acyclovir and Central-Nervous-System-Diseases

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

Topics: Acyclovir; Amantadine; Antiviral Agents; Central Nervous System Diseases; Ganciclovir; Humans; Rimantadine; Vidarabine

With increasing use of acyclovir and ganciclovir, primarily due to the increased number of AIDS and transplant patients, further cases of neurologic toxicity will undoubtedly be encountered. Discontinuation or dosage reduction of acyclovir and ganciclovir is necessary to manage neurologic toxicity that is directly attributed to either agent. Renal dysfunction is a known risk factor for acyclovir neurotoxicity, and case reports indicate that renal dysfunction may also be a risk factor for ganciclovir neurotoxicity. Since ganciclovir is structurally related to acyclovir, clinicians should monitor for signs and symptoms of neurotoxicity as they would with acyclovir until the risk factors are more clearly defined. Dosage reduction for both agents and increased monitoring should occur when renal dysfunction is present, to minimize the risk of neurotoxicity and other serious adverse effects. Tables 1 and 2 summarize the recommended dosages of acyclovir and ganciclovir, respectively, in the presence of renal dysfunction. However, as a few case reports describe, neurotoxicity from these agents has also occurred in patients with normal renal function. Therefore, clinicians should always remain vigilant in monitoring for signs of neurotoxicity when acyclovir or ganciclovir is administered, and have a high index of suspicion for these agents if neurotoxicity is encountered during therapy.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Central Nervous System Diseases; Cytomegalovirus Infections; Ganciclovir; Herpes Simplex; Herpes Zoster; Humans; Renal Insufficiency; Risk Factors

Herpes simplex virus infections of the central nervous system remain a significant cause of morbidity and mortality, in spite of safe and efficacious antiviral therapy. Advances in the treatment of neonatal herpes and herpes simplex encephalitis with acyclovir have improved outcome. The application of polymerase chain reaction has allowed for the prompt and specific diagnosis of herpes simplex virus infections of the brain. This review summarizes our current knowledge on the pathogenesis, diagnosis, and treatment of herpes simplex virus infections of the brain. Opportunities for the future will be defined.

Topics: Acyclovir; Adult; Central Nervous System Diseases; Herpes Simplex; Humans; Infant; Infant, Newborn; Polymerase Chain Reaction

Acyclovir produces neurologic symptoms that resemble extension of viral infection into the central nervous system. We discuss our observations in the cases of two patients with acyclovir neurotoxicity and review the findings of all previous reports in the English language literature. Systemic disease, most commonly renal dysfunction, preceded all 30 reported cases of acyclovir neurotoxicity. The most common symptoms were mental status disorder and involuntary movements. Measurement of serum acyclovir levels substantiated the diagnosis in only a subset of patients. Although all patients recovered, hemodialysis hastened the rate of recovery.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Central Nervous System Diseases; Cytomegalovirus Infections; Female; Herpes Simplex; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Most of the human herpesviruses have a unique relationship with the central nervous system. In this review we summarize recent developments in the establishment of viral latency, and discuss the nervous system illnesses instigated by direct viral cytopathic effect, by immune activation, and by neoplastic events. Special consideration is given to herpesvirus infections in the context of acquired immunodeficiency syndrome, and in association with neonatal infections. New diagnostic techniques and treatments are also summarized.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Central Nervous System Diseases; Central Nervous System Neoplasms; Herpesviridae; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Polymerase Chain Reaction; Tumor Virus Infections

Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease.. We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy.. A total of 74 neonates were enrolled--45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P=0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P=0.09).. Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.).

Topics: Acyclovir; Antiviral Agents; Central Nervous System Diseases; Child Development; Double-Blind Method; Female; Herpes Simplex; Humans; Infant, Newborn; Kaplan-Meier Estimate; Male; Pregnancy Complications, Infectious; Secondary Prevention

Neonatal herpes simplex virus (HSV) infections are recognized to be severe because of their association with significant morbidity and mortality. Through ongoing studies performed by the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group, the presentation, natural history, outcome and value of antiviral chemotherapy have been considered. Infants developing neonatal HSV infections can be classified according to the extent of disease, disseminated or localized. Localized infection can be subdivided into either central nervous system (CNS) disease, occurring in 35% of infected infants, or skin, eye and mouth (SEM) disease, in 41% of infants. Disseminated disease accounts for 24% of neonatal HSV infection. Therapeutic outcome depends upon disease classification. Administration of either 15 or 30 mg/kg/day of vidarabine resulted in significantly decreased mortality for infants with life-threatening disseminated and CNS disease as compared to placebo recipients. Approximately one-third of children developed normally following disseminated disease or CNS infection. When disease was localized to the SEM, no death occurred, and 88% of treated infants developed normally. While these data indicate that therapy is effective for management of infants with neonatal HSV infection, improvements are necessary. Hopefully, a study in progress will demonstrate improved outcome with acyclovir treatment.

