Explore the vast range of titles available.

Oxidative stress, inflammation, and apoptosis have been reported to influence cognitive function in patients with Alzheimer’s disease (AD), particularly those infected with herpes simplex virus type 1 (HSV-1) or cytomegalovirus (CMV). This study aimed to evaluate the effects of viral infection on oxidative stress markers associated with these pathways in AD patients. A total of 100 adults with mild-to-moderate AD were randomly assigned to a double-blind, placebo-controlled clinical trial and categorized into three groups: AD (uninfected), AD with HSV-1, and AD with CMV. The primary outcomes included changes in serum inflammatory markers (IL-1β and TNF-α), blood antioxidant and oxidative stress markers—glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA), reactive oxygen species (ROS), and total antioxidant capacity (TAC), as well as the expression levels of apoptosis-related proteins (BAX and BCL-2). Results showed that, compared to the control group, the AD group exhibited significant alterations in inflammatory and oxidative stress markers. CMV infection led to increased antioxidant enzyme activity and decreased serum inflammatory markers relative to the uninfected AD group. However, there were significant differences in ratio BAX/BCL-2 protein expression between the CMV and HSV-1 groups when compared to the AD group. In conclusion, AD patients infected with HSV-1 or CMV demonstrated distinct alterations in inflammatory, oxidative stress, antioxidant profiles, and apoptosis markers, which may have beneficial implications for circulatory biomarkers and potentially cognitive outcomes in AD.

IntroductionAfter infection, herpes simplex virus-1 (HSV1) becomes latent in the trigeminal ganglion and can enter the brain via retrograde axonal transport. Recurrent reactivation of HSV1 may lead to neurodegeneration and Alzheimer’s disease (AD) pathology. HSV1 (oral herpes) and HSV2 (genital herpes) can trigger amyloid beta-protein (Aβ) aggregation and HSV1 DNA is common in amyloid plaques. Anti-HSV drugs reduce Aβ and phosphorylated tau accumulation in cell-culture models. Cognitive impairment is greater in patients with HSV seropositive, and antiviral drugs show robust efficacy against peripheral HSV infection. Recent studies of electronic health records databases demonstrate that HSV infections increase dementia risk, and that antiviral medication treatment reduces this risk. The generic antiviral drug valacyclovir was superior to placebo in improving memory in a schizophrenia pilot trial but has not been tested in AD.Methods and analysisIn patients with mild AD who test positive for HSV1 or HSV2 serum antibodies, valacyclovir, repurposed as an anti-AD drug, will be compared with placebo (lactose pills) in 130 patients (65 valacyclovir and 65 placebo) in a randomised, double-blind, 78-week phase II proof-of-concept trial. Patients on valacyclovir, dose-titrated from 2 g to a targeted oral dose of 4 g daily, compared with placebo, are hypothesised to show smaller cognitive and functional decline, and, using 18F-Florbetapir positron emission tomography (PET) and 18F-MK-6240 PET imaging, to show less amyloid and tau accumulation, respectively. In the lumbar puncture subsample, cerebrospinal fluid acyclovir will be assayed to assess central nervous system valacyclovir penetration.Ethics and disseminationThe trial is being overseen by the New York State Psychiatric Institute Institutional Review Board (protocol 7537), the National Institute on Ageing, and the Data Safety Monitoring Board. Written informed consent is obtained for all subjects. Results will be disseminated via publication, clinicaltrials.gov, media and conferences.Trial registration numberClinicalTrials.gov identifier (NCT03282916) Pre-results.

Background Encephalitis is an inflammation of the cerebral parenchyma manifested by acute symptoms such as fever, headaches, and other neurological disorders. Its etiology is mostly viral, with herpes simplex virus being a frequent etiological agent in children. The development of neurological sequelae is a serious outcome associated with this infection. Objective To assess the general prevalence and types of neurological sequelae in children after a case of acute viral encephalitis caused by HSV. Methods This systematic review and meta-analysis was developed following the PRISMA guidelines. The literature search was carried out in the MEDLINE, Embase, SciELO, LILACS, Cochrane, CINAHL, PsycINFO, and Web of Science databases. Studies were included of children with confirmed HSV infection and that presented a description of neurological sequelae associated with that infection. For the meta-analysis of general prevalence and of the types of neurological sequelae a random effects model was used. Results Of the 2827 articles chosen in the initial search, nine studies were included in the systematic review and meta-analysis. The general prevalence of neurological sequelae was 50.7% (95% CI 39.2–62.2). The most frequent sequelae were related to mental disability, with a 42.1% prevalence (95% CI 30–55.2); on the other hand, the least frequent sequelae were those related with visual impairment, with a 5.9% prevalence (95% CI 2.2–14.6). The included studies presented regular quality and substantial heterogeneity. Conclusion Even with antiviral therapy, half of patients will develop some type of disability.

