclovir. In mice infected intracerebrally with HSV-1 (Tomioka), complete survival was observed in the group treated intravenously with A-5021 at 25 mg/kg per day (three times daily), while more than 50% of mice died in the groups treated intravenously with acyclovir of up to 100 mg/kg per day (three times daily). Moreover, A-5021 was more effective than acyclovir in clearing infectious virus from the brain. These findings demonstrate that A-5021 has potent anti-HSV activity in several murine models.

Topics: 3T3 Cells; Acyclovir; Administration, Oral; Animals; Antiviral Agents; Area Under Curve; Disease Models, Animal; Drug Evaluation; Encephalitis; Guanine; Herpes Simplex; Injections, Intravenous; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Peritoneum; Simplexvirus; Skin; Survival Rate

We reported a case of non-herpetic acute encephalitis with unilateral temporal cortex lesion revealed by MR imaging and SPECT study. The patient was an eighteen years old woman who developed tonic-clonic seizure after common cold symptom. She was healthy before this episode. Neurological abnormality was only a single convulsion at onset and there was no other abnormal physical and neurological signs except for low grade fever. Electroencephalogram showed spike and slow wave complex of 2 Hz focused on a right posteriotemporal point (T 6) and an MR FLAIR (fluid-attenuated inversion recovery) image revealed a high signal intensity area at right temporal cortex. There was a decrease of cerebral blood flow in the same portion on SPECT study. This lesion was obscure on T1 and T2 MR images. Cerebrospinal fluid showed pleocytosis with normal glucose level and protein concentration. Bacterial and fungal cultures of CSF were negative and a detection of tubercule bacillus by PCR hybridization method was also negative. Although CSF findings suggested viral infection of CNS, virological study could not demonstrate infections of herpes simplex virus type 1, type 2, varicella-zoster virus, cytomegalovirus, measles virus, mumps virus, Japanese encephalitis virus, and influenza virus type A and B. After infusion of acyclovir and antibiotics, the patient was discharged from our hospital without sequelae of encephalitis. EEG was normal at this point and a high intensity area of MR FLAIR image disappeared two months later. SPECT findings were normalized six months later. The encephalitis presenting unilateral temporal cortex lesion without the infection of herpes simplex virus is thought to be very rare. Our case was distinguished from non-herpetic acute limbic encephalitis by an extent of the lesion and clinical manifestations. MR FLAIR image was useful for the detection of the lesion in this case.

Topics: Acute Disease; Acyclovir; Adolescent; Antiviral Agents; Diagnosis, Differential; Encephalitis; Female; Humans; Image Enhancement; Magnetic Resonance Imaging; Temporal Lobe; Treatment Outcome

EEG has been used widely in diagnosing encephalitis, as it demonstrates rather typical abnormalities, especially in herpes simplex virus encephalitis (HSVE). We analysed 204 EEG recordings from 98 consecutive acyclovir-treated patients with acute encephalitis between 1984 and 1994. Periodic complexes (PC) in the acute phase predicted poor outcome (Kendall tau 0.40, P < 0.001). However, unlike in many other diseases, e.g. stroke and intracerebral haemorrhage, the diffuse slowing of the background activity at acute phase did not predict outcome (Kendall tau -0.6, P = 0.35). At follow-up, the emergence of diffuse slow background activity was significantly associated with a less favourable outcome (Kendall tau 0.33, P = 0.0016). Among clinical variables, only epileptic seizures early during the course of the disease correlated significantly with outcome. EEG does have value as a prognostic indicator in acute encephalitides, but it seems that diffuse slowing of background activity or irritative features acutely are not as important as previously thought, based on the experiences of the pre-acyclovir era.

Topics: Acute Disease; Acyclovir; Adult; Antiviral Agents; Electroencephalography; Encephalitis; Female; Herpes Simplex; Humans; Male; Middle Aged; Regression Analysis; Treatment Outcome; Virus Diseases

Two patients with presumed encephalitis lethargica are presented with clinical features suggestive of two forms of the disease described by Von Economo: One patient had a psychosis and a mute-akinetic syndrome associated with myoclonus. The second patient presented with a psychosis and fever, developing severe dyskinesias involving the mouth, trunk and limbs, together with respiratory irregularities and presumed hypothalamic disturbance and disturbance of consciousness. In both cases, initial cerebrospinal fluid (CSF) examination revealed an elevated white cell count (predominantly lymphocytes), elevated protein in case 2, and oligoclonal bands in both cases. Computed tomography (CT) brain scan was normal but in both cases EEG revealed diffuse slow wave activity. A 18F-Dopa positron emission tomography (PET) scan in case 2 was normal. The medical management of both patients is discussed. In case 1, L-Dopa improved the akinesia, while the myoclonus responded to clonazepam. In case 2, the severe dyskinesias failed to respond to a number of drugs, and she ultimately required paralysis to relieve her almost continuous movements. Both patients responded rapidly and dramatically to intravenous methylprednisolone. We suggest that steroid treatment should be considered in the acute phase of patients with features suggestive of encephalitis lethargica.

Topics: Acyclovir; Adult; Anti-Inflammatory Agents; Antiviral Agents; Encephalitis; Female; Humans; Injections, Intravenous; Methylprednisolone; Movement Disorders; Myoclonus; Sleep Stages

Effective diagnosis and treatment of cytomegalovirus infection of the nervous system in AIDS patients has been limited by a lack of sensitive diagnostic measures. Retrospective series suggest a poor prognosis for cytomegalovirus encephalitis with rapid mortality. Polymerase chain reaction amplification of cytomegalovirus DNA allows detection in CSF that appears specific for CNS infection. In this series of seven patients with CNS cytomegalovirus infection in AIDS, four patients responded to therapy. Serial determinations of cytomegalovirus DNA in CSF in five patients revealed persistent detection in two treatment failures and absence of detection in three responders on subsequent CSF samples. A prospective trial to determine optimal therapy and to confirm the utility of cytomegalovirus DNA in CSF as a marker of the course of cytomegalovirus infection in the CNS is warranted and should consider prior therapy for cytomegalovirus, prior opportunistic infections, and leukoencephalopathy as potential prognostic variables.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Base Sequence; Cerebrospinal Fluid; Cytomegalovirus; Cytomegalovirus Infections; DNA Primers; Encephalitis; Foscarnet; Ganciclovir; Genes, Immediate-Early; HIV Seropositivity; Humans; Male; Meningitis; Molecular Sequence Data; Polymerase Chain Reaction; Prognosis; Sensitivity and Specificity; Spinal Cord Diseases

We describe three patients who suffered from neurological complications to varicella-zoster virus infections. One had polyradiculoneuritis, another myelitis, and a third suffered from focal encephalitis. These patients were all treated with acyclovir, and showed good recovery within a few days. The diagnosis must be based on clinical characteristics, together with virological and immunological tests. The indications for antiviral treatment are discussed.

Topics: Acyclovir; Adult; Encephalitis; Female; Herpes Zoster; Humans; Male; Myelitis; Polyradiculoneuropathy

The creatine kinase/creatine phosphate (CK/CrP) system plays an important role in cellular energy homeostasis. CK isoenzymes, which reversibly generate ATP from CrP, are compartmentalized at cellular sites where energy is produced or utilized. It has been noted that the expression of CK is induced in cells infected by several DNA viruses, implicating a role for cellular energy modulation as an important step for efficient viral replication. A CK substrate analog, 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine; CCr), was tested in vitro for antiviral activity against a variety of herpes viruses and RNA viruses. Several members of the human herpes virus family were found to be sensitive to CCr, including herpes simplex types 1 and 2 (HSV-1 and HSV-2). varicella-zoster virus, and cytomegalovirus. When administered to mice infected vaginally with HSV-2, CCr significantly reduced mortality, reduced vaginal lesion scores, and lowered the titers of recoverable virus. This treatment combined with acyclovir appeared to enhance the antiviral effects of acyclovir. In a second model, mice infected intraperitoneally with HSV-2 and treated with CCr showed a significant increase in survival compared to placebo. We conclude that CCr is the first example of a new class of antiviral compounds that target the CK/CrP system.

Topics: Acyclovir; Animals; Creatinine; Disease Models, Animal; Drug Resistance, Microbial; Drug Therapy, Combination; Encephalitis; Female; Guanosine Triphosphate; Herpes Genitalis; Herpesviridae; Herpesviridae Infections; Humans; Mice; Microbial Sensitivity Tests; RNA Viruses; Survival Rate; Virus Replication

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

Brainstem encephalitis is an unusual infection caused by a variety of agents, among them the herpes simplex (HS) virus. The difficulty of establishing a diagnosis by neurophysiological and radiological examination is greater in this type of encephalitis than in the usual form produced by HS. We describe a fatal case of brainstem encephalitis. Inflammatory and necrotic lesions in the pous and medulla confirmed the clinical diagnosis, while the etiology was determined by immuno-histo-chemical techniques and viral culture of the cerebral parenchyma. Early diagnosis of this form of encephalitis, based on new virological techniques, allows more effective antiviral treatment.

Topics: Acyclovir; Antibodies, Monoclonal; Brain Stem; Encephalitis; Fatal Outcome; Humans; Immunohistochemistry; Microglia; Middle Aged; Simplexvirus

The early use of intravenous acyclovir in herpes simplex encephalitis (HSE) is essential. However, rapid diagnostic tests are not freely available. Hence, all patients with suspected encephalitis may need to be commenced on acyclovir. In our study, of 34 patients with suspected encephalitis, only two eventually had HSE confirmed, 19 had encephalitis not due to herpes simplex and in 13 a non-encephalitis illness was finally diagnosed. Guidelines for the use of acyclovir in suspected encephalitis are given aimed at minimizing the drug cost whilst still protecting all cases of presumed HSE.

Topics: Acyclovir; Drug Administration Schedule; Encephalitis; Herpes Simplex; Humans; Infusions, Intravenous; Retrospective Studies; Time Factors

Morbidity in rubella is generally mild, and neurological complications are rare, varying from 1:6000-1:24,000. We describe an 11-year-old girl with severe manifestations of rubella encephalitis. The onset of encephalitis most often occurs within 1-6 days after development of the typical rash. Neurological features vary and include encephalitis, carotid artery thrombosis, myelitis, optic neuritis, Guillain-Barre syndrome, and peripheral neuritis. Rubella should be considered in the differential diagnosis of encephalitis despite the current vaccination program in Israel. Such cases should be prevented by encouraging widespread early childhood vaccination.

Topics: Acyclovir; Ceftriaxone; Child; Diagnosis, Differential; Encephalitis; Female; Humans; Rubella

A case of herpes simplex encephalitis in a previously healthy 17-month-old girl relapsing 1 week after completion of a 10-day acyclovir therapy is described. The child responded favourably to a second 10-day course with acyclovir. The time of relapse and the satisfactory response to a second course of acyclovir treatment indicate that the first course of therapy was inadequate for eradication of herpes simplex virus infection.