Topics: Acyclovir; Central Nervous System Diseases; Clinical Trials as Topic; Female; Herpes Genitalis; Herpes Simplex; Humans; Infant, Newborn; Keratitis, Dendritic; Pregnancy; Pregnancy Complications, Infectious; Recurrence; Risk; Skin Diseases, Infectious; Stomatitis, Herpetic; Vidarabine

Renal dysfunction is a significant risk factor for acyclovir-induced neurotoxicity and altered mentation and myoclonic movements are the most common clinical symptoms observed. In majority of reported cases, neurological sequelae associated with acyclovir-induced neurotoxicity often mimic viral infections of the central nervous system and makes diagnosis of the former challenging. Although plasma concentrations of the drug may not always correlate with neurotoxic symptoms, obtaining serum levels of acyclovir may be helpful in confirming drug-induced neurotoxicity. Hemodialysis has been shown to significantly improve altered mentation in patients with suspected or confirmed acyclovir-induced neurotoxicity. Here, we report a definite case of acyclovir-induced neurotoxicity in a patient with end-stage renal disease. Clinical improvements in neurologic symptoms were observed following discontinuation of the drug and hemodialysis.

Topics: Acyclovir; Antiviral Agents; Central Nervous System Diseases; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neurotoxicity Syndromes; Renal Dialysis

Aciclovir is effective in herpesvirus infections of the CNS. Aciclovir-induced neuropsychiatric symptoms (AINS) have been reported and are associated with high CSF concentrations of aciclovir metabolite 9-carboxymethoxymethylguanine (CMMG). Risk factors except for renal failure have not been explored, and disruption of the blood-brain barrier (BBB) in acute CNS infection may be of interest.. To investigate the impact of risk factors on aciclovir and CMMG concentrations, and to relate the results to AINS.. We investigated 21 consecutively included, consenting patients treated with aciclovir or valaciclovir for herpesvirus CNS infection. Regression models were constructed to study the impact of risk factors including BBB disruption, as measured with CSF:serum albumin ratio, on CSF aciclovir and CMMG concentrations. Medical records were assessed retrospectively to identify patients with AINS.. Increased CSF:serum albumin ratio, as well as decreased renal function and high aciclovir doses, was associated with increased aciclovir and CMMG concentrations in the CSF. We identified five patients with new neuropsychiatric symptoms; four of those were considered to have AINS and had increased CSF CMMG concentrations. Only one patient without suspicion of AINS had an increased CSF CMMG concentration.. In patients with herpesvirus CNS infections, BBB disruption is associated with increasing aciclovir and CMMG CSF concentrations. We also found an unexpectedly high number of patients with AINS. Evaluation of CSF:serum albumin ratios, renal function and CSF concentrations of aciclovir and CMMG may all contribute to the optimization of aciclovir dosing and avoidance of AINS.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Blood-Brain Barrier; Central Nervous System Diseases; Female; Guanine; Herpesviridae Infections; Humans; Male; Mental Disorders; Middle Aged; Prospective Studies; Retrospective Studies; Risk Factors

We aimed to compare the changes in renal function indicators as a function of hydration volume in patients treated with acyclovir for suspected herpes simplex virus (HSV) infection.. We obtained data from 216 acyclovir-treated patients hospitalized between 2007 and 2012 for suspected HSV infection. Intravenous hydration volume and renal function indicators (serum creatinine [sCr], blood urea nitrogen [BUN], glutamate oxaloacetate transferase, glutamate pyruvate transferase, and uric acid levels; estimated glomerular filtration rate [eGFR]; and urine pH) were compared among the patients. The indicators were assessed before acyclovir infusion and after 3 days of acyclovir infusion.. Before acyclovir infusion, all the indicators were within normal ranges in all groups (hydration volume lower than 2 L/day, higher than 2 L/day, and without hydration). After acyclovir infusion for 3 days, the groups without hydration and with a volume lower than 2 L/day showed increased sCr (2.22 ± 0.51 and 1.70 ± 0.35 mg/dl, respectively), BUN levels (28.33 ± 0.57 and 22.14 ± 7.95 mg/dl, respectively), and glutamate oxaloacetate transferase (48.00 ± 2.65 IU/L, without hydration) and eGFRs lower than the normal range (53.03 ± 3.05 and 59.66 ± 10.25 ml/min, respectively; p < .001 for all parameters). The renal function indicators were within normal limits in the group with a hydration volume higher than 2 L/day.. Renal function indicators in acyclovir-treated patients varied according to hydration volume. Health care providers should consider whether the hydration volume in each patient receiving intravenous acyclovir is sufficient for preventing nephropathy.

