Not Always Toxoplasmosis: Active Retinochoroiditis Presumably Secondary to Herpes in Eyes with Hyperpigmented Retinochoroidal Previous Scars.

PURPOSE: To demonstrate that the presence of active retinochoroiditis in eyes with previous hyperpigmented old retinochoroidal lesions is not exclusive of ocular toxoplasmosis. METHODS: A case series was constructed by reviewing medical records. RESULTS: Four Brazilian patients presenting active posterior uveitis in eyes with previous hyperpigmented old retinochoroidal lesions were identified. Ocular toxoplasmosis was ruled out in all cases. One case had viral etiology confirmed through vitreous PCR (HSV-2 was positive), and the other 3 cases had a presumed diagnosis of herpetic posterior uveitis. CONCLUSION: Focus active retinitis adjacent to an old cicatricial lesion should not be considered pathognomonic of toxoplasmosis and viral etiology must be considered.

Neurexin 3 Regulates Synaptic Connections Between Central Amygdala Neurons and Excitable Cells of the Lateral Parabrachial Nucleus in Rats with Varicella Zoster Induced Orofacial Pain.

Introduction: Herpes Zoster in humans is the result of varicella zoster virus (VZV) infection. Injecting rats with varicella zoster virus produces pain similar to herpes zoster "shingles" pain in humans. . In a previous study, orofacial pain was induced by injecting the whisker pad of male rats with VZV and the pain response increased after attenuating neurexin 3 (Nrxn3) expression in the central amygdala. Neurons descend from the central amygdala to the lateral parabrachial nucleus and orofacial pain signals ascend to the lateral parabrachial nucleus. GABAergic neurons within the central amygdala regulate pain by inhibiting activity within the lateral parabrachial nucleus. Attenuating Nrxn3 expression in the central amygdala increased GABA release in the lateral parabrachial nucleus suggesting Nrxn3 controls pain by regulating GABA release. Nrxn3 can also control synaptic connections between neurons, and we hypothesized that Nrxn3 knockdown in the central amygdala would reduce the number of GABAergic synaptic connections in the lateral parabrachial nucleus and increase VZV associated pain. Methods: To test this idea, the number of synaptic connections between GABAergic cells of the central amygdala and excitatory or dynorphin positive neurons within the lateral parabrachial nucleus were quantitated after infusion of a virus expressing synaptophysin. Synaptophysin is a synaptic vesicle protein that labels neuronal synaptic connections. These connections were measured in rats with and without whisker pad injection of VZV and knockdown of Nrxn3 within the central amygdala. Orofacial pain was measured using a place escape avoidance paradigm. Results: GABAergic synaptic connections were reduced in the lateral parabrachial nucleus after Nrxn3 knockdown. Rats with a reduction in the number of connections had an increase in VZV associated orofacial pain. Immunostaining with the pain marker prodynorphin indicated that the reduction in GABAergic connections was primarily associated with prodynorphin positive neurons. Discussion: The results suggest Nrxn3 reduces VZV associated orofacial pain, in part, by enhancing synaptic connections between GABA cells of the central amygdala and pain neurons within the lateral parabrachial nucleus.

Application of ultrasound-guided thoracic paravertebral block or intercostal nerve block for acute herpes zoster and prevention of post-herpetic neuralgia: A case-control retrospective trial.

OBJECTIVES: Ultrasound (US)-guided intercostal nerve block (ICNB) is an easier approach with a very low incidence of complications for different surgeries; nevertheless, only a few studies estimate the effect of ICNB for acute HZ. To explore the US-guided ICNB for management of herpes zoster (HZ)-related acute pain and possible prophylaxis for post-herpetic neuralgia (PHN) taking the conventional thoracic paraverteral block (TPVB) as control. METHODS: A total of 128 patients with HZ were retrospectively stratified into antiviral treatment (AVT) plus US-guided TPVB (TPVB group), AVT plus US-guided ICNB (ICNB group) or AVT alone (control group) based on the treatment they received. HZ-related illness burden (HZ-BOI) over 30 days after inclusion as the primary endpoint was determined by a severity-by-duration composite pain assessment. Rescue analgesic requirement, health-related quality of life, PHN incidence, and adverse events were also recorded. RESULTS: Significantly lower HZ-BOI scores within post-procedural 30 days using the area under the curve were reported with TPVB and ICNB compared with the control group: mean difference of 57.5 (p < 0.001) and 40.3 (p = 0.003). No difference was reported between TPVB and ICNB (p = 1.01). Significant greater improvements in PHN incidence, EQ-5D-3L scores, and rescue analgesic requirements were observed during follow-up favoring two trial groups, while comparable between two trial groups. No serious adverse events were observed. CONCLUSIONS: US-guided ICNBs were as effective as TPVBs for acute HZ. The ICNB technique was an easier and time-efficient approach as opposed to conventional TPVB, which might be encouraged as a more accessible preemptive mean for preventing PHN.

