acyclovir and Nervous-System-Diseases

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

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

Topics: Acyclovir; Antiviral Agents; Humans; Japan; Magnetic Resonance Imaging; Nervous System Diseases; Serologic Tests; Vidarabine; Virus Diseases

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

With the decline in prevalence of childhood-acquired oral-labial herpes simplex type 1 infections in some populations and the increasing incidence of genital herpes infections in adults, clinicians are more likely to see patients with severe primary, first-episode genital herpes infections. Complications of these primary infections may include aseptic meningitis and urine retention secondary to sacral radiculopathy or autonomic dysfunction. Presented are the clinical course of first-episode and recurrent infections, complications, diagnostic laboratory methods, and results of controlled clinical trials evaluating the efficacy of topical, intravenous, and oral preparations of acyclovir.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Adult; Antibodies, Viral; DNA, Viral; Drug Resistance, Microbial; Female; Herpes Genitalis; Humans; Immunologic Deficiency Syndromes; Injections, Intravenous; Male; Nervous System Diseases; Proctitis; Prostatitis; Recurrence; Sex Factors; Sexually Transmitted Diseases; Urethral Diseases

Glial fibrillary acidic protein (GFAp) was analysed in cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and healthy controls. Patients with relapsing-remitting course (n = 13) were followed with quantitative neurological examinations and lumbar punctures during a 24-month period. The patient group was a subsample from a randomised, double-blind clinical trial of acyclovir on MS: 7 patients were treated with acyclovir and 6 were placebo controls. CSF was also collected from 5 age-matched healthy individuals with normal quantitative neurological examinations. The CSF assays disclosed increased concentrations of GFAp in MS patients compared to controls (p < 0.01). Furthermore, the GFAp levels correlated significantly with the deficit score (p < 0.01) but not with exacerbation frequency. When the group treated with acyclovir was compared with the placebo group, no significant change of CSF GFAp was observed. In the present study we show that GFAp is increased in CSF of patients with MS and that the levels correlate with the neurological dysfunction. Further work is needed to ascertain whether determinations of CSF GFAp can be used to monitor disease progression in MS or whether the assay may be useful to evaluate therapeutic intervention.

Topics: Acyclovir; Adult; Antiviral Agents; Double-Blind Method; Glial Fibrillary Acidic Protein; Herpesviridae Infections; Humans; Multiple Sclerosis; Nervous System Diseases; Spinal Puncture

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

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

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Ceftriaxone; Diagnosis, Differential; Encephalomyelitis, Eastern Equine; Fever; Humans; Infant; Male; Nervous System Diseases; Seizures

Topics: Acyclovir; Aged; Antiviral Agents; Electroencephalography; Herpes Zoster; Humans; Male; Nervous System Diseases

Topics: Acute Kidney Injury; Acyclovir; Aged; Attitude to Death; Delusions; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Herpes Zoster; Humans; Myoclonus; Nervous System Diseases; Neuropsychological Tests; Renal Dialysis; Risk Assessment

HaNDL (transient headache and neurological deficits with cerebrospinal fluid lymphocytosis) syndrome is an infrequent condition included at group 7 "headache attributed to non-vascular intracranial disorder" in the recent International Classification of Headache Disorders (ICHD-3), code 7.3.5. The description states "migraine-like headache episodes (typically 1-12) accompanied by neurological deficits including hemiparaesthesia, hemiparesis and/or dysphasia, but positive visual symptoms only uncommonly, lasting several hours. There is lymphocytic pleocytosis. The disorder resolves spontaneously within 3 months". In this description confusional state is not considered as a main symptom, even if in the literature this aspect is frequently reported. Here, we report the cases of two young boys presenting with confusional state as the main complaint. The possible pathogenesis of the different clinical presentation is discussed.

Topics: Acyclovir; Adolescent; Ceftriaxone; Confusion; Headache; Humans; Lymphocytosis; Male; Nervous System Diseases; Young Adult

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

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

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

Topics: Acyclovir; Humans; Kidney Failure, Chronic; Nervous System Diseases; Prodrugs