Topics: Acyclovir; Adult; Antiviral Agents; Central Nervous System Diseases; Female; Fluid Therapy; Herpes Simplex; Humans; Infusions, Intravenous; Kidney Function Tests; Male; Middle Aged; Retrospective Studies

Topics: Acyclovir; Adult; Antiviral Agents; Brain Diseases; Central Nervous System Diseases; Cerebral Arterial Diseases; Chickenpox; Fatal Outcome; Fever; Glomerulonephritis; Herpesvirus 3, Human; Humans; Kidney Transplantation; Magnetic Resonance Imaging; Male

A boy at 12 days of age developed neonatal herpes simplex virus (HSV) type 2 infection with central nervous system (CNS) disease. After a 21-day course of high-dose intravenous acyclovir, the patient recovered with negative results for HSV DNA in serum and cerebrospinal fluid. Two weeks after a 6-month course of oral valacyclovir suppressive therapy with negative virological assessment, the disease recurred. Another 21-day course of intravenous acyclovir and subsequent 1-year course of oral suppressive therapy were completed. He showed mild developmental delay in language-social skills at 18 months of age. Although recurrences of neonatal HSV infection with CNS disease after suppressive therapy are uncommon, both clinical and virological assessments at the end of the suppressive therapy may be required. Administration of extended long-term suppressive ACV therapy should be considered to reduce the rate of recurrence.

Topics: Acyclovir; Antiviral Agents; Central Nervous System Diseases; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; Male; Pregnancy Complications, Infectious; Recurrence

Topics: Acyclovir; Antiviral Agents; Central Nervous System Diseases; Child Development; Female; Herpes Simplex; Humans; Male; Pregnancy Complications, Infectious

Topics: Acyclovir; Antiviral Agents; Central Nervous System Diseases; Child Development; Female; Herpes Simplex; Humans; Male; Pregnancy Complications, Infectious

To highlight diagnostic and management features of auditory neuropathy/auditory dyssynchrony (AN/DS) due to central demyelinating disorder.. A child with AN/DS due to central nervous system pathologic findings.. Audiometry, auditory brainstem response (ABR) test, otoacoustic emission test, magnetic resonance imaging (MRI) with gadolinium contrast, intravenous corticosteroid treatment, antiviral treatment, stereotactic biopsy, and cyclophosphamide immunomodulation.. Pure-tone audiometry, speech discrimination testing, ABR, and MRI.. A 12-year-old girl presented with acute sensorineural hearing loss, abnormal ABR, and normal otoacoustic emissions consistent with AN/DS. The hearing loss demonstrated fluctuation and corticosteroid responsiveness. Magnetic resonance imaging and stereotactic biopsy revealed brainstem demyelination consistent with multiple sclerosis. Definitive treatment consisted of cyclophosphamide immunomodulation.. Although recent focus on pathophysiology of AN/DS has shifted from auditory nerve abnormalities to dyssynchrony within the cochlea, cases associated with fluctuating sensorineural hearing loss and responsiveness to corticosteroid therapy should raise the suspicion of central nervous system pathologic findings. Therefore, it is crucial to obtain brain MRI with contrast enhancement in all patients with AN/DS. This is critical in patients undergoing cochlear implantation because MRI may be contraindicated postoperatively.

Topics: Acyclovir; Adrenal Cortex Hormones; Antiviral Agents; Audiology; Audiometry, Pure-Tone; Central Nervous System Diseases; Child; Cochlear Nerve; Cyclophosphamide; Evoked Potentials, Auditory, Brain Stem; Female; Gadolinium; Hearing Loss, Unilateral; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Multiple Sclerosis; Myelin Sheath; Speech Discrimination Tests; Vestibulocochlear Nerve Diseases

Herpes simplex virus (HSV) infections of the central nervous system (CNS) can occur within weeks after birth (neonatal HSV disease) or in childhood or adulthood [herpes simplex encephalitis (HSE)]. Most cases of neonatal HSV disease are caused by HSV type 2, whereas virtually all cases of HSE are caused by HSV type 1. Diagnostic advances made during the past decade include the application of polymerase chain reaction (PCR) technology to cerebrospinal fluid from patients with suspected HSV CNS disease to evaluate for the presence of HSV DNA. Although not foolproof, PCR is a powerful diagnostic tool that has supplanted brain biopsy as the modality of choice for diagnosing HSV CNS disease, in no small part because of the invasiveness of brain biopsy. PCR also can provide information regarding the therapeutic response to antiviral therapy. Efforts made during the past decade to improve the outcome of HSV CNS disease have focused on increased doses of intravenous acyclovir administered for longer durations of time. Although advances have been achieved, morbidity and mortality rates from neonatal HSV disease and HSE remain unacceptably high.