Efficacy of Mind-Regulating and Depression-Reliving Acupuncture in combination with Radiofrequency Thermocoagulation of Dorsal Root Ganglion for Post-herpetic Neuralgia.

PURPOSE: This study is aimed at evaluating the efficacy of Mind-Regulating and Depression-Relieving Acupuncture in combination with radiofrequency thermocoagulation of DRG for PHN. METHODS: PHN patients who presented to the Pain Department of Affiliated Hospital of Jiaxing University from November 2021 to June 2023 were included. The participants were assigned into two groups using a random number table: Acupuncture + RFTC (Group H, n = 44) group and RFTC (Group C, n = 44) group. The pain numerical rating score (NRS), visual analogue scale scores (VAS), IL-6 , Gal-3, oral dose of tramadol and gabapentin capsules levels were recorded before and after 1, 2, 4, 8 and 12 w of the treatment. RESULTS: After treatment, NRS scores in both groups were significantly lower than pretreatment scores at each time point. Compared with before treatment, the VAS scores at all time points after treatment was increased in both groups. Compared with before treatment, the doses of oral gabapentin capsules and tramadol were reduced in both groups after treatment. Compared with group C, the doses of oral gabapentin capsules and tramadol after the end of the treatment course were significantly reduced in group H. Compared with before treatment, the blood levels of Gal-3 and IL-6 were reduced at all points after treatment in both groups. Compared with group C, the blood Gal-3 and IL-6 levels were significantly reduced in group H. CONCLUSION: Compared with RFTC alone, acupuncture combined with RFTC of DRG has a better therapeutic effect for PHN.

The Topical Novel Formulations of Interferon α-2в Effectively Inhibit HSV-1 Keratitis in the Rabbit Eye Model and HSV-2 Genital Herpes in Mice.

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans.

Parabolic Changes in Pain Scores Among Partial Herpes Zoster Patients: A Retrospective Study.

Background: Herpes zoster (HZ) typically manifests in the acute phase with distinct blisters and severe neuropathic pain. Remarkably, a subset of patients initially presents with only a mild skin rash and moderate pain that gradually intensifies, following a parabolic pattern. Despite being frequently observed in clinical settings, the underlying causes of this trajectory and its potential connection with post-herpetic neuralgia (PHN) remain unclear. Methods: To investigate this phenomenon in-depth, we conducted a meticulous retrospective study involving 529 eligible HZ patients. All these patients sought medical care at the Third Central Hospital of Tianjin, China, between January 2020 and December 2023. Results: The research identified that 14.6% of the sample (77 patients) experienced pain scores aligning with a parabolic curve. This trend was significantly more prevalent in patients aged 60 and above, accounting for 90.9% of this group, and demonstrated a positive correlation with age. Moreover, 87.0% of these patients had pre-existing medical conditions, highlighting the potential role of comorbidities in influencing the pain trajectory. A concerning 45.5% of patients sought medical attention more than seven days after the onset of symptoms, a delay that could exacerbate neurological damage. Notably, among those following a parabolic pain pattern, 66.2% eventually developed PHN, a considerably higher rate compared to the broader patient population. Conclusion: We emphasize that healthcare practitioners meticulously assess patients who initially report lower pain scores for high-risk factors potentially leading to parabolic pain increases, including being over 60 years old, having comorbid conditions, and delaying medical consultation beyond seven days from symptom onset. Early implementation of supplementary pain management therapies may mitigate the risk of PHN development and enhance the quality of life for patients. This study furnishes clinicians with a deeper understanding of the variations in HZ-related pain trajectories, promising to improve treatment approaches and prognoses for HZ patients while paving the way for enriched clinical practice in the future.