Recent studies utilizing an ex vivo mouse model of herpes simplex virus (HSV) reactivation have led to the hypothesis that, under physiologic conditions inducing viral reactivation, the immune cells within the infected ganglion block the viral replication cycle and maintain the viral genome in a latent state. One prediction from the ex vivo study is that reactivation in ganglia in vivo would be inhibited at early times postinoculation, when the numbers of inflammatory cells in the ganglia are greatest. To distinguish between an effect of the immune infiltrates on (i) infectious virus produced and/or recovered in the ganglion and (ii) the number of neurons undergoing lytic transcriptional activity (reactivating), an assay to quantify the number of neurons expressing lytic viral protein in ganglia in vivo was developed. Infectious virus and HSV protein-positive neurons were quantified from days 9 through 240 postinoculation in latently infected trigeminal ganglia before and at 22 h after hyperthermic-stress-induced reactivation. Significant increases in the amount of virus and the number of positive neurons were detected poststress in ganglia at all times examined. Unexpectedly, the greatest levels of reactivation occurred at the times examined most proximal to inoculation. Acyclovir was utilized to stop residual acute-phase virus production, and this treatment did not reduce the level of reactivation on day 14. Thus, the virus measured after induction was a product of reactivation. These data indicate that, in contrast to observations in the ex vivo model, immune cells in the ganglia during the resolution of acute infection do not inhibit reactivation of the virus in ganglia in vivo.

Topics: Acyclovir; Animals; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Male; Mice; Nervous System Diseases; Time Factors; Trigeminal Ganglion; Viral Proteins; Virus Activation; Virus Replication

To report a case of neurotoxicity and aseptic meningitis in a patient receiving valacyclovir.. An 86-year-old white man had started valacyclovir 1 g 3 times a day for a herpetic rash along the left side of his face. He subsequently presented with balance difficulties, constant frontal headaches, and a seizure 1 day prior to admission. Cerebral spinal fluid (CSF) analysis revealed 162 white cells/mm(3), 1 red blood cell/mm(3), glucose 56 mg/dL, and protein 144 mg/dL, with a negative Gram stain. Further laboratory examination failed to demonstrate other causes for the patient's clinical picture. After discontinuation of valacyclovir and supportive care, the patient symptomatically improved.. As of the third week of September 2003, only 1 other case of valacyclovir-related aseptic meningitis was published describing a patient with characteristics similar to those of our patient. Our patient's neurologic symptoms may have been due to acyclovir toxicity, but acyclovir-toxic patients present with normal CSF findings. Several drug classes, including nonsteroidal antiinflammatory drugs, antibiotics, and intravenous immunoglobulins, can induce aseptic meningitis. Other reasons for the patient's symptoms or causes of meningitis were excluded, although viral meningitis remains a possibility. Valacyclovir-induced aseptic meningitis was considered to be possible according to the Naranjo probability scale.. Healthcare providers should be aware of valacyclovir as a possible cause of drug-induced aseptic meningitis.

Topics: Acyclovir; Aged; Aged, 80 and over; Humans; Male; Meningitis, Aseptic; Nervous System Diseases; Valacyclovir; Valine

We reviewed 58 cases of varicella-zoster infection that occurred between 1988 and 1998 in 47 pediatric solid-organ transplant recipients. The median age of patients at the time of admission with varicella-zoster infection was 8.0 yr (range 1-17 yr). The median interval between transplantation (Tx) and varicella-zoster virus (VZV) infection was 1.6 yr (range 0.06-9.3 yr). Varicella infection occurred at a rate of one case for every seven transplant recipients. Among the 58 cases of VZV infection, 53% were varicella while 47% were herpes-zoster. Varicella infection occurred despite treatment with varicella-zoster immune globulin (VZIG) in 17 of 31 cases of varicella infection. However, the disease was generally mild with severe disease occurring in only two patients. One patient (1.7%) died as a result of bacterial sepsis. There was no significant relationship between VZV infection and specific immune suppressants. Episodes of rejection were more likely to be temporally associated with the occurence of herpes zoster than with varicella infection (p = 0.02). The data generated provide useful background information in our population in the prevaricella vaccine era.

Topics: Acyclovir; Adolescent; Antiviral Agents; Chickenpox; Chickenpox Vaccine; Child; Child, Preschool; Female; Graft Rejection; Herpes Zoster; Hospitals; Humans; Infant; Male; Nervous System Diseases; Organ Transplantation; Prevalence

Topics: Acyclovir; Antiviral Agents; Female; Herpes Zoster; Humans; Kidney Failure, Chronic; Middle Aged; Nervous System Diseases; Renal Dialysis

The authors report toxicity caused by valacyclovir in a patient on hemodialysis. After initial recuperation resulting from treatment with hemodialysis, the patient experienced a relapse of neurologic symptoms, again necessitating hemodialysis. Although acyclovir and its analogues are generally safe drugs, they should be used with caution in patients with end-stage renal disease. Therapeutic drug monitoring may be indicated.

