valacyclovir and Encephalitis--Herpes-Simplex

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

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

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

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

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

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

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

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

Topics: Animals; Antiviral Agents; Base Sequence; Blood-Brain Barrier; Brain; Chlorocebus aethiops; Encephalitis, Herpes Simplex; Genes, Reporter; Genes, Viral; Herpesvirus 1, Human; Luminescence; Mice; Mice, Inbred BALB C; Multiplex Polymerase Chain Reaction; Valacyclovir; Vero Cells; Viral Load; Virus Replication

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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