Bilateral Multiple Herpetic Epithelial Keratitis: A Case Report and Review of the Literature.

Herpetic epithelial keratitis is a viral infection of the cornea caused by the herpes simplex virus (HSV). It typically presents as a unilateral disease. Bilateral involvement is a rare manifestation of herpetic epithelial keratitis, accounting for only a small percentage of cases. By sharing this case, we aim to contribute to the understanding of bilateral herpetic epithelial keratitis and stimulate further research in this area to optimize patient care and outcomes A 13-year-old child, a known case of atopy, presented to the ophthalmology clinic with a complaint of pain, photophobia, and redness in the right eye (OD) for three days. The patient was diagnosed as a case of bilateral herpetic epithelial keratitis; he was started on moxifloxacin eye drops four times a day, Artelac (sodium hyaluronate) every two hours, carbomer HS, ganciclovir ointment five times per day. Bilateral herpetic epithelial keratitis is a rare manifestation of HSV infection, and its management poses unique challenges compared to unilateral disease. The diagnosis of bilateral herpetic epithelial keratitis is primarily based on clinical findings, including bilateral dendritic or geographic ulcers on the cornea. Fluorescein staining is a valuable tool for visualizing corneal ulcers. In our case, the presence of bilateral dendritic ulcers in the absence of significant anterior chamber inflammation supported the diagnosis of bilateral herpetic epithelial keratitis Despite the limited literature on bilateral herpetic epithelial keratitis, the principles of management remain consistent with those of unilateral disease. Early recognition, prompt initiation of antiviral therapy, and close follow-up are crucial for successful outcomes.

CRISPR/Cas9-mediated genome editing of the thymidine kinase gene in a clinical HSV-1 isolate identifies F289S as novel acyclovir-resistant mutation.

Herpes simplex virus type 1 (HSV-1) is a neurotropic alphaherpesvirus that establishes a lifelong infection in sensory neurons of infected individuals, accompanied with intermittent reactivation of latent virus causing (a)symptomatic virus shedding. Whereas acyclovir (ACV) is a safe and highly effective antiviral to treat HSV-1 infections, long-term usage can lead to emergence of ACV resistant (ACVR) HSV-1 and subsequently ACV refractory disease. Here, we isolated an HSV-1 strain from a patient with reactivated herpetic eye disease that did not respond to ACV treatment. The isolate carried a novel non-synonymous F289S mutation in the viral UL23 gene encoding the thymidine kinase (TK) protein. Because ACV needs conversion by viral TK and subsequently cellular kinases to inhibit HSV-1 replication, the UL23 gene is commonly mutated in ACVR HSV-1 strains. The potential role of the F289S mutation causing ACVR was investigated using CRISPR/Cas9-mediated HSV-1 genome editing. Reverting the F289S mutation in the original clinical isolate to the wild-type sequence S289F resulted in an ACV-sensitive (ACVS) phenotype, and introduction of the F289S substitution in an ACVS HSV-1 reference strain led to an ACVR phenotype. In summary, we identified a new HSV-1 TK mutation in the eye of a patient with ACV refractory herpetic eye disease, which was identified as the causative ACVR mutation with the aid of CRISPR/Cas9-mediated genome engineering technology. Direct editing of clinical HSV-1 isolates by CRISPR/Cas9 is a powerful strategy to assess whether single residue substitutions are causative to a clinical ACVR phenotype.

Eczema exacerbation following herpes zoster infection in an immunocompetent patient: A case report.