Topics: Acyclovir; Drug Administration Schedule; Encephalitis; Female; Herpes Simplex; Humans; Infant; Recurrence

A 78-year-old man developed herpes zoster virus (HZV) encephalitis. Initially, treatment with aciclovir (750 mg per day) improved CSF cell count and protein level. During the treatment, however, encephalitis in the patient deteriorated in spite of the treatment with aciclovir, suggesting that HZV in the patient had become resistant to aciclovir. Subsequent treatment with vidarabine (600 mg per day, for 15 days) resulted in dramatic improvement in CSF pleocytosis. About two months after the discontinuation of vidarabine, the CSF cell count was normal. The patient became alert gradually, but his amnestic syndrome remained unchanged. Vidarabine may be recommended in the treatment of HZV encephalitis when aciclovir is not effective.

Topics: Acyclovir; Aged; Cell Count; Cerebrospinal Fluid; Drug Resistance; Encephalitis; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Vidarabine

Authors report about a boy with Rasmussen syndrome. This is a chronic localised encephalitis with focal epileptic seizures causing progressive neurologic deficits and mental impairment. The etiology and the clinical features of the syndrome are discussed, and the diagnostic role of the new imaging modalities is emphasized. This is the first report about this entity in Hungary.

Topics: Acyclovir; Carbamazepine; Child, Preschool; Electroencephalography; Encephalitis; Epilepsies, Partial; Humans; Hungary; Intellectual Disability; Magnetic Resonance Imaging; Male; Phenytoin; Syndrome; Tomography, X-Ray Computed

Herpes Simplex Encephalitis (HSE) appears to be underdiagnosed in India, though viral encephalitides constitutes an important entity with significant morbidity. With an upsurge in AIDS, HSE may perhaps emerge as an important opportunistic infection in future. We discuss the clinical features and laboratory evaluation of nine cases of HSE seen in the last 12 years at our center. Diagnosis was established by brain biopsy in one, virological studies in six and at autopsy in three. Immunocytochemically viral antigens could be localized in 4 biopsied/autopsied brain tissue and in CSF cells on a cytospin preparation in one. This has facilitated rapid diagnosis in our cases. Virus isolation was successful in two. Three subjects were treated with acyclovir and all survived with variable morbidity. Four patients expired and none of them had received any specific antiviral drugs. Rapid diagnosis and early treatment with acyclovir has been highlighted.

Topics: Acyclovir; Adult; Biopsy; Brain; Electroencephalography; Encephalitis; Female; Herpes Simplex; Humans; Male; Middle Aged; Tomography, X-Ray Computed

To report the occurrence of vesicular lesions on the skin of a child receiving intravenous acyclovir therapy.. A 12-year-old boy with presumed herpes simplex encephalitis developed cutaneous vesicular lesions following intravenous acyclovir administration. The lesions were initially thought to be herpetic. Further evaluation of the vesicle fluid and the temporal relationship of the development of the lesions with acyclovir administration led to the conclusion that the reaction was drug induced.. Although inflammation and phlebitis are fairly common after acyclovir infusion, the development of vesicular lesions appears to be rare. Only two cases, both in adults, have been published in the medical literature. Although several theories have been proposed, including hypersensitivity, local drug toxicity, and tissue damage associated with extravasation, the mechanism of this reaction remains unclear.. Vesicular eruption is a rare adverse reaction in patients receiving acyclovir. Careful evaluation is necessary to differentiate this reaction from herpetic lesions.

Topics: Acyclovir; Catheterization, Peripheral; Child; Diagnosis, Differential; Drug Eruptions; Encephalitis; Herpes Simplex; Humans; Infusions, Intravenous; Male

Herpes simplex virus (HSV) may cause severe disease in neonates with high mortality and devastating sequelae. Adenine arabinoside (ara-A) and acyclovir can be effective in treating the neonatal disseminated disease, but optimal doses of the drugs are still debated.. The files of 12 neonates treated for HSV infection between May 1983 and April 1989 in 9 departments of pediatrics were studied. The following data were analysed: age at initial signs, clinical manifestations, CSF abnormalities, viral and immunological studies, imaging techniques used to detect brain damage, doses and duration of treatment.. The mean age at the first infectious signs was 12.3 +/- 9.3 days and neurological manifestations were first seen at 18.3 +/- 7.7 days. Acyclovir was given intravenously for 2 to 4 weeks at doses of 30 mg/kg/24 hr (5 patients) or 60 mg/kg/24 hr (7 patients) at an average of 7.7 days after the first clinical manifestations. The initial dose of 30 mg/kg/24 hr was increased to 50 or 60 mg/kg/24 hr in 3 patients. Five patients died during treatment, and 5 had severe sequelae; follow-up for the 2 remaining patients was not possible. There was no correlation between prognosis and the dose of acyclovir, which was well tolerated in all patients.. The best results are obtained when treatment is started early. This retrospective study failed to show any dose-dependent difference in the efficacy of acyclovir. A prospective study with different doses would be useful.

Topics: Acyclovir; Encephalitis; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Prognosis; Retrospective Studies

A 48-year-old male was admitted to our hospital because of fever, headache and vomiting. At admission, the level of consciousness was depressed (drowsy) with slight confusion. Extremely miotic pupils, nuchal stiffness, ataxia and myoclonic movements of both upper limbs were observed. The eye movements were almost normal and there was no definite limb weakness or sensory impairment. A few days after admission, his level of consciousness further decreased, and opsoclonus, ataxic breathing and intestinal paralysis appeared. The body temperature fluctuated remarkably ranging from 33.0 degrees C to 39.0 degrees C. The cerebrospinal fluid (CSF) examination revealed lymphocytic dominant pleocytosis, increase of protein and decrease of glucose. Enzyme-linked immunosorbent assay (ELISA) showed increased antibody (IgG) to herpes simplex virus (HSV) in both serum and CSF. The antibody in CSF further elevated at the later examination. Magnetic resonance imaging (MRI) demonstrated high signal intensity areas mainly in the cerebellum and sporadically in the supratentorial subcortical white matter on T2-weighted images. Administration of Gadolinium-DTPA also revealed an additional lesion in the pons. From these findings, he was diagnosed as herpetic encephalitis involving the brainstem and the cerebellum, and acyclovir was administered. Although his initial symptoms and signs started to recover three weeks after admission, he newly developed complete flaccid paraplegia, dysuria and sensory disturbance with the spinal cord level of the 4th thoracic segment. The oligoclonal IgG bands were detected in the cerebrospinal fluid of the convalescent stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans; Male; Middle Aged; Spinal Cord Diseases

Malignant gliomas are the most common malignant brain tumors and are almost universally fatal. A genetically engineered herpes simplex virus-1 mutant with decreased neurovirulence, dlsptk, has been shown to kill human glioma cells in culture and in animal models. However, intracranial inoculation of dlsptk is limited by fatal encephalitis at higher doses. Therefore, additional engineered and recombinant herpes simplex mutants with demonstrated reduced neurovirulence (AraAr9, AraAr13, RE6, R3616) were examined as antiglioma agents. One long-term human glioma cell line and two early-passage human gliomas in culture were destroyed by all four viruses tested. In a subcutaneous glioma model, AraAr13, RE6, and R3616 retained substantial antineoplastic effects in nude mice when compared with controls (one-sided Wilcoxon rank test, P < 0.05 for one or more doses each). When tested in a nude mouse intracranial glioma model, both RE6 and R3616 significantly prolonged average survival without producing premature encephalitic deaths at two doses (log-rank statistic, P < 0.007). Histopathological studies of the brains of surviving animals revealed minimal focal encephalitis in two of three RE6-treated animals and no evidence of encephalitis in either one of three RE6-treated or in three of three R3616-treated animals. No evidence of residual tumor was seen in four of the six surviving animals. Additionally, both RE6 and R3616 were found to be susceptible to the common antiherpetic agent acyclovir, adding to their safety as potential antiglioma agents. Recombinant and engineered viruses that minimize host toxicity and maximize tumoricidal activity merit further study as antineoplastic agents.

Topics: Acyclovir; Animals; Brain Neoplasms; Encephalitis; Female; Glioma; Herpes Simplex; Humans; Mice; Mice, Nude; Mutation; Neoplasm Transplantation; Simplexvirus; Transplantation, Heterologous; Tumor Cells, Cultured

Since Acyclovir is available a sufficient treatment of herpes simplex virus (HSV) encephalitis exists. Febrile convulsions may occur as the initial manifestation of an encephalitis, particularly of an HSV encephalitis. Within 25 months out of 151 children with febrile convulsions five children with complicated febrile convulsions were admitted at the pediatric department of Graz. In all children HSV antibodies in serum and cerebrospinal fluid (CSF) were negative and the diagnosis of an HSV encephalitis was made by positive CSF HSV polymerase chain reaction (PCR). Therefore, in any suspected case, i.e. in any case of a complicated febrile convulsion, CSF should be investigated including a HSV PCR to rapidly confirm or exclude HSV encephalitis.

Topics: Acyclovir; Cerebrospinal Fluid; Child, Preschool; Diagnosis, Differential; Encephalitis; Female; Fever; Humans; Infant; Magnetic Resonance Imaging; Male; Polymerase Chain Reaction; Seizures; Simplexvirus

All cases of neurological infections virologically verified as due to herpes simplex virus (HSV) during a 2-year period in the Helsinki University Hospital area were studied. Altogether 10 cases were divided clinically into two forms: encephalitis 5 cases, polyradiculomyelitis, meningitis and miscellaneous 5 cases. All the cases of encephalitis were treated with acyclovir. None of the severe cases of herpes radiculomyelitis received this drug, because of lack of a rapid virological diagnosis. Besides encephalitis HSV was associated with other types of severe diseases and those need attention for proper therapy.

Topics: Acyclovir; Adult; Aged; Blood-Brain Barrier; Cerebrospinal Fluid; Encephalitis; Female; Herpes Simplex; Humans; Male; Meningitis; Middle Aged; Myelitis; Polyradiculopathy; Simplexvirus

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans; Survival Rate; Vidarabine

A 16-year-old male diabetic patient presented with bilateral salivary gland swellings followed by encephalitis. The EEG did not show the characteristic periodic lateralising epileptic discharges. Neuro-imaging disclosed compromise of temporal and frontal lobes as well as brain stem which correlated well with his clinical deterioration. Serology and frontal brain biopsy were positive for herpes simplex virus while mumps titers were not significant. Despite delayed acyclovir therapy, the patient recovered enough to be discharged home with a permanent pseudobulbar palsy. Herpes simplex encephalitis involving zones other than temporal lobes is exceptional. To our knowledge, there are no reported cases of pseudobulbar palsy as a sequelae of HSV encephalitis.