Current guidelines recommend brain magnetic resonance imaging (MRI) for clinical management of patients with severe herpes simplex encephalitis (HSE). However, the prognostic value of brain imaging has not been demonstrated in this setting. To investigate the association between early brain MRI data and functional outcomes of patients with HSE at 90 days after intensive care unit (ICU) admission. This multicenter cohort study was conducted in 34 ICUs in France from 2007 to 2019 and recruited all patients who received a clinical diagnosis of encephalitis and exhibited cerebrospinal fluid positivity for herpes simplex virus DNA in the polymerase chain reaction analysis. Data analysis was performed from January to April 2020. All patients underwent a standard brain MRI during the first 30 days after ICU admission. MRI acquisitions were analyzed by radiologists blinded to patients' outcomes, using a predefined score. Multivariable logistic regression and supervised hierarchical classifiers methods were used to identify factors associated with poor outcome at 90 days, defined by a score of 3 to 6 (indicating moderate-to-severe disability or death) on the Modified Rankin Scale. Overall, 138 patients (median [interquartile range {IQR}] age, 62.6 [54.0-72.0] years; 75 men [54.3%]) with an admission median (IQR) Glasgow Coma Scale score of 9 (6-12) were studied. The median (IQR) delay between ICU admission and MRI was 1 (1-7) days. At 90 days, 95 patients (68.8%) had a poor outcome, including 16 deaths (11.6%). The presence of fluid-attenuated inversion recovery MRI signal abnormalities in more than 3 brain lobes (odds ratio [OR], 25.71; 95% CI, 1.21-554.42), age older than 60 years (OR, 7.62; 95% CI, 2.02-28.91), and the presence of diffusion-weighted MRI signal abnormalities in the left thalamus (OR, 6.90; 95% CI, 1.12-43.00) were independently associated with poor outcome. Machine learning models identified bilateral diffusion abnormalities as an additional factor associated with poor outcome (34 of 39 patients [87.2%] with bilateral abnormalities had poor outcomes) and confirmed the functional burden of left thalamic lesions, particularly in older patients (all 11 patients aged >60 years had left thalamic lesions). These findings suggest that in adult patients with HSE requiring ICU admission, extensive MRI changes in the brain are independently associated with poor functional outcome at 90 days. Thalamic diffusion signal changes were frequently observed and were associated with poor prognosis, mainly in older patients.

Background. Herpes simplex virus type 2 (HSV-2) infection is common among human immunodeficiency virus (HIV)-infected persons, and HSV reactivation increases plasma and genital HIV-1 levels. We studied HIV-1 levels during HSV suppression in coinfected persons in a placebo-controlled crossover trial. Methods. Twenty antiretroviral therapy (ART)—naive HIV-1/HSV-2—seropositive men who have sex with men in Lima, Peru, with CD4 cell counts >200 cells/μL were randomized to receive either valacyclovir at 500 mg twice daily or placebo for 8 weeks, after which they underwent a 2-week washout period and then received the alternative regimen for 8 weeks. Specimens included daily anogenital swabs (for HSV DNA polymerase chain reaction [PCR]), thrice weekly rectal mucosal secretions (for HIV-1 RNA and HSV DNA PCR) obtained by anoscopy, and weekly plasma (for HIV-1 RNA PCR). Outcomes were rectal and plasma HIV-1 RNA levels by treatment arm. Results. HIV-1 was detected in 73% of 844 rectal and 99% of 288 plasma specimens. HSV was detected in 29% and 4% of mucocutaneous specimens obtained during placebo and valacyclovir administration, respectively (P< .001). Valacyclovir resulted in a 0.16 (95% confidence interval [CI], 0.07–0.25;P=.0008; 33% decrease) log10copies/mL lower mean within-subject rectal HIV-1 level and a 0.33 (95% CI, 0.23–0.42;P<.0001; 53% decrease) log10 copies/mL lower plasma HIV-1 level, compared with values for placebo. Conclusions. Valacyclovir significantly reduces rectal and plasma HIV-1 levels in HIV-1/HSV-2-coinfected men. HSV suppression may provide clinical benefits to persons not receiving highly active ART as well as public health benefits. Trial registration. ClinicalTrials.gov identifier: NCT00378976.

Objective: To investigate the efficacy and safety of abatacept in combination with etanercept in patients with active rheumatoid arthritis during a 1-year, randomised, placebo-controlled, double-blind phase, followed by an open-label, long-term extension (LTE). Methods: Patients continued etanercept (25 mg twice weekly) and were randomised to receive abatacept 2 mg/kg (n = 85) or placebo (n = 36). As the effective dose of abatacept was established as 10 mg/kg in a separate trial, all patients received abatacept 10 mg/kg and etanercept during the LTE. Results: A total of 121 patients were randomised; 80 completed double-blind treatment and entered the LTE. During double-blind treatment, the difference in the percentage of patients achieving the primary end point (modified American College of Rheumatology (ACR) 20 response at 6 months) was not significant between groups (48.2% v 30.6%; p = 0.072). At 1 year, no notable changes in modified ACR responses were observed. Subsequent to the dosing change, similar modified ACR responses were seen during the LTE. Significant improvements in quality of life were observed with abatacept and etanercept versus placebo and etanercept in five of the eight short-form 36 subscales at 1 year. More abatacept and etanercept-treated patients experienced serious adverse events (SAEs) at 1 year than patients receiving placebo and etanercept (16.5% v 2.8%), with 3.5% v 0% experiencing serious infections. Conclusion: The combination of abatacept (at a dose of 2 mg/kg during the double-blind phase and 10 mg/kg during the LTE) and etanercept was associated with an increase in SAEs, including serious infections, with limited clinical effect. On the basis of the limited efficacy findings and safety concerns, abatacept in combination with etanercept should not be used for rheumatoid arthritis treatment.