Topics: Acyclovir; Antiviral Agents; Central Nervous System Diseases; Encephalitis, Viral; Female; Herpes Simplex; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infectious Disease Transmission, Vertical; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Infectious; Risk Factors; Simplexvirus

Chickenpox is a common infection of childhood in countries that have not included the corresponding vaccination in their immunization schedules. Chickenpox is usually benign in immunocompetent children, and treatment is not needed. The objectives of this study were to investigate the frequency and characteristics of chickenpox complications that require hospital treatment in immunocompetent children and the clinical progression in children of mothers with perinatal chickenpox. In addition, the hospital costs associated with chickenpox in the studied children were calculated.. This was a retrospective study using the clinical records of children with chickenpox hospitalized at the Children's Hospital of Panama, from January 1991 through December 2000. We analyzed the types of complications, the clinical progression, and the hospital costs of the chickenpox patients.. Of 5 203 children seen in outpatient consultations, 568 of them (11%) were hospitalized. We included 513 children in our study: 381 (74%) with chickenpox acquired in the community, 92 (18%) the children of mothers with chickenpox, and 40 (8%) with nosocomial chickenpox. The most frequent complications were cutaneous and subcutaneous infections (45%), respiratory infections (25%), and neurological changes (7%). The respiratory and cutaneous complications occurred sooner and among younger patients than did the neurological changes. Overall, 13 of the children (2.5%) died. The case fatality rate was 8% for chickenpox with respiratory and neurological complications and 0% for chickenpox with cutaneous complications. Of the 92 children with a mother with chickenpox, 60 of them (65%) did not develop the disease, and none of the 92 died. In contrast, 2 of the 32 neonates (6%) with perinatal chickenpox died. The mean length of hospitalization was 8.9 days (standard deviation, +/- 17.4 days). Parenteral pharmacotherapy was used with the great majority of the children, particularly antibiotics (54%), acyclovir (17%), and intravenous immunoglobulin (14%). The mean per-patient cost of hospitalization was US$ 1 209.. Our results show that chickenpox is associated with a sizable number of expensive complications and a not-insignificant case fatality rate in immunocompetent children. Routine vaccination against chickenpox could reduce the impact of this disease on the health of children in Panama

Topics: Acyclovir; Antiviral Agents; Central Nervous System Diseases; Chickenpox; Child; Child, Preschool; Cost-Benefit Analysis; Female; Hospitalization; Humans; Immunization; Immunocompetence; Immunoglobulins, Intravenous; Infant; Infant Mortality; Infant, Newborn; Male; Maternal Exposure; Respiratory Tract Infections; Retrospective Studies; Skin Diseases

The aim of this study was to correlate human herpesvirus (HHV)-6 viral load with clinical symptoms in allogeneic stem cell transplant (SCT) patients. Seventy-four patients were monitored during the first 3 months after SCT using a qualitative polymerase chain reaction (PCR) for HHV-6 DNA. HHV-6 was detected in 181 out of 494 samples (36%) from 58 (78%) patients. These 181 samples were analysed using a quantitative competitive PCR. DNA could be quantified from 146 out of 181 samples (80.6%). The HHV-6 viral load was highest at 4 weeks compared with 8 weeks (P < 0.001) and 12 weeks (P = 0.01) after SCT. Three patients had HHV-6 encephalitis and one patient had hepatitis. The HHV-6 DNA levels were higher in patients with HHV-6 than in those without HHV-6 (P = 0.01). Patients who received grafts from unrelated or HLA-mismatched family donors had significantly higher HHV-6 DNA levels than patients who received grafts from matched sibling donors (P < 0.001). In a multiple regression model, unrelated donor grafts (P < 0.001) and use of intravenous immunoglobulin prophylaxis (P = 0.04) influenced HHV-6 DNA levels. HHV-6 viral load was significantly correlated with delayed platelet engraftment in both univariate (P < 0.01) and multivariate analysis, and to the number of platelet transfusions.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Blood Platelets; Bone Marrow Transplantation; Central Nervous System Diseases; Child; Child, Preschool; Cytomegalovirus; DNA, Viral; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hepatitis; Herpesviridae Infections; Herpesvirus 6, Human; Histocompatibility Testing; Humans; Immunoglobulins, Intravenous; Leukocytes; Male; Middle Aged; Multivariate Analysis; Platelet Transfusion; Polymerase Chain Reaction; Postoperative Period; Prospective Studies; Transplantation, Homologous; Viral Load