Topics: Acyclovir; Adolescent; Biopsy; Brain; Brain Damage, Chronic; Diagnosis, Differential; Encephalitis; Follow-Up Studies; Herpes Simplex; Humans; Inclusion Bodies, Viral; Magnetic Resonance Imaging; Male; Microscopy, Electron; Mumps; Neurologic Examination

In-depth case study of a herpes simplex virus encephalitis patient who presents with a relatively clear knowledge disorder and anterograde amnesia in the absence of any other major cognitive deficit. The main neuropsychological feature is a category-specific impairment restricted to living things. The patient misnamed pictures of animals and vegetables, could not accurately draw animals from memory or verbally describe their visual appearance, and was not accurate in sorting pictures of real animals from pictures of unreal animals; conversely, in the same tasks her performance with artifactual objects was either errorless or superior to that with animals. We interpret the patient's category-specific deficit as due to a selective disturbance within the structural description system, rather than a deficit in low-level visual processing or semantic memory. From this case study and a review of other reported cases we claim that such deficit of form-knowledge is a consequence of the extensive lesions that affect bilaterally the inferior parts of the temporal lobes. The patient here described thus offers further empirical evidence for the crucial role of the inferotemporal cortex in processing visual knowledge about concepts.

Topics: Acyclovir; Encephalitis; Female; Herpes Simplex; Humans; Language; Memory; Mental Processes; Middle Aged; Perception; Tomography, X-Ray Computed; Visual Perception

Topics: Acyclovir; Encephalitis; Herpes Zoster; Humans; Immunocompromised Host

The polymerase chain reaction method was used to diagnose herpes simplex encephalitis in children. Initial samples of cerebrospinal fluid from 15 patients with herpes simplex encephalitis were all positive for the herpes simplex virus DNA by polymerase chain reaction assay. In terms of early diagnosis, polymerase chain reaction assay became positive significantly earlier than the detection of intrathecally produced anti-herpes simplex virus antibody using the enzyme-linked immunosorbent assay (4.4 vs 8.9 days after onset; P less than .01). Serial examinations showed that the presence of virus DNA in cerebrospinal fluid continued for 3 to 18 days after the neurologic onset (mean 10.1 days). Four of the 15 patients had a relapse of encephalitis after completing acyclovir therapy. The mean duration of initial acyclovir therapy in the recurrent group was significantly shorter than that in the nonrecurrent group. In recurring cases, herpes simplex virus DNA reappeared temporarily in the cerebrospinal fluid of two patients. These results show that polymerase chain reaction assay is a useful diagnostic tool for the early and noninvasive diagnosis of herpes simplex encephalitis in children. Results also suggest that a comparatively short duration of acyclovir therapy may be related to a relapse of herpes simplex encephalitis in some children.

Topics: Acyclovir; Child, Preschool; DNA, Viral; Encephalitis; Enzyme-Linked Immunosorbent Assay; Female; Herpes Simplex; Humans; Male; Polymerase Chain Reaction; Recurrence; Simplexvirus; Time Factors

Routine brain biopsy is often recommended in all patients suspected of having herpes simplex encephalitis (HSE). This approach is based upon the lack of ability to make the diagnosis of HSE on clinical grounds, the need to exclude other diseases for which there is specific therapy, and to stop empiric therapies. Acyclovir is a relatively safe, effective antiviral agent with little toxicity as currently used to treat HSE. Thus this is not a problem. Careful review of alternate diagnoses established at brain biopsy reveals few for which biopsy is the only and best way of making the diagnosis. Thus empiric therapy with acyclovir should be considered in some children in whom all appropriate diagnostic techniques fail to establish specifically treatable diseases. Early detection of HSV antigen in CSF may provide a non-invasive means of early diagnosis in the future.

Topics: Acyclovir; Adolescent; Adult; Antigens, Viral; Child; Child, Preschool; Encephalitis; Frontal Lobe; Herpes Simplex; Humans; Infant; Simplexvirus; Temporal Lobe

The authors relate the results of the use of virolex (acyclovir), a new etiotropic agent, for the treatment of some herpetic lesions of the nervous system. The use of the drug for the treatment of herpetic encephalitis, one of the gravest forms of encephalitides, exerts a beneficial effect. In the course of the treatment, it is of paramount importance to adhere to the established time of therapy, since the disease may recur. The treatment with virolex of different forms of herpes zoster in children and adults brings about positive results as well.

Topics: Acyclovir; Adolescent; Adult; Child; Child, Preschool; Encephalitis; Female; Herpes Simplex; Herpes Zoster; Humans; Male; Middle Aged; Recurrence; Time Factors

5 cases of acute herpes simplex encephalitis were verified by specific IgG antibodies in cerebrospinal fluid and serum among 31 cases with 'sporadic encephalitis' within one year. All were treated with acyclovir, 4 with remarkable response--2 cured and 2 significantly recovered, except one died due to delayed specific treatment. The dosage of acyclovir used by the author was 5mg/kg/12-24 hours.

Topics: Acyclovir; Adolescent; Adult; Antibodies, Viral; Encephalitis; Female; Herpes Simplex; Humans; Immunoglobulin G; Male; Middle Aged

We report a patient with encephalitis who showed anterograde and retrograde amnesia with MRI abnormalities localized in the bilateral amygdala (AM) and hippocampus (HIPP). A 25-year-old man suddenly experienced a generalized tonic-clonic seizure (GTCS). He was admitted because of increasing lethargy with two further GTCSs during the following 6 days. The patient had high fever, and neurological examination revealed somnolence, disorientation, amnesia, and nuchal stiffness. MRI revealed bilateral symmetrical abnormalities localized in the AM and HIPP, which showed low intensity on T1-weighted images and high intensity on T2-weighted images. Cerebrospinal fluid examination showed a mildly elevated cell count. We suspected herpes simplex virus type I encephalitis and began treatment with acyclovir. After the patient regained a clear consciousness, his antero- and retrograde amnesia continued for several months. The MRI abnormality became less distinct with the improvement of amnesia. We consider that the MRI abnormality was indicative of inflammation and edema, and that the lesion in the AM and HIPP had induced the amnesia.

Topics: Acyclovir; Adult; Amnesia; Amygdala; Encephalitis; Herpes Simplex; Hippocampus; Humans; Magnetic Resonance Imaging; Male

Topics: Acyclovir; Brain; DNA; Encephalitis; Female; Herpes Simplex; Humans; Male; Radiography

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans

Herpes zoster associated encephalitis is a very rare complication of herpes zoster. We are reporting a young healthy man who developed this complication along with the usual cutaneous presentation of herpes zoster. He was successfully treated with acyclovir.

Topics: Acyclovir; Adolescent; Encephalitis; Herpes Zoster; Humans; Incidence; India; Male

Topics: Acyclovir; Encephalitis; Humans; Virus Diseases

The authors provide the clinical and laboratory data on the etiological structure of acute viral encephalitides in children. Special attention is devoted to the description of the clinical picture of the gravest form of encephalitis caused by type I herpes simplex virus. Present the laboratory data on the long-term preservation of type I herpes simplex virus in the CNS, which correlates to the clinical and morphological findings of the subacute or recurrent course of the disease. Discuss the results of the treatment with the antiviral drug acyclovir (zovirax).

Topics: Acute Disease; Acyclovir; Antibodies, Viral; Cerebrospinal Fluid; Child; Child, Preschool; Encephalitis; Herpes Simplex; Humans; Infant; Recurrence; Simplexvirus

Herpes simplex encephalitis (HSE) carries a high mortality rate. Therefore, an early diagnosis and institution of acyclovir are essential. We report a case of biopsy-proven HSE with 2 negative cerebrospinal fluid (CSF) analyses and 2 normal CT scans. However, MRI together with EEG were abnormal early in the disease stressing their significant role in any suspected case of HSE. Although brain biopsy remains controversial, CSF herpes simplex antigen detection offers hope in providing an early or retrospective diagnosis while specific antiviral therapy with acyclovir is initiated. Overdependency on routine CSF analysis or head CT scan can result in unnecessary delays in diagnosis and treatment.

Topics: Acyclovir; Antibodies, Viral; Antigens, Viral; Biopsy; Brain; Electroencephalography; Encephalitis; Herpes Simplex; Humans; Magnetic Resonance Imaging; Middle Aged; Opportunistic Infections; Simplexvirus; Tomography, X-Ray Computed

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

Topics: Acyclovir; Antibodies, Viral; Antigens, Viral; Base Sequence; Brain Chemistry; DNA, Viral; Encephalitis; Evaluation Studies as Topic; Herpes Simplex; Humans; Immunoglobulin G; Molecular Sequence Data; Polymerase Chain Reaction; Simplexvirus

Two patients on dialysis because of chronic renal failure who developed herpes zoster associated encephalitis are reported. Both developed overt encephalopathy despite treatment with oral acyclovir for the preceding herpes zoster eruption. The encephalopathy responded rapidly to intravenous acyclovir.

Topics: Acyclovir; Administration, Oral; Aged; Encephalitis; Female; Herpes Zoster; Humans; Injections, Intravenous; Kidney Failure, Chronic; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory

Topics: Acyclovir; Aged; Combined Modality Therapy; Drug Therapy, Combination; Encephalitis; Herpes Zoster; Humans; Immunization, Passive; Male; Prednisolone

Topics: Acyclovir; Adolescent; Capsid; Encephalitis; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Male

Three children are described in whom herpes simplex encephalitis (HSE) followed a clearly biphasic course. The secondary deterioration may be due to a resurgence of the viral infection and calls into question the adequacy of current treatment regimens for HSE. Alternatively, a postinfectious neuroallergic process may be active in which case immunomodulatory treatment might be more appropriate than further antiviral treatment.

Topics: Acyclovir; Child; Dexamethasone; Encephalitis; Female; Herpes Simplex; Humans; Infant; Male; Recurrence

This is a report on diagnostic and therapeutic experience in 6 patients aged 3 weeks to 6.3 years suffering from herpes simplex encephalitis. In 2 patients, a 3-week-old newborn and a 1.3-year-old boy, acyclovir-therapy started at days 8 and 17 respectively, following the demonstration of hemorrhagic necrosis in the brain by cranial CT-scan and IgM-specific HSV-antibodies in the blood. A 6.3-year-old girl was treated with acyclovir at day 10 of her illness, when cCT showed hemorrhagic necrosis in the brain. It was not before the 21st day, that diagnosis of HSE could be confirmed serologically. She suffered a relapse of encephalitis 5 weeks later. In a 3-month-old boy, treated with acyclovir at day 4 of his illness, IgM-specific HSV-antibodies were found already at day 4. His clinical course was complicated by subdural effusion. These 4 children survived with severe neurologic sequelae. Another 2 patients, a 5- and 7.5-month-old boy respectively, survived without apparent defect. In both cases vesicles upon the tongue appeared in the beginning of illness. Acyclovir-therapy started at day 7, diagnosis being confirmed serologically later. In our experience HSE should be suspected in children suffering from fever, drowsiness and focal or secondarily generalizing seizures. In these cases antiviral therapy should not depend on serologic findings.