Topics: Acyclovir; Antiviral Agents; Humans; Male; Middle Aged; Nervous System Diseases; Renal Dialysis; Valacyclovir; Valine

A 5-year-old girl with a kidney transplant developed post-transplant Epstein-Barr virus-induced lymphoproliferative disease. She was treated with acyclovir, alpha-interferon, and gamma globulin. A transplant nephrectomy was performed on day 4 due to acute rejection and she was started on hemodialysis. The acyclovir dose was decreased at this time. However, 6 days following the start of acyclovir she developed progressively worsening neurological symptoms resulting in a coma on day 8. Fourteen days after acyclovir was begun pre- and post-dose serum concentrations were 7.02 microM and 182.5 microM, respectively. Acyclovir was then discontinued and 2 days later the child's neurological status began to improve. We conclude that acyclovir in children with end-stage renal failure may lead to severe and reversible neurotoxicity, despite acyclovir dosage adjustment based on renal impairment.

Topics: Acyclovir; Antiviral Agents; Child, Preschool; Female; Humans; Kidney Transplantation; Lymphoproliferative Disorders; Nervous System Diseases; Postoperative Complications; Renal Dialysis

Three hundred and one patients with acute herpes zoster treated early with oral acyclovir were enrolled in an open, prospective study designed to evaluate painful and neurologic disorders over a 6-month period. Age, initial pain severity, and occurrence of a neurologic deficit influenced the incidence of postherpetic neuralgia. No relationship was found between initial rash severity and either pain incidence or neurologic deficit.

Topics: Acyclovir; Administration, Oral; Aged; Herpes Zoster; Humans; Middle Aged; Nervous System Diseases; Pain; Prospective Studies

Topics: Acyclovir; Administration, Oral; Female; Humans; Male; Middle Aged; Nervous System Diseases; Renal Dialysis

Severe neurotoxicity and acute renal failure developed in a patient with newly diagnosed AIDS while receiving high-dosage intravenous acyclovir for disseminated herpes zoster. Hemodialysis resulted in a rapid resolution of neurologic symptoms and was associated with a reduction in plasma acyclovir concentration. Acute hemodialysis therapy should be considered in cases of serious neurotoxicity secondary to acyclovir, especially when accompanied by renal failure.

Topics: Acquired Immunodeficiency Syndrome; Acute Kidney Injury; Acyclovir; Humans; Male; Middle Aged; Nervous System Diseases; Neurotoxins; Renal Dialysis

Topics: Acyclovir; Administration, Oral; Aged; Humans; Male; Nervous System Diseases

Topics: Acyclovir; Aged; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nervous System Diseases; Peritoneal Dialysis, Continuous Ambulatory; Radioimmunoassay

Topics: Acyclovir; Aged; Female; Humans; Kidney Failure, Chronic; Nervous System Diseases

The herpesvirus DNA polymerase inhibitor foscarnet, applied topically, and the anti-herpesvirus guanosine analogue buciclovir, given orally, decreased virus replication and disease development in primary skin infections of mice caused by herpes simplex virus type 1 (HSV-1). If the same tissues were infected via sensory nerves, following zosteriform spread of the virus the same treatments showed strongly decreased efficacy, or were inefficacious, when started before development of clinical signs in the infected tissues. These results were obtained in murine models of zosteriform spread of HSV-1 to the ear (following inoculation of the ventral side of the neck) or to the lower flank (following inoculation of the upper flank). In these models the immune system played a dominant role in virus clearance. The topically applied foscarnet could not prevent disease development in these models of recrudescent disease even when applied before the virus was detected in the skin, but a decrease in virus titre was obtained. Orally administered buciclovir lost efficacy when administered at the time of virus entry into the skin, i.e. 1 or 2 days before development of clinical signs. In the flank model, measuring lesion development, orally administered acyclovir also had a strongly decreased efficacy, when compared with its effect during infections in which lesion development did not involve translocation of virus through nerves. In the presence of developing immunity the inhibitors could not accelerate the clearance of virus from infected tissues. Furthermore, all treatments (topical foscarnet and oral buciclovir or acyclovir) were without effect on disease development when treatment was initiated on appearance of the first clinical signs of disease. As disease development following zosteriform spread of HSV resembles that in recurrent herpes in humans, and as the limited efficacy of the inhibitors observed resembles the poor results obtained with inhibitors of herpesvirus DNA synthesis in clinical studies on the treatment of symptomatic recurrent herpes, we suggest the use of animal models of zosteriform spread for pre-clinical evaluation of new antiherpes drugs.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Animals; Antiviral Agents; Disease Models, Animal; DNA Replication; DNA, Viral; Foscarnet; Herpes Simplex; Male; Mice; Nervous System Diseases; Organophosphorus Compounds; Phosphonoacetic Acid; Recurrence; Simplexvirus; Skin; Skin Diseases, Infectious; Virus Replication