In persons with AIDS (PWAs), cytomegalovirus (CMV) infection can cause a broad spectrum of clinical manifestations. The most common clinical manifestations associated with CMV infection in PWAs and the most current approaches to treatment and prevention of CMV disease are reviewed. Manifestations discussed include those involving ocular disease, and diseases of the gastrointestinal and central nervous systems. Prophylactic treatment for CMV disease includes the use of oral ganciclovir and valaciclovir. Concluding comments address the development of antiviral resistance by CMV. Tables include listings of potential strategies for use of oral ganciclovir prophylaxis in PWAs, and mechanisms by which CMV strains become resistant to ganciclovir, foscarnet, and cidofovir.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Central Nervous System Diseases; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Digestive System Diseases; Foscarnet; Ganciclovir; Humans; Valacyclovir; Valine

A case of renal failure in a patient with severe central nervous system symptoms during oral acyclovir medication is reported. A 68-year-old man maintained on hemodialysis was given oral acyclovir 4,000 mg daily in divided doses because of herpes zoster affecting the left C3/5 dermatomes. He had vomiting and confusion 36 hours after administration. He had no focal neurological signs. The symptoms resolved 4 days after cessation of acyclovir administration and blood purification every day. Because of its high therapeutic index the use of acyclovir is associated with few side effects. In patients with renal failure the half-life of acyclovir is prolonged, this report indicates the importance of adhering to the dosage reductions in patients with renal failure.

Topics: Acyclovir; Administration, Oral; Aged; Central Nervous System Diseases; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Renal Dialysis

A 31-year-old woman with systemic lupus erythematosus (SLE) developed meningoencephalitis, followed by transverse myelitis. The clinical picture was otherwise not consistent with a lupus flare. Extensive diagnostic evaluation was unrevealing. Acute visual loss ensued, associated with an unusual pattern of retinitis. Endoretinal biopsy established the diagnosis of herpesvirus infection. Reinstitution of antiviral therapy, and optic nerve sheath decompression, led to resolution of neurologic deficits and partial return of vision. Our report is the first that describes a patient with SLE with herpes meningoencephalitis, transverse myelitis, and rapidly progressive outer retinal necrosis, diagnosed antemortem by endoretinal biopsy, and successfully treated with acyclovir and optic nerve fenestration.

Topics: Acyclovir; Adult; Biopsy; Central Nervous System Diseases; Combined Modality Therapy; Female; Herpesviridae Infections; Humans; Lupus Erythematosus, Systemic; Meningoencephalitis; Myelitis, Transverse; Opportunistic Infections; Retinitis

Topics: Acyclovir; Agranulocytosis; Antibodies, Viral; Central Nervous System Diseases; Chickenpox; Child; Herpesvirus 3, Human; Humans; Leukopenia; Liver Diseases; Male; Neutropenia

Three renal transplant patients with culture-positive central nervous system infections resulting from varicella-zoster virus died of the virus infection. No finding predicting a poor outcome in these patients could be identified. Varicella-zoster infection in transplant recipients is a potentially fatal disease, and upon diagnosis should it be treated by (1) reduction in immunosuppression, and (2) initiation of either vidarabine or acyclovir as specific antiviral therapy.

Topics: Acyclovir; Adult; Central Nervous System Diseases; Herpes Zoster; Humans; Kidney Transplantation; Male; Middle Aged; Vidarabine

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

Hamsters are very susceptible to infections with herpes simplex virus. Inoculation of the skin of the lower back region leads to an ascending involvement of the central nervous system with fatal outcome. This model was used for testing the activity of antiviral substances in herpes infections of the nervous system. Acyclovir given in optimal dosages prevented infection of the central nervous system completely even when therapy was started 48 hours after inoculation. Therapy with acyclovir proved to be successful in animals showing paresis after infection even when the drug was given in lower than optimal dosages.

Topics: Acyclovir; Animals; Antiviral Agents; Brain; Central Nervous System Diseases; Cricetinae; Guanine; Herpes Simplex; Mesocricetus; Paralysis; Simplexvirus; Spinal Cord; Time Factors