Topics: Acyclovir; Combined Modality Therapy; Diagnosis, Differential; Electroencephalography; Encephalitis; Evoked Potentials; Female; Follow-Up Studies; Herpes Simplex; Humans; Infant; Infant, Newborn; Male; Neurologic Examination; Tomography, X-Ray Computed

Two children, an eight-year-old girl and a seven-month-old boy, recovered from herpes simplex encephalitis with minimal neurological residua following acyclovir treatment. Subsequently, they experienced marked deterioration, interpreted as either recrudescent infection or a post-infectious phenomenon. Features of the deterioration included encephalopathy and hyperkinetic movement disorder. MRI studies showed extensive neocortical damage, without involvement of the basal ganglia, thalamus or subthalamic nuclei. With aggressive supportive care, both children made a slow, steady recovery over several months. This supportive care is best provided in a closely supervised interdisciplinary setting.

Topics: Acyclovir; Brain; Brain Damage, Chronic; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Encephalitis; Female; Follow-Up Studies; Herpes Simplex; Humans; Infant; Magnetic Resonance Imaging; Male; Neurocognitive Disorders; Neurologic Examination; Neuromuscular Diseases

Topics: Acyclovir; Antibodies, Viral; Biopsy; Brain; Encephalitis; Herpes Simplex; Humans; Simplexvirus

Two patients with presumed herpes simplex encephalitis developed severe non-oliguric acute renal failure shortly after acyclovir infusions. Renal function returned to normal in less than 3 weeks after discontinuation of acyclovir. Renal biopsies done during the acute phase demonstrated interstitial oedema, eosinophils and cellular aggregates in both and granulomata in the second case suggesting acyclovir-induced hypersensitivity interstitial nephritis.

Topics: Acyclovir; Adult; Encephalitis; Female; Humans; Male; Middle Aged; Nephritis, Interstitial

Acute encephalitis due to Epstein-Barr virus is described. The initial diagnosis was based on clinical features and a positive Monospot test. Early treatment with intravenous acyclovir was given; steroids were not used. The patient made a rapid and complete recovery from a comatose state. The effectiveness of acyclovir in this condition remains unproven but early treatment is recommended in severely ill patients whose prognosis is uncertain.

Topics: Acyclovir; Adolescent; Antibodies, Viral; Encephalitis; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Male; Penicillin G

1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (brovavir) and acyclovir were compared for their antiviral effects against herpes simplex virus type 1 (HSV-1) model infections in mice. Both drugs were not toxic to mice when they were administered orally by the same schedule used for therapeutic experiments. Brovavir was less toxic than acyclovir when injected by the intraperitoneal (i.p.) route. Marked efficacies of brovavir by either oral or i.p. administration were demonstrated in both experimental encephalitis and i.p. infection with HSV-1 WT-51 strain. Treatment with brovavir at a dose of 15 or 25 mg/kg twice daily resulted in increasing both survival rate and mean survival time of the infected mice. On the contrary, acyclovir showed only marginal effect against the experimental encephalitis. Survival rates of mice treated with brovavir were higher than those treated with acyclovir at corresponding doses with statistical significance. The superiority of brovavir was also found in the intracerebral infection with strain VR-3, a highly virulent strain for mice. Brovavir, but not acyclovir, at a dose of 200 mg/kg reduced the mortality. Acyclovir, however, were significantly effective in reducing mortality of systemically infected mice by both oral and i.p. administrations. The effective dose of acyclovir was lower than that of brovavir against i.p. infection with strain WT-51. Differences in mortality of strain VR-3-infected mice were statistically significant between acyclovir- and brovavir-treated groups.

Topics: Acyclovir; Animals; Antiviral Agents; Arabinofuranosyluracil; Disease Models, Animal; Drug Administration Routes; Encephalitis; Herpes Simplex; Humans; Male; Mice; Simplexvirus; Survival Rate

A 64 year-old woman experienced, at 6 weeks' interval, two episodes of encephalitis with left hemiparesis, coma and signs of meningitis. Paraclinical examinations showed lymphocytic meningitis, right temporal hypodensity at CT and high titers for herpes simplex at blood serology. The spontaneous course was favourable with almost complete recovery. A third recurrence took place 2 months later with left hemiplegia, confusion and meningism. A tentative diagnosis of herpes simplex encephalitis was confirmed by major intrathecal synthesis of herpes virus specific antibodies and by highly suggestive MRI images. Treatment with acyclovir resulted in rapid regression of motor deficit and meningism, but neuropsychological disorders regressed more slowly with persistent visuo-constructive and memory disorders. During a fourth and milder recurrence, a stereotactic temporal brain biopsy was performed, which showed lesions of encephalitis and elevated titers for HSV1 in the temporal fluid. Another course of acyclovir followed by vidarabine produced complete remission. The possibility of recurrent types of herpes simplex encephalitis is discussed.

Topics: Acyclovir; Coma; Encephalitis; Female; Hemiplegia; Herpes Simplex; Humans; Meningitis, Viral; Middle Aged; Recurrence; Serologic Tests; Stereotaxic Techniques; Vidarabine

Herpes simplex virus (HSV) is regarded as an agent that selectively affects temporal and frontal lobes with necrosis and hemorrhage, and no case of herpes simplex encephalitis (HSE) with white matter lesion in a diffuse fashion has previously been reported. A 2-year-old boy developed high fever, right hemi-convulsions and lethargy. Computed tomography (CT) showed wedge-shaped areas of high density in the left frontal region, whereas, cerebral angiography disclosed no vascular abnormality. T1-weighted magnetic resonance imaging (MRI) demonstrated cortical changes which were similar to those illustrated by CT. However, T2-weighted images depicted further spread high intensities of the lesion. The patient's symptoms spontaneously disappeared before an antiviral drug, acyclovir, was administered. After the significant increase of HSV antibody titers in serum and cerebro-spinal fluid (CSF) established a definite diagnosis, acyclovir was intravenously given at a daily dosage of 30 mg/kg for a period of 6 days in order to prevent the recurrence of HSE. Two months later, T2-weighted MRI visualized a diffuse lesion of increased signal intensities involving the white matter of both hemispheres, while both CSF protein and myelin basic protein were significantly elevated. Despite of these changes of the white matter, our patient developed a few symptoms such as mild speech disturbance, slight weakness of the right upper limb and sialorrhea. Although the mechanism of these changes in the white matter remains obscure, it is postulated that a direct invasion of HSV to the white matter, an immunological disorder following HSV infection and a side effect of acyclovir could have triggered a reversible process of demyelination of the cerebral white matter.

Topics: Acyclovir; Cerebral Cortex; Child, Preschool; Demyelinating Diseases; Encephalitis; Herpes Simplex; Humans; Magnetic Resonance Imaging; Male; Tomography, X-Ray Computed

A severe herpes simplex encephalitis with documented intra-cerebral lesions and brain edema was treated successfully with acyclovir and beta-interferon. The increase in intracranial pressure during the second week was well controlled by ICP monitoring. Life-threatening pressure peaks were avoided through the use of thiopental, osmodiuretics, TRIS, and lidocaine.

Topics: Acyclovir; Adult; Brain Damage, Chronic; Combined Modality Therapy; Encephalitis; Follow-Up Studies; Herpes Simplex; Humans; Interferon Type I; Intracranial Pressure; Male; Neurologic Examination

A 43-year-old homosexual man was hospitalized in April 1988 because of acute epigastric pain. It was known that he had had a HIV infection for a year, and in April 1988 it was defined as stage Walter Reed I. Acute, exudative, nonspecific pancreatitis was diagnosed. Three weeks later cerebral symptoms (disturbances of consciousness), hypoacusis, and impaired vision developed. The ocular fundus displayed areas of edema and whitish clouding in the retina, first in the left eye and later also in the right. These were initially assumed to be anemic infarctions until the differential diagnosis of acute retinal necrosis with possible herpesvirus infection was made. On the basis of ophthalmoscopic findings cytomegalovirus retinitis appeared improbable. Serologic examinations showed increased levels of IgG antibody titers of cytomegalovirus and herpes simplex virus (both 1:20,000). Therapy with intravenous infusions of Acyclovir was instituted (1500 mg/d). After a few days the patient regained consciousness as well as his hearing and vision. There was complete resolution of the retinal exudates. This excellent therapeutic result of Acyclovir therapy confirmed the diagnosis of acute retinal necrosis syndrome, identified the cerebral symptoms as herpes encephalitis, and explained the entire disease process as the first opportunistic infection in HIV infection, i.e., by that time the patient had developed stage Walter Reed 6 (AIDS). Problems of differential diagnosis and the therapeutic schedule with Acyclovir are discussed.

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Acyclovir; Adult; Encephalitis; Herpes Simplex; Humans; Male; Ophthalmoscopy; Pancreatitis; Referral and Consultation; Retinal Necrosis Syndrome, Acute

Survival from untreated herpes simplex type 1 encephalitis is well known to be accompanied by severe cognitive impairments. Recently, acyclovir has been proven to be the most effective available treatment for this disease, with the expectation that it would appreciably reduce morbidity. We performed detailed assessments of four consecutive patients who received acyclovir in the early stages of biopsy-proven herpes encephalitis and who now have been followed up for 1.5 to 4 years. All four patients showed definite residual on either clinical or formal neuropsychological testing, most commonly dysnomia and impaired new learning for both verbal and visual material, even though three had normal performance on a standard clinical mental status test. All four patients were unable to function at their prior level of achievement. Therefore, despite early administration of acyclovir in herpes encephalitis, long-lasting neuropsychological residua are likely. Furthermore, cognitive deficits of prognostic importance may not be detected by clinical screening.