On the basis of observation that acyclovir potentiates the in-vitro antiviral activity of 3-azido-2',3'-dideoxythymidine (also known as azidothymidine or zidovudine) against human immunodeficiency virus (HIV), we administered a regimen of azidothymidine and acyclovir to eight patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. An oral regimen of 100 mg of azidothymidine and 800 mg of acyclovir every 4 hours was in general well tolerated, with the principal toxicity being megaloblastic erythroid changes. The pharmacokinetics of the two drugs were independent of each other. Six patients received the drug combination for at least 10 weeks; all had increased numbers of T4+ lymphocytes (P = 0.028), and two of three assessable patients had reversal of anergy. Two patients tested positive for serum HIV p24 antigen at entry, but became negative with treatment. Data for this small group suggest that this drug combination can be tolerated in patients with severe HIV infections; this study can be used as a basis for larger studies of this drug combination.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Complex; Antiviral Agents; Drug Interactions; Drug Therapy, Combination; Hematologic Diseases; Humans; Male; Middle Aged; Nervous System Diseases; Pilot Projects; T-Lymphocytes, Helper-Inducer; Thymidine; Zidovudine

Patients who are homosexual, intravenous drug abusers, or have received multiple blood transfusions are at greater risk to contract the immunosuppressive disorders of acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). These persons also have a greater chance of developing serious neurologic complications after an episode of Herpes zoster. We present two cases which emphasize the serious complications of Herpes zoster ophthalmicus in such patients. Since systemically administered acyclovir may shorten the disease course and reduce the complications of Herpes zoster in immunocompromised individuals, the authors favor treatment of all such patients who have Herpes zoster ophthalmicus with a seven-day course of high-dose (30 mg/kg/day) intravenous acyclovir. To minimize serious neurologic complications in such patients, treatment should be instituted immediately before the results of human immunodeficiency virus (HIV) testing are known.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Complex; Female; Herpes Zoster Ophthalmicus; Humans; Injections, Intravenous; Male; Middle Aged; Nervous System Diseases; Risk Factors

Topics: Acyclovir; Adolescent; Female; Humans; Nervous System; Nervous System Diseases

Ninety-three Chinese patients with cutaneous herpes zoster were seen during a 4-year period. Thoracic zoster occurred most commonly, followed by ophthalmic, cervical and lumbosacral zoster. Neurological complications were present in eleven patients (11.8%), the commonest being Ramsay-Hunt syndrome and segmental limb paresis. The clinical picture, pathogenesis, treatment and outcome of segmental limb paresis, myelitis and delayed contralateral hemiparesis following zoster ophthalmicus are discussed. Nine immunocompromised patients received intravenous adenine arabinoside (vidarabine) or acycloguanosine (acyclovir), and no cutaneous or visceral spread occurred in these patients.

Topics: Acyclovir; Adolescent; Adult; Aged; Facial Paralysis; Female; Herpes Zoster; Humans; Male; Middle Aged; Nervous System Diseases; Prognosis; Retrospective Studies; Steroids; Tomography, X-Ray Computed; Vidarabine

The vast majority of the more than 300,000 annual cases of herpes zoster in the United States occur among healthy, immunocompetent persons. Most patients recover from reactivated varicella-zoster infection, but some experience complications. The most common of these is postherpetic neuralgia, but other neurologic as well as ocular and dermatologic complications can occur as well. Zoster during pregnancy is not of serious concern. Ongoing trials of antiviral agents are aimed at resolving the infection quickly and decreasing the incidence and severity of postherpetic neuralgia.

Topics: Acyclovir; Adenosine Monophosphate; Eye Diseases; Female; Herpes Zoster; Humans; Immunocompetence; Nervous System Diseases; Pregnancy; Skin Diseases, Infectious

Topics: Acyclovir; Drug Interactions; Humans; Kidney Diseases; Male; Meperidine; Middle Aged; Nervous System Diseases

The neuritic uptake and transport of three antiviral drugs were studied in a cell culture system with dissociated cells of rat dorsal root ganglia. Cultured sensory neurons extended neuritic projections which penetrated a vacuum grease sealed diffusion barrier in the culture. The peripheral infection with herpes simplex virus (HSV) type 1 (McIntyre) resulted in uptake and transport of HSV by neuritic extensions causing a neuronal infection inside the diffusion barrier. By varying the route of administration and concentration of drug and by manipulating the nerve cell culture system, neuritic uptake and transport also of the antiviral drugs (acyclovir, adenine-arabinoside and foscarnet) were demonstrable. The findings are discussed in relation to axonal transport and antiviral treatment of HSV infections of the nervous system.