Previous trials of corticosteroid or antiviral treatments for Bell's palsy have been underpowered or have had insufficient follow-up. The aim of this study was to compare the short-term and long-term effects of prednisolone and valaciclovir in the recovery of the affected facial nerve in a large number of patients. In this randomised, double-blind, placebo-controlled, multicentre trial, patients aged 18 to 75 years who sought care directly or were referred from emergency departments or general practitioners within 72 h of onset of acute, unilateral, peripheral facial palsy, between May, 2001, and September, 2006, were assessed. Patients were randomly assigned in permuted blocks of eight to receive placebo plus placebo; 60 mg prednisolone per day for 5 days then reduced by 10 mg per day (for a total treatment time of 10 days) plus placebo; 1000 mg valaciclovir three times per day for 7 days plus placebo; or prednisolone (10 days) plus valaciclovir (7 days). Follow-up was for 12 months. The primary outcome event was time to complete recovery of facial function, as assessed with a regional Sunnybrook scale score of 100 points. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00510263. Of 839 patients who were randomly assigned, 829 were included in the modified intention-to-treat analysis: 206 received placebo plus placebo, 210 prednisolone plus placebo, 207 valaciclovir plus placebo, and 206 prednisolone plus valaciclovir. Time to recovery was significantly shorter in the 416 patients who received prednisolone compared with the 413 patients who did not (hazard ratio 1·40, 95% CI 1·18 to 1·64; p<0·0001). There was no difference in time to recovery between the 413 patients treated with valaciclovir and the 416 patients who did not receive valaciclovir (1·01, 0·85 to 1·19; p=0·90). The number of patients with adverse events was similar in all treatment arms. Prednisolone shortened the time to complete recovery in patients with Bell's palsy, whereas valaciclovir did not affect facial recovery. Uppsala University; GlaxoSmithKline (Sweden); Pfizer AB (Sweden); Acta Otolaryngologica Foundation; Rosa and Emanuel Nachmanssons Foundation; Stig and Ragna Gorthon Foundation; Torsten Birger Segerfalk Foundation; Margit Arstrups Foundation; County Council of Skåne; Helsinki University Central Hospital Research Funds.

Background Post herpes simplex virus (HSV) autoimmune encephalitis has been reported mainly in association with NMDA receptor antibodies, however, never with Caspr2 antibodies. Case presentation We report an 82-year old female patient with encephalitis who presented with aphasia, left temporo-mesial hyperintense lesion on MRI, epileptiform discharges on spot electroencephalography, cerebrospinal fluid (CSF) lymphocytic pleocytosis and who showed positive HSV polymerase chain reaction in CSF as well as antibodies against contactin-associated protein-like 2 (Caspr2). Conclusion This is the first report of a patient with encephalitis who tested positive for HSV as well as for Caspr2 antibodies.

We report a baby with neonatal herpes simplex virus (HSV) encephalitis concurrent with Rrhesus (Rh) incompatibility. He was delivered by a Ggravida 2 mother with a history of miscarriage in her previous pregnancy at a gestation age of 4 months. She had Bblood group 0 and Rrhesus negative. The baby was noticed to have jaundice on day one1 of life accompanied by generalised petechiae on the face and upper chest. A full blood picture revealed severe anaemia and severe thrombocytopaenia and HSV 1/2 IgM was positive. MRI of the brain showed multiple extensive haemorrhagic lesions on the frontal-temporal regions.

A randomized cross-over trial of herpes simplex virus type 2 (HSV-2)-suppressive therapy (valacyclovir, 500 mg twice daily, or placebo for 8 weeks, a 2-week washout period, then the alternative therapy for 8 weeks) was conducted among 20 Peruvian women coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) who were not on antiretroviral therapy. Plasma samples (obtained weekly) and endocervical swab specimens (obtained thrice weekly) were collected for HIV-1 RNA polymerase chain reaction. Plasma HIV-1 level was significantly lower during the valacyclovir arm, compared with the placebo arm (−0.26 log10 copies/mL, a 45% decrease [P<.001]), as was cervical HIV-1 level (−0.35 log10 copies/swab, a 55% decrease [P<.001]). Suppressive HSV-2 therapy has the potential to reduce HIV-1 infectiousness and slow HIV-1 disease progression. Trial registration. ClinicalTrials.gov identifier: NCT00465205.