Topics: Acyclovir; Adult; Cognition; Encephalitis; Female; Herpes Simplex; Humans; Male; Middle Aged; Neuropsychological Tests

Topics: Acyclovir; Adult; Drug Administration Schedule; Encephalitis; Herpes Simplex; Humans; Infant, Newborn; Injections, Intravenous

Topics: Acute Kidney Injury; Acyclovir; Encephalitis; Herpes Simplex; Humans; Infusions, Intravenous; Male; Middle Aged

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Animals; Drug Resistance, Microbial; Encephalitis; Herpes Simplex; Humans; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Simplexvirus; Thymidine Kinase; Virulence

Topics: Acyclovir; Antibodies, Viral; Drug Therapy, Combination; Encephalitis; Herpes Simplex; Humans; Serologic Tests; Simplexvirus; Vidarabine

A 6 year old child is described with infection due to herpes simplex virus type 1 causing brain stem encephalitis. The diagnosis was established by enzyme immunosorbent assays of the cerebrospinal fluid and serum which demonstrated antibody responses to herpes simplex virus. Recovery occurred and the importance of early use of acyclovir in achieving a good outcome is emphasized.

Topics: Acyclovir; Antibodies, Viral; Brain Stem; Child; Encephalitis; Enzyme-Linked Immunosorbent Assay; Herpes Simplex; Humans; Male; Simplexvirus; Time Factors

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

The use of Acyclovir and early diagnosis greatly affect prognosis of the disease and a case that pathognomonically points to this need is reported.

Topics: Acyclovir; Electroencephalography; Encephalitis; Female; Herpes Simplex; Humans; Middle Aged; Prognosis; Time Factors; Tomography, X-Ray Computed

A retrospective study of outcome in 57 herpes simplex encephalitis (HSE) patients treated between 1960 and 1987 is reported. HSE was confirmed by virus isolation or detection of intrathecal anti HSV synthesis. 24 patients did not receive antiviral therapy, 19 were vidarabine recipients and 14 were treated with acyclovir. Mortality was not correlated with sex or age but with the level of consciousness at onset of therapy. Acyclovir therapy was by far superior to vidarabine with respect both to mortality and neurologic sequelae after a mean follow-up period of 170 days.

Topics: Acyclovir; Adolescent; Adult; Aged; Child; Encephalitis; Female; Follow-Up Studies; Herpes Simplex; Humans; Interferon Type I; Male; Middle Aged; Vidarabine

The article is reviewing various diagnostic and treatment techniques in encephalitis caused by the virus of herpes simplex. Clinical symptoms and variants of the course of the disease are considered together with laboratory investigations of cerebrospinal fluid, electroencephalography and computerized tomography. The patients with the herpetic encephalitis suspected, need intensive treatment measures. Besides the conventional techniques, the early use of Acyclovir is recommended.

Topics: Acyclovir; Diagnosis, Differential; Electroencephalography; Encephalitis; Herpes Simplex; Humans; Tomography, X-Ray Computed

Topics: Acyclovir; Adult; Child; Drug Therapy, Combination; Encephalitis; Female; Humans; Interferons; Male; Middle Aged; Vidarabine; Virus Diseases

A 43-year-old man with the acquired immunodeficiency syndrome had clinical evidence of multifocal disease of the brain, but computed tomography was negative. Magnetic resonance imaging revealed multifocal lesions, histologically proven to be caused by cytomegalovirus. Therapy with 9[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (BW B759U) resulted in stabilization of the patient's clinical disease and radiographic improvement of the lesions.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Encephalitis; Ganciclovir; Humans; Magnetic Resonance Imaging; Male

Among the many different manifestations of Epstein-Barr virus (EBV) infection, neurologic disturbances are less frequently observed, and they are diverse in nature. A young woman was admitted with acute hyperthermia, mydriasis, nystagmus, respiratory insufficiency, muscular hypertonia, evolving to decerebrate posturing, and bilateral facial epileptic contractions. The appearance of atypical blood lymphocytes, hepatitis, migrating skin rash, positive heterophile antibody tests, and specific serologic tests for EBV led to a diagnosis of EBV encephalitis. Under treatment with intravenously administered acyclovir, the patient recuperated almost completely. This case illustrates a less frequent manifestation of EBV infection.

Topics: Acyclovir; Adult; Coma; Encephalitis; Female; Herpesvirus 4, Human; Humans; Infectious Mononucleosis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adrenal Gland Diseases; Antiviral Agents; Chorioretinitis; Cytomegalovirus Infections; Encephalitis; Ganciclovir; Gastrointestinal Diseases; Humans; Pneumonia, Viral

Topics: Acyclovir; Adolescent; Adrenal Cortex Hormones; Chickenpox; Child; Child, Preschool; Encephalitis; Female; Humans; Male

Of 33 patients with viral encephalitis, four (three women, one man) succumbed to the disease. Of the surviving patients, 23 were followed for a median interval of 4 years after discharge. A considerable residual syndrome could be detected in two cases only. The outcome was determined by identification of causative organism (especially herpes simplex virus), initial consciousness disturbances and pleocytosis in the cerebrospinal fluid. On the other hand, the age of the patients, electroencephalographic findings and a symptomatic epilepsy played no major role. Without confirmed virus findings, immunoglobulins were as effective as the virostatic therapy regimens; with identification of causative organism, combined treatment with acyclovir and immunoglobulins was most effective.

Topics: Acyclovir; Adult; Aged; Antibodies, Viral; Encephalitis; Female; Humans; Male; Mental Disorders; Middle Aged; Prognosis; Retrospective Studies; Time Factors; Tomography, X-Ray Computed; Virus Diseases

Since antiviral chemotherapy is available herpes encephalitis has become of great importance among viral affections of the central nervous system. Five young infants are presented with special problems of this disease and its diagnostic possibilities especially serological and imaging methods (CT scan, nuclear magnetic resonance tomography, ultrasonography of the brain) as well as electroencephalography. Clinical symptoms are very important since all those methods are not sufficient for early diagnosis and prompt onset of antiviral chemotherapy. Herpes encephalitis should be considered after apparent febrile seizures with focal symptoms as well as increasing disturbance of consciousness as manifestation of acute encephalopathy.

Topics: Acyclovir; Brain; Brain Damage, Chronic; Electroencephalography; Encephalitis; Female; Herpes Simplex; Humans; Infant; Magnetic Resonance Imaging; Male

The clinical course of herpes zoster associated encephalitis (HZAE) with special emphasis on the treatment with acyclovir is described from the experience in 14 own patients and 47 review cases. Immunosuppression and dissemination involved increased risk of HZAE, whereas cranial zoster implied no or only a slightly increased risk. The symptoms were mainly disturbances of mental function and ataxia. Nuchal rigidity was noted in approximately one third of cases. The median duration from dermatomal lesion to HZAE was 15 days in immunosuppressed patients versus 5 days in non-immunosuppressed patients. Abnormal spinal fluid findings included mononuclear pleocytosis, occasionally with low glucose concentration. Protein was elevated in half of the patients. Serum sodium levels were often low. Brain CAT scans were generally normal and EEGs always abnormal. Recurrence of HZAE was noted in 2 patients. Treatment with acyclovir seemed to have a beneficial effect. The results, however, need cautious interpretation due to the heterogenous patient material. Two patients developed signs of HZAE while on treatment with desciclovir but recovered during ongoing therapy.

Topics: Acyclovir; Aged; Encephalitis; Female; Herpes Zoster; Humans; Immune Tolerance; Male; Middle Aged; Time Factors

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans; Recurrence; Vidarabine

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans; Male; Middle Aged; Time Factors

The clinical features, investigative profiles and outcome of 46 patients with biopsy or autopsy-proven herpes simplex encephalitis admitted to the Institute of Neurological Sciences, Glasgow between 1962 and 1985 were analysed retrospectively. The protean presenting symptoms and signs included a history of a prodromal influenza-like illness (48 per cent), rapid onset of headache, clouding of consciousness and confusion (52 per cent), meningism (65 per cent), raised intracranial pressure (33 per cent), deep coma (35 per cent), mutism or aphasia (46 per cent), focal neurological signs (89 per cent), and seizures (61 per cent). When seizures occurred they were almost always focal. The electroencephalogram was the most useful diagnostic test being abnormal in all cases, the majority showing focal changes in one or other hemisphere. Of the neuroradiological procedures employed, computerized tomographic and isotope brain scanning most frequently demonstrated localizing abnormalities in one or both temporal and/or frontal lobes. Midline shift was seen in half the cases. The cerebrospinal fluid was abnormal in every case but was not diagnostic. Cerebral biopsy of one temporal lobe was performed in 40 cases and a positive diagnosis of acute necrotizing encephalitis was made in 37 of these. Herpes simplex virus was isolated from the brains of 29 of the 40 cases in which the procedure was attempted, but immunofluorescence assays for antigens to herpes simplex virus were only positive in 11 out of 25 cases. Serological assays showed a greater than four-fold rise in the anti-herpes simplex virus antibody titre in 13 out of 22 patients tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acyclovir; Adolescent; Adult; Aged; Child; Child, Preschool; Encephalitis; Female; Herpes Simplex; Humans; Idoxuridine; Infant; Male; Middle Aged; Retrospective Studies; Scotland; Vidarabine

Herpes simplex encephalitis is the most common cause of sporadic encephalitis in the western world. Patients usually have altered levels of consciousness, altered levels of mentation, fever, headache, and personality changes. These may progress to hemiparesis and seizures. Exact diagnosis must be established by brain biopsy and identification of the virus in biopsy material. There is a great need for a noninvasive test that is positive early in the disease. Without antiviral treatment the mortality rate is greater than 70%, and many survivors have serious disabilities. Both adenine arabinoside and acyclovir decrease death and morbidity, but acyclovir is the preferred drug. With acyclovir about 40% of patients will survive with normal development or minor levels of impairment but more than half of the patients will die or suffer significant impairment. It is essential to treat early; patients who are young and have not reached coma or impaired consciousness may show 65% recovery and return to normal function. Development of new antiviral drugs or other types of therapies is desirable. Herpetic skin lesions are likely to be more confusing than diagnostic because other types of encephalitis with fever often precipitate recurrent herpes that is unrelated to the encephalitis.

Topics: Acyclovir; Adult; Encephalitis; Female; Herpes Simplex; Humans; Male; Middle Aged; Vidarabine

Acyclovir sodium is the drug of choice for the treatment of herpes simplex encephalitis. We treated an immunocompetent patient with a ten-day course of intravenous acyclovir sodium at the recommended dosage of 10 mg/kg every eight hours for clinically apparent herpes simplex encephalitis. After marked improvement, his condition deteriorated four days after completing acyclovir therapy. A subsequent brain biopsy specimen disclosed acyclovir-sensitive herpes simplex virus type 1. A longer duration of acyclovir therapy (14 to 21 days) should be considered for treating herpes simplex encephalitis.