Topics: Acyclovir; Animals; Antigens, Viral; Biological Transport; Cells, Cultured; Female; Foscarnet; Ganglia, Spinal; Herpes Simplex; Nervous System Diseases; Neurons; Organophosphorus Compounds; Phosphonoacetic Acid; Pregnancy; Rats; Rats, Inbred Strains; Vidarabine; Virus Replication

Six marrow transplant recipients receiving acyclovir at various dosages for herpesvirus infections developed neurologic symptoms during treatment. Three were receiving concomitant human alpha interferon, and all six had received previous intrathecal methotrexate. Symptoms developed a median of 8 days (range, 2 to 18 days) after initiation of therapy and consisted of lethargy or agitation in five patients, tremor in five, and disorientation or transient hemiparesthesias in one patient each. The only consistent laboratory finding was an abnormal electroencephalogram. Five patients had an increased myelin basic protein level in cerebrospinal fluid. Improvement or resolution of symptoms occurred a median of 13 days (range, 4 to 15 days) after cessation of acyclovir therapy. Acyclovir used at a wide range of dosages may be associated with reversible neurologic symptoms in patients after marrow transplantation. The contribution of previous prophylaxis for central nervous system leukemia, herpesvirus infections, marrow transplantation, or the concomitant use of interferon is unknown.

Topics: Acyclovir; Adolescent; Adult; Akathisia, Drug-Induced; Bone Marrow Transplantation; Child; Electroencephalography; Female; Herpesviridae Infections; Humans; Male; Nervous System Diseases; Paresthesia; Postoperative Complications; Tremor

Thirteen recipients of bone marrow transplants were given high-dose acyclovir and alpha-interferon (Cantell interferon) for the treatment of biopsy-proven cytomegaloviral pneumonia. Three patients survived. Doses of acyclovir between 500 and 1,000 mg/m2 of body surface area (peak plasma levels, 7-86 micrograms/ml) and doses of interferon between 2 X 10(4) and 40 X 10(4) units/kg per day (peak serum levels, 5-608 units/ml) were given. No consistent antiviral effect was seen despite the large doses employed. Possible marrow toxicity associated with this regimen occurred in five patients, neurologic symptoms in two, and nephrotoxicity in one. Thus, treatment with high-dose acyclovir plus alpha-interferon was moderately toxic but ineffective against cytomegaloviral pneumonia after bone marrow transplantation.

Topics: Acyclovir; Bone Marrow Transplantation; Combined Modality Therapy; Cytomegalovirus Infections; Humans; Interferon Type I; Kidney Diseases; Nervous System Diseases; Pneumonia, Viral

The antiviral drug, acyclovir, was tested on experimentally infected guinea pigs with either of two herpes simplex virus type 1 (HSV-1) isolates following intravaginal inoculation. The drug was continuously infused subcutaneously utilizing an osmotic pump. Infusion was begun either prior to virus inoculation (prophylactic) or after virus inoculation at the time of first appearance of lesions (therapeutic). Prophylactic treatment markedly reduced the severity of the genital lesions, the appearance of acute neurologic sequellae, and the virus excretion in the genital tract of guinea pigs infected with either of the two strains tested. Therapeutic acyclovir treatment, however, did not decrease the incidence of acute neurologic sequellae with one of the two HSV-1 strains tested, nor did it reduce the severity of the genital lesions of either strain. These neurologic sequellae may be due to insufficient levels of ACV in the central nervous system as the concentration of ACV in the dorsal root ganglia was found to exceed that of the plasma, but only trace amounts of acyclovir were present in the brain and spinal cord. Continuous perfusion of ACV gave far higher tissue levels than intermittent injections. These findings suggest that prophylactic ACV is far more effective than therapeutic treatment for genital herpes in the guinea pig model.

Topics: Acyclovir; Animals; Female; Genitalia, Female; Guinea Pigs; Herpes Genitalis; Male; Nervous System Diseases; Perfusion; Simplexvirus; Time Factors; Tissue Distribution

Topics: Acyclovir; Female; Herpes Zoster; Humans; Middle Aged; Nervous System Diseases

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