Topics: Acyclovir; Aged; Brain; Drug Administration Schedule; Encephalitis; Herpes Simplex; Humans; Male; Recurrence; Tomography, X-Ray Computed

Both viral meningitis and encephalitis in infants and children give clinical features of various severity. The mechanism of viral encephalitis varies from CNS cellular destruction, immune or oedematous process. The clinical and EEG features of herpes encephalitis in the child are usually well recognizable. CSF characteristics are important for differential diagnosis. Management therapy includes anti-oedema treatment, prevention or cure of seizures. Passive immunisation against rubella, rubeola and measles is the best prevention therapy for post-infectious encephalitis. Herpes encephalitis prognosis has improved with acyclovir therapy. In France, mortality due to post-infectious encephalitis is estimated below 5% and sequellae below 20%.

Topics: Acute Disease; Acyclovir; Adolescent; Child, Preschool; Diagnosis, Differential; Encephalitis; Herpesviridae Infections; Humans; Infant; Meningitis, Viral; Meningoencephalitis; Prognosis

The sensitivity of different herpes simplex virus type 2 (HSV-2) strains to inhibition by 5-vinyl-1-beta-D-arabinofuranosyluracil (VaraU) was evaluated in comparison to 9-(2-hydroxyethoxymethyl)guanine (ACV; acyclovir) and trisodiumphosphonoformate (Na3PFA; foscarnet), using a plaque inhibition assay in primary rabbit testes (PRT) cells as well as in human embryonic lung fibroblast (HELF) cell cultures. The order of decreasing activity found was ACV much greater than VaraU greater than Na3PFA in PRT cells and ACV greater than VaraU much greater than Na3PFA in HELF cells, with 50% inhibition doses (ID50) of 1.8, 8.8, and greater than 110 microM for the three drugs in HELF cells, respectively. After 72hr of drug treatment, inhibition of HELF cell proliferation by VaraU (ID50, greater than 1000 microM) was less than that by ACV and Na3PFA, resulting in high selectivity indexes of greater than 100 against HSV-2 for VaraU and ACV. Their in vivo efficacy was assessed in a mouse encephalitis model. Using a treatment schedule of three daily intraperitoneal (ip) doses over a period of 5 days, only the survival times of mice were considerably prolonged by VaraU (150 or 300 mg/kg per day; P less than 0.05 or P less than 0.001, respectively). In contrast, ACV treatment (150 mg/kg per day) led to a nearly complete prevention of encephalitis and death (P less than 0.001). Similar therapy results with VaraU application through the drinking water were obtained using only one-sixth of the high ip dose (approximately 50 mg/kg per day) but over a prolonged period of treatment. Under similar conditions no therapeutic effect of oral Na3PFA was observed.

Topics: Acyclovir; Animals; Antiviral Agents; Arabinofuranosyluracil; Cells, Cultured; Encephalitis; Female; Foscarnet; Herpes Simplex; Mice; Organophosphorus Compounds; Phosphonoacetic Acid; Simplexvirus; Uridine; Virus Replication

Topics: Acyclovir; Encephalitis; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Herpesvirus 4, Human; Humans

The protected nucleoside 1-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-beta-D-arabinofuranosyl)-5-ethylura cil (10) was prepared by condensation of 3,5-dibenzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide (9) with 2,4-bis-O-(trimethylsilyl)-5-ethyluracil (8). The ratio in this coupling reaction has been raised to 17:1 in favor of the desired beta-anomer. Deprotection by aminolysis gave 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-ethyluracil (FEAU, 1) in 67% isolated yield from the bromo sugar 9. In vitro data show that FEAU has activity against herpes simplex virus types 1 and 2 comparable to that of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-methyluracil (FMAU, 2), 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU, 3), and acyclovir (ACV, 12). The cellular toxicity of FEAU was found to be much lower than that of the other nucleoside analogues. Biochemical experiments indicate that FEAU has similar affinity toward thymidine kinases encoded by HSV 1 and 2 and a much lower affinity for cellular thymidine kinase than thymidine. The in vivo antiviral effects of FEAU, FMAU, FIAU, and ACV were evaluated against herpes infection in a systemic mouse encephalitis model and a cutaneous guinea pig model. While FEAU showed activity comparable to that of ACV in the systemic infection model, it was superior in the cutaneous herpes infection model.

Topics: Acyclovir; Animals; Arabinofuranosyluracil; Cell Line; Chemical Phenomena; Chemistry; Encephalitis; Female; Guinea Pigs; Herpes Simplex; Mice; Simplexvirus; Skin Diseases; Thymidine Kinase; Uridine

For the electroencephalographer, focal temporal periodic complexes have been strongly associated with herpes simplex virus encephalitis (HSVE). The appearance and subsequent disappearance of these complexes has generally been held to herald a poor prognosis. This report involves an elderly man with HSVE who survived with no neurologic deficits despite the presence and later disappearance of periodic sharp complexes. This supports the view that the periodic complexes are more a function of the pathophysiologic changes caused by HSVE as opposed to a marker of tissue injury.

Topics: Acyclovir; Aged; Electroencephalography; Encephalitis; Epilepsies, Partial; Evoked Potentials; Herpes Simplex; Humans; Male

Topics: Acyclovir; Adult; Aged; Encephalitis; Female; Herpes Zoster; Humans; Male

Herpes simplex encephalitis may be underdiagnosed in Britain. We report eight patients treated at one hospital over three years. Fever, impaired consciousness or focal neurological signs were seen in all patients at presentation but herpes simplex encephalitis was rarely considered as the initial diagnosis. The electroencephalogram was the only initial investigation that was abnormal in each case and was the most useful test in establishing a clinical diagnosis. The diagnosis was confirmed by laboratory methods in each case. Following acyclovir treatment five patients were able to resume normal activities, one patient has moderate disability and two patients died. Three patients showed clinical evidence of relapse but two improved after further treatment with acyclovir. Herpes simplex encephalitis is a treatable condition and should be considered in all patients presenting with fever and neurological signs. The electroencephalogram is usually abnormal and the changes may be characteristic of the condition.

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans; Tomography, X-Ray Computed

Topics: Acyclovir; Aged; Encephalitis; Female; Herpes Zoster; Humans; Immune Tolerance; Male; Middle Aged; Opportunistic Infections

Topics: Acyclovir; Aged; Biopsy; Brain; Encephalitis; Herpes Simplex; Humans; Male; Middle Aged

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

Topics: Acyclovir; Brain; Encephalitis; Female; Herpes Simplex; Humans; Infant; Recurrence

Topics: Acyclovir; Encephalitis; Humans; Polyuria

Topics: Acyclovir; Biopsy; Brain; Encephalitis; Herpes Simplex; Humans

Topics: Acyclovir; Biopsy; Brain; Encephalitis; Herpes Simplex; Humans

Topics: Acyclovir; Biopsy; Brain; Encephalitis; Herpes Simplex; Humans

We report a case of herpes simplex encephalitis (HSE) with initial coma and severe left-sided hemiparesis in which combined treatment with adenine arabinoside and acyclovir was followed by complete recovery. This favorable result is discussed in view of the literature of HSE treatment including experimental studies on antiviral activity of both drugs. Combined treatment may be useful in severe cases of HSE.

Topics: Acyclovir; Adult; Drug Therapy, Combination; Encephalitis; Female; Herpes Simplex; Humans; Tomography, X-Ray Computed; Vidarabine

Topics: Acyclovir; Adult; Drug Administration Schedule; Encephalitis; Female; Herpes Simplex; Humans; Recurrence

Topics: Acyclovir; Adult; Encephalitis; Herpes Simplex; Humans; Kidney; Male

Topics: Acyclovir; Adult; Biopsy; Brain; Child; Child, Preschool; Diagnosis, Differential; Encephalitis; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Recurrence; Vidarabine

A previously healthy patient became acutely encephalopathic, with complete disorientation and amnesia, several days after the onset of thoracic herpes zoster. She had transiently abnormal electroencephalographic results, abnormalities on radionuclide brain scanning, and cerebrospinal fluid pleocytosis. There was no evidence of a toxic/metabolic encephalopathy except for a mildly elevated ammonia level. Intravenously administered acyclovir (30 mg/kg per day) induced a dramatic response, with complete resolution of the encephalopathy within 72 hours and normalization of the electroencephalographic results. The scant clinical experience with the successful use of acyclovir in the treatment of herpes zoster-associated encephalitis is reviewed.

Topics: Acyclovir; Drug Evaluation; Electroencephalography; Encephalitis; Female; Herpes Zoster; Humans; Middle Aged

Problems and developments of antiviral chemotherapy can be demonstrated with herpes encephalitis: optimum medical intensive care and early acyclovir therapy reduce lethality from approx. 70% to approx. 20% and also the rate of sequelae in surviving patients. Evaluation of interferon therapy is not possible at present. In newborns of mothers with manifestations of genital herpes very early therapy (prophylaxis) should be possible and instituted.

Topics: Acyclovir; Antiviral Agents; Encephalitis; Herpes Simplex; Herpesviridae Infections; Humans; Infant, Newborn; Interferons; Vidarabine

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans; Injections, Intravenous; Prognosis; Vidarabine

The efficiency of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BrVaraU, VaraU) as inhibitors of three herpes simplex virus type 1 (HSV-1) strains was assessed in comparison to (E)-5-(2-bromovinyl)-2'-deoxyuridine (BrVUdR), 9-(2-hydroxyethoxymethyl)guanine (ACV), and trisodium phosphonoformate (Na3PFA) using a plaque assay in human embryonic lung fibroblast (HELF) cell cultures. The following order of decreasing activity was found: BrVaraU greater than VaraU greater than BrVU-dR greater than ACV much greater than Na3PFA. In HELF cell cultures, the selectivity indexes of VaraU and BrVaraU were 10 times higher than those of BrVUdR and ACV. Protection of mice from encephalitis and death due to intracerebral (i.c.) infection with a clinical HSV-1 isolate was nearly complete if mice were treated intraperitoneally (i.p.) with two daily doses of VaraU and BrVaraU (100 or 200 mg/kg per day) over a period of 5 or 10 days. The efficacy was similar to ACV, but, using a treatment schedule of three daily i.p. doses over 10 days, with equimolar amounts of the nucleoside analogs, VaraU and BrVaraU (140 and 180 mg/kg per day) were superior to ACV (130 mg/kg per day) (P less than 0.05).

Topics: Acyclovir; Animals; Arabinofuranosyluracil; Bromodeoxyuridine; Cells, Cultured; Encephalitis; Female; Foscarnet; Herpes Simplex; Humans; Mice; Phosphonoacetic Acid; Simplexvirus; Uridine; Viral Plaque Assay

Topics: Acyclovir; Adult; Encephalitis; Female; Herpesviridae Infections; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Infectious; Respiratory Distress Syndrome, Newborn

Three herpes simplex virus mutants that contain drug resistance mutations in the DNA polymerase gene exhibited no significant reduction in replication in the ears of mice compared with the wild type after inoculation at that site but were attenuated for pathogenicity after intracerebral inoculation. Cataracts were common sequelae in mice that survived mutant infections.

Topics: Acyclovir; Animals; Cataract; Cytarabine; DNA-Directed DNA Polymerase; Drug Resistance; Encephalitis; Exodeoxyribonucleases; Female; Herpes Simplex; Mice; Mice, Inbred BALB C; Simplexvirus; Viral Proteins

Topics: Acyclovir; Aged; Encephalitis; Female; Herpes Zoster; Humans

Topics: Acyclovir; Encephalitis; Female; Herpes Simplex; Humans; Middle Aged

Two cases are reported of severe encephalitis in infants that were caused by a primary infection with herpes simplex virus type 1. Both patients presented with focal seizures; the clinical diagnosis was confirmed by the rapid appearance of IgM antibody to herpes simplex virus type 1 in cerebrospinal fluid and serum. In spite of the early use of acyclovir, which was administered by the intravenous route, the clinical response was poor and both infants were left with severe neurological impairment.

Topics: Acyclovir; Encephalitis; Female; Herpes Simplex; Humans; Immunoglobulin M; Infant

Five paediatric cases of herpes simplex virus encephalitis are described. In each case the diagnosis was made with some difficulty. A high index of suspicion is required in order that appropriate diagnostic and therapeutic manoeuvres are initiated at an early stage of the illness.

Topics: Acyclovir; Brain; Child; Child, Preschool; Encephalitis; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Male; Tomography, X-Ray Computed

A gravid woman with herpes Type II encephalitis delivered an infant with herpes neonatorum despite therapy with acyclovir. Acyclovir was not measurable in the baby's serum 10 h after birth. The viral isolate was sensitive to acyclovir in vitro, and the neonatal infection responded to treatment with the drug. Prenatal antiviral therapy may be ineffective in preventing intrauterine herpesvirus infection.

Topics: Acyclovir; Adult; Cesarean Section; Encephalitis; Female; Herpes Simplex; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Serologic Tests; Time Factors; Vidarabine

The synthesis of the thio analogue (thio-DHPG, 2) of 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG, 1) is described. The synthesis of 2 proceeded via the condensation of acetoxymethyl sulfide 9 with diacetylguanine 10 to give the protected nucleoside analogue 11. Although catalytic hydrogenolysis failed, the benzyl ether functionalities of 11 were successfully cleaved by an acetolysis reaction to furnish 14. Ammonolysis of 14 gave 2, which was also transformed to sulfoxide 15 and sulfone 16. Preliminary in vitro screening indicated that 2 exhibited comparable activity to DHPG against herpes simplex virus type 1 (HSV-1) but was less active against the type 2 virus (HSV-2) and human cytomegalovirus (HCMV). In a mouse encephalitis model (HSV-2), subcutaneous treatment with 2 led to a 53% reduction in mortality at a dose of 100 mg/kg per day.

Topics: Acyclovir; Animals; Chemical Phenomena; Chemistry; Cytomegalovirus; Drug Evaluation, Preclinical; Encephalitis; Female; Ganciclovir; Herpes Simplex; Mice; Simplexvirus

Methoxymethyldeoxyuridine (MMUdR) when used in combination with either trifluorothymidine (F3TdR) or phosphonoformate (PFA) showed synergistic activity against herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) in vitro, whereas MMUdR and acycloguanosine (ACG) combination was antagonistic against herpes viruses. HSV-1 mutants resistant to ACG, arabinofuranosyladenine (Ara-A), MMUdR or PFA were isolated. Drug-resistant HSV-1 virus mutants were analyzed for cross sensitivity to ACG, Ara-A, F3TdR, MMUdR, MMUdR-5'-monophosphate (MMUdR-MP) and PFA. The Ara-A-resistant (Ara-AR) virus exhibited 3-fold resistance to MMUdR-MP (ID50 = 105 microM). The ACG-resistant (ACGR) mutant was 160-fold less sensitive to MMUdR (ID50 greater than 1138 microM). The MMUdR-resistant (MMUdRR) mutant remained sensitive to all other antiviral drugs in vitro. Ara-A provided protection against HSV-1 encephalitis in immunosuppressed mice inoculated with a low dose (200 PFU/mouse) of MMUdRR virus or wild-type HSV-1. F3TdR decreased incorporation of tritiated deoxyuridine [( 3H]UdR) in RK-13 cells by 50% at 0.068 microM. Under similar conditions, MMUdR (up to 600 microM) and PFA (up to 208 microM) were without effect on incorporation of [3H]UdR into DNA. In combination chemotherapy experiments, MMUdR (up to 300 microM) used along with F3TdR (up to 1.08 microM) neither decreased nor enhanced cytotoxicity of F3TdR as measured by incorporation of [3H]UdR into cellular DNA. Similarly, MMUdR (up to 300 microM) in combination with PFA (up to 166 microM) was nontoxic to host cells.

Topics: Acyclovir; Animals; Antiviral Agents; Deoxyuridine; DNA, Viral; Drug Combinations; Drug Resistance, Microbial; Drug Synergism; Encephalitis; Foscarnet; Herpes Simplex; Male; Mice; Organophosphorus Compounds; Phosphonoacetic Acid; Rabbits; Simplexvirus; Thymidine; Trifluridine; Vidarabine; Virus Replication

The case of a 67 year old male who developed severe encephalitis associated with herpes zoster ophthalmicus is described. Encephalitis occurred in the absence of cutaneous dissemination and recovery followed treatment with Acyclovir.

Topics: Acyclovir; Aged; Antibodies, Viral; Encephalitis; Herpes Zoster; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Male

The antiherpes virus activities of acyclovir and its close analogue 3-[(2-hydroxy-1-hydroxymethylethoxy)methyl]guanine (BWB759U) were compared in vitro and in vivo. The activities of both compounds against herpes simplex virus and varicella-zoster virus were similar in the majority of cell lines. However, in mouse-derived and HeLa cells, BSB759U was more effective than acyclovir against herpes simplex virus. Mutants of herpes simplex virus deficient in thymidine kinase and resistant to acyclovir were found to vary in their sensitivity to BWB759U. In two mouse models of herpes simplex virus infection BWB759U was more effective than acyclovir.

Topics: Acyclovir; Animals; Cell Line; Disease Models, Animal; Dose-Response Relationship, Drug; Encephalitis; Ganciclovir; HeLa Cells; Herpes Simplex; Herpesvirus 3, Human; Humans; Mice; Mice, Inbred BALB C; Simplexvirus; Time Factors; Viral Plaque Assay

9-(1,3-Dihydroxy-2-propoxymethyl)guanine (DHPG), was evaluated in cell culture and in animals for its inhibitory effect on herpes simplex viruses. Compounds run for comparison included acyclovir, 2'-fluoro-2'-deoxy-5-iodo-arabinofuranosylcytosine (FIAC), and 2'-fluoro-2'-deoxy-5-methyl-arabinofuranosyluracil (FMAU). In plaque reduction assays DHPG, acyclovir, FIAC, and FMAU were inhibitory to six herpes types 1 and 2 virus strains at concentrations of 0.2-2.4 microM. These concentrations were much lower than those required to inhibit Vero cell proliferation. In guinea pig vaginal infections, DHPG provided significantly greater inhibition of herpetic lesions than did acyclovir. In a herpes type 2 infection model in mice, DHPG, and FMAU were active at 5 mg/kg, whereas acyclovir and FIAC showed no statistically significant effect at 80 mg/kg. In a herpes type 1 encephalitis model, DHPG and FMAU were active at doses less than 10 mg/kg, with FMAU being about 4 times more potent than DHPG in that model.

Topics: Acyclovir; Animals; Antiviral Agents; Arabinofuranosyluracil; Brain Diseases; Cell Line; Chlorocebus aethiops; Cytarabine; Encephalitis; Female; Ganciclovir; Guinea Pigs; Herpes Genitalis; Herpes Simplex; Kidney; Mice; Simplexvirus; Structure-Activity Relationship

Primary varicella-zoster virus infection (chickenpox) in immunocompromised children is frequently associated with visceral dissemination and attendant high mortality. Eight children with malignant neoplasms and chickenpox with visceral involvement (seven with hepatitis, three with pneumonitis, two with encephalitis, and two with coagulopathy) were initially treated with intravenously (IV) administered vidarabine but demonstrated progressive visceral involvement. After three days of vidarabine treatment (two days for two patients), seven had rising serum SGPT levels, all eight had pneumonitis, seven had deteriorating mental status and/or seizure activity, and six had worsening coagulopathy. Vidarabine was replaced by IV administered acyclovir, with subsequent improvement in all but the most severely ill patient who died. Seven of eight patients recovered completely; no side effects of acyclovir were observed. This clinical experience suggests that acyclovir may be more effective than vidarabine in disseminated varicella infection; however, controlled clinical trials will be necessary to establish this.

Topics: Acyclovir; Blood Coagulation Disorders; Chickenpox; Child; Encephalitis; Female; Hepatitis, Viral, Human; Humans; Leukemia, Lymphoid; Lymphatic Diseases; Male; Pneumonia, Viral; Vidarabine

Four patients with typical manifestations of herpes simplex encephalitis were treated with Aciclovir. Infection with herpes simplex virus was confirmed in three of the four cases. Complete cure was achieved in each of the patients despite severe initial disease patterns. In view of these results in the treatment of a disease that had so far been partly lethal or produced severely defective states, the specific use of Aciclovir is emphasised.

Topics: Acyclovir; Adult; Cell Transformation, Viral; Cerebrospinal Fluid; Electroencephalography; Encephalitis; Epilepsy, Tonic-Clonic; Female; Herpes Simplex; Humans; Male; Middle Aged; Status Epilepticus

Toxoplasmosis encephalitis developed in three male homosexuals with AIDS. Clinical symptoms of encephalitis began with a nonspecific organic mental syndrome. In two cases there developed late focal symptoms. There were light to moderately severe generalized EEG changes with additional focal signs. CSF findings and toxoplasmosis titres were not diagnostically altered. Computed tomography demonstrated multiple areas of decreased density in cortex and cerebellum. Administration of pyrimethamine and sulfamethoxydiazine to the three patients brought about clinical improvement within a few days and regression of abnormal CT changes within a few weeks of onset of treatment. One patient died after an encephalitis recurrence: autopsy demonstrated toxoplasma pseudocysts in immediate proximity to small necrotic foci in the brain. The possibility of toxoplasma encephalitis should be considered in AIDS patients who develop an organic mental syndrome. Often the diagnosis can only be made after response to a trial of toxoplasmosis treatment.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Candidiasis, Oral; Electroencephalography; Encephalitis; Homosexuality; Humans; Ketoconazole; Male; Tomography, X-Ray Computed; Toxoplasmosis

Topics: Acyclovir; Adult; Encephalitis; Female; Herpes Zoster; Humans; Infusions, Parenteral

A case of herpes zoster encephalitis which responded very rapidly to acyclovir is presented. The differential serum: cerebrospinal fluid antibody response was followed and its value in making the diagnosis is discussed. The penetration of acyclovir into the cerebrospinal fluid was measured, and found to be in agreement with predicted values.

Topics: Acyclovir; Adult; Encephalitis; Female; Herpes Zoster; Humans

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans; Male; Middle Aged

Topics: Acyclovir; Brain Stem; Encephalitis; Female; Herpes Simplex; Humans; Middle Aged

Topics: Acyclovir; Bone Marrow Transplantation; Drug Administration Schedule; Drug Resistance, Microbial; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Herpesviridae; Herpesviridae Infections; Humans; Injections, Intravenous; Male; Recurrence

Topics: Acyclovir; Antiviral Agents; Chronic Disease; Drug Therapy, Combination; Encephalitis; Female; Hepatitis B; Herpes Simplex; Humans; Infant, Newborn; Interferons; Male; Nucleic Acid Synthesis Inhibitors; Simplexvirus; Vidarabine

Motor lesions following herpes zoster are quite common. Hemiparesis, paraparesis, pareses of the facial and other cranial nerves as well as segmental pareses can be observed. We report on a patient suffering from zoster ophthalmicus complicated by paresis of the third cranial nerve. As a cause, a partial brain stem-encephalitis was diagnosed. The patient recovered after antiviral treatment (Aciclovir, Inosiplex).

Topics: Acyclovir; Brain Stem; Encephalitis; Herpes Zoster Ophthalmicus; Humans; Inosine Pranobex; Male; Middle Aged; Ophthalmoplegia

Mice with established herpes encephalitis were used to compare the effects of chemotherapy using three different nucleoside analogues. Encephalitis was produced by intranasal inoculation of a type 1 strain of herpes simplex virus. Without chemotherapy all mice died within 5 to 7 days of inoculation. Oral acyclovir (ACV) was a successful preventative measure if commenced within 2 days of inoculation but much less effective if the onset of treatment was further delayed. From the third day, when central nervous system infection had definitely become established, ACV only reduced mortality if given intraperitoneally (i.p.) at regular 6-hourly intervals. Comparison with bromovinyldeoxyuridine (BVdU) and the new nucleoside analogue dihydroxypropoxymethylguanine (DHPG) using the same 6-hourly i.p. regimen revealed that BVdU was poorly effective, despite better activity in vitro, whereas DHPG was the most successful. Virus was rapidly eradicated from all parts of the brain by DHPG therapy, and by day 10, no infectious virus remained in the brains of treated mice, no virus antigens were observed and no trace of virus DNA could be detected in neural tissues by Southern blotting.

Topics: Acyclovir; Animals; Antiviral Agents; Brain; Bromodeoxyuridine; Encephalitis; Female; Ganciclovir; Herpes Simplex; Mice; Mice, Inbred BALB C; Simplexvirus; Time Factors; Trigeminal Ganglion; Virus Replication

Topics: Acyclovir; Cytopathogenic Effect, Viral; Drug Resistance, Microbial; Electroencephalography; Encephalitis; Herpes Simplex; Humans; Mutation; Simplexvirus; Vidarabine; Virus Cultivation

Six cases of severe encephalitis due to measles, varicellae, mononucleosis, influenza, rubella and pertussis were treated with high doses of barbiturates in combination with steroids and artificial hyperventilation. Four of the patients also received antiviral therapy. They all survived without neurological sequelae. The use of barbiturates in high doses may be of importance for an improved outcome in patients with severe encephalitis.

Topics: Acyclovir; Adult; Chickenpox; Child; Combined Modality Therapy; Dexamethasone; Encephalitis; Female; Humans; Infant; Infectious Mononucleosis; Influenza, Human; Male; Measles; Middle Aged; Phenobarbital; Respiration, Artificial; Whooping Cough

Topics: Acute Disease; Acyclovir; Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow; Encephalitis; Erythropoiesis; Herpes Simplex; Humans

Topics: Acyclovir; Antiviral Agents; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpesviridae Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Keratoconjunctivitis; Male; Skin Diseases, Infectious; Vidarabine

Acyclovir is a new and well tolerated anti-viral agent whose role in the treatment of herpes simplex encephalitis (HSE) is still being evaluated. Although relapse of adenosine arabinoside treated HSE has been documented, this paper describes the recurrence of encephalitis after treatment with the recommended course of Acyclovir. A more extended course of Acyclovir produced a rapid and sustained improvement with minimal residual neurological deficit. We emphasise the need for more prolonged treatment and an awareness of the possibility of relapse when using Acyclovir for HSE.

Topics: Acyclovir; Adult; Electroencephalography; Encephalitis; Evoked Potentials; Herpes Simplex; Humans; Male; Recurrence; Tomography, X-Ray Computed

The therapeutic effectiveness of two new antiviral agents, 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodocytosine and 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)thymine, was compared with that of acyclovir and vidarabine. In mice inoculated intracerebrally with high 50% lethal doses of herpes simplex virus type 2, nontoxic intraperitoneal or oral treatments with the two new fluorinated antiviral agents were highly effective in reducing mortality. The two drugs were also effective when treatment was begun as late as 48 h after virus inoculation. The relative order of potencies of the drugs when compared on a molar basis or in terms of therapeutic index was 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)thymine much greater than 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodocytosine greater than vidarabine approximately to acyclovir. The new pyrimidine analogs were also found to lack immunosuppressive activity in mice. The combination of 1-(2-fluoro-2-deoxy-beta-=D-arabinofuranosyl)-5-iodocytosine and vidarabine was the most effective; significantly greater reduction in mortality was achieved with this combination than with either drug alone. Thirty minutes after intraperitoneal treatment with the fluorinated analogs, the drugs (or their metabolites) were transported to the brains of virus-inoculated and normal mice at levels about one-third to two thirds those in the blood. The levels of 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)thymine in the blood or brain were consistently higher than those found with equivalent intraperitoneal doses of the 5-iodocytosine analog.

Topics: Acyclovir; Administration, Oral; Animals; Antiviral Agents; Arabinofuranosyluracil; Brain; Cytarabine; Drug Therapy, Combination; Encephalitis; Female; Herpes Simplex; Injections, Intraperitoneal; Mice; Uridine; Vidarabine

Topics: Acyclovir; Adult; Child; Encephalitis; Herpes Simplex; Humans; Vidarabine

The advent of acyclovir has accentuated the problem of diagnosis and particularly the need for brain biopsy in patients with suspected herpes simplex encephalitis. U.S.A. and U.K. practices are contrasted and the current U.K. study of acyclovir in herpes simplex encephalitis is mentioned in which retrospective and relatively non-invasive methods of diagnosis are employed.

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans

Topics: Acyclovir; Adult; Dementia; Encephalitis; Female; Herpes Simplex; Humans; Quality of Life

Acyclovir (ACV) has been shown to inhibit the replication of herpes simplex virus (HSV) in vitro. We examined a wide variety of HSV clinical isolates for the presence of naturally occurring ACV-resistant (ACVr) variants. Although the ACV doses that inhibited 50% of these isolates were within the range of doses inhibiting 50% of the ACV-susceptible wild-type strains, we successfully isolated variants resistant to high ACV concentrations (25 to 75 microM) from each virion population even in the absence of prior drug exposure. Furthermore, we demonstrated, by fluctuation analysis of two encephalitis strains, that the ACVr variants were clonally distributed in the virus populations before exposure to ACV and did not result from rapid adaptation to ACV. All variants isolated after a single exposure to a high dose of ACV were true ACVr variants, as demonstrated by their plating efficiencies in the presence of ACV. We found that 36 and 50% of the ACVr variants of the two strains examined in detail displayed plating efficiencies in phosphonoacetic acid of greater than 0.1, possibly indicating that many of the ACVr variants contained alterations in the DNA polymerase gene locus. Because the distribution of ACVr variants in natural populations is relatively high (10(-4), these results suggest that selection of ACVr strains during ACV therapy is possible.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Microbial; Encephalitis; Herpes Simplex; Humans; Simplexvirus; Viral Plaque Assay

Topics: Acyclovir; Animals; Antiviral Agents; Creutzfeldt-Jakob Syndrome; Demyelinating Diseases; Encephalitis; Encephalomyelitis; Guanine; Herpes Simplex; Humans; Nervous System Diseases; Polyradiculoneuropathy; Reye Syndrome; Vidarabine; Virus Diseases

The effect of oral or intraperitoneal administration of acyclovir was evaluated in four experimental models of herpes simplex virus (HSV) encephalitis in mice. Mice were inoculated with HSV-1 or HSV-2 intracerebrally or with HSV-2 intranasally, intraperitoneally, or intravaginally. With all four routes of inoculation, oral acyclovir therapy significantly reduced mortality when started as late as 72 to 96 hours after viral challenge. Intraperitoneal acyclovir was not effective in protecting mice inoculated intravaginally, but was effective if given 24 to 48 hours after intracerebral or intranasal challenge and as late as 96 hours after intraperitoneal infection. Oral acyclovir was more active than intraperitoneal treatment in all four model infections. Levels of acyclovir inhibitory for HSV in cell culture were maintained in plasma and brain tissue throughout oral treatment but lasted only three to six hours after each intraperitoneal treatment. These results suggest that acyclovir may be useful in treating serious HSV infections in humans.

Topics: Acyclovir; Administration, Oral; Animals; Antiviral Agents; Brain; Encephalitis; Female; Guanine; Herpes Simplex; Injections, Intraperitoneal; Mice; Time Factors; Tissue Distribution

Animal models of cutaneous herpes simplex and herpetic encephalitis were used to demonstrate the antiviral potential of acyclovir. Of the various topical formulations of acyclovir tested against herpes simplex in guinea pigs, 5 percent acyclovir in modified aqueous cream was the most effective. Propylene glycol was included in this preparation to increase the aqueous solubility of acyclovir. Acyclovir and vidarabine were found to be equally effective against herpetic encephalitis in mice when administered either orally or subcutaneously at 100 mg/kg.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Animals; Antiviral Agents; Drug Evaluation, Preclinical; Encephalitis; Female; Guanine; Guinea Pigs; Herpes Simplex; Injections, Subcutaneous; Mice

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans; Immunity

Topics: Acyclovir; Antiviral Agents; Encephalitis; Guanine; Herpes Simplex; Humans

Topics: Acyclovir; Animals; Antibodies, Viral; Antiviral Agents; Encephalitis; Guanine; Herpes Simplex; Humans; Immunoglobulins; Mice