This case report highlights a severe eczematous rash manifesting broadly across the scalp, face, and neck of a 54-year-old female following a resolved herpes zoster infection. Notably, such cutaneous reactions post-varicella zoster virus infection, which may present weeks to years after the acute phase, have been documented but remain poorly understood in their pathogenesis. This patient exhibited a blistering rash diagnosed as shingles with overlying cellulitis, initially treated with valacyclovir and cefalexin. Upon returning with a diffuse rash post-treatment, further examination and tests led to a differential diagnosis that most closely aligned with eczema exacerbation with superimposed bacterial infection, confirmed by the presence of methicillin-resistant Staphylococcus aureus. Treatment encompassed intravenous vancomycin, ciprofloxacin eye drops, topical hydrocortisone, betamethasone lotion, and gabapentin, leading to substantial improvement. This case underscores the complexity of diagnosing and managing cutaneous reactions post-varicella zoster virus infection and suggests a multimodal treatment approach may yield favorable outcomes.

[Recurrent herpetic erosion of the cornea: diagnosis, treatment and prevention of recurrences]. / gerpeticheskaya retsidiviruyushchaya eroziya rogovitsy: diagnostika, lechenie i preduprezhdenie retsidivov.

A group of patients was found to have a special form of recurrent corneal erosion caused by types I and II herpes virus. This form represents an independent form of ophthalmic herpes - herpetic recurrent erosion (HRE) of the cornea. The herpetic etiology of recurrent corneal erosion was confirmed by the immunofluorescence study of scraping from the conjunctiva, which revealed a high concentration of the herpes simplex virus antigen. Treatment of patients (171 patients, 182 eyes) with HRE included 2 consecutive stages: stage I - relief of acute symptoms of the disease with the help of conservative treatment (instillations of interferon inducers, autologous serum, corneal protectors, tear substitutes, use of therapeutic soft contact lenses); in some cases, phototherapeutic keratectomy was used in the absence of the effect of conservative therapy, as well as in the localization of the focus in the optical zone. Stage II involved anti-relapse therapy based on the use of a Russian-produced herpes vaccine in the intercurrent period. After vaccination, observation for 2 years or more showed that 81.3% of patients achieved clinical recovery (complete cessation of HRE recurrences), 15.8% had a decrease in the frequency and severity of relapses, while 2.9% of patients did not respond to the treatment.

Public health impact of herpes zoster vaccination on older adults in Singapore: a modeling study.

In Singapore, population aging and rising life expectancy are increasing herpes zoster (HZ) burden, which may be reduced by vaccination. The present study modeled the public health impact of HZ vaccination in Singapore using ZOster ecoNomic Analysis (ZONA) model adapted with Singapore-specific key model inputs, where available. Base case analysis was conducted in adults ≥ 50 years of age (YOA), exploring three vaccination strategies (no vaccination, recombinant zoster vaccine [RZV], zoster vaccine live [ZVL]) under mass vaccination setting (30% coverage). Scenario and sensitivity analyses were performed. Out of 1.51 million adults in 2021 (base case population), 406,513 (27.0%) cases of HZ, 68,264 (4.5%) cases of post-herpetic neuralgia (PHN), and 54,949 (3.6%) cases of other complications were projected without vaccination. RZV was estimated to avoid 73,129 cases of HZ, 11,094 cases of PHN, and 9,205 cases of other complications over the subjects' remaining lifetime; ZVL would avoid 17,565 cases of HZ, 2,781 cases of PHN, and 1,834 cases of other complications. The number needed to vaccinate to prevent one case of HZ/PHN was lower for RZV (7/41) than ZVL (26/163). Among all five age-stratified cohorts (50-59/60-64/65-69/70-79/≥80 YOA), RZV (versus no vaccination/ZVL) avoided the largest number of cases in the youngest cohort, 50-59 YOA. Results were robust under scenario and sensitivity analyses. Mass vaccination with RZV is expected to greatly reduce the public health burden of HZ among Singapore individuals ≥ 50 YOA. Findings support value assessment and decision-making regarding public health vaccination strategies for HZ prevention in Singapore.

Risk of shingles (herpes zoster) increases with age, especially from 50 years. Shingles is a major public health concern in Singapore, given its rapidly aging population. Vaccination can prevent shingles and reduce its public health burden. Two shingles vaccines are available in Singapore: recombinant zoster vaccine (RZV) since 2021, zoster vaccine live (ZVL) since 2008. To understand the value of preventing shingles via vaccination, this study assessed the public health impact of shingles vaccination. Three vaccination strategies (no vaccination, vaccination with RZV, vaccination with ZVL) were compared in 1.51 million Singapore adults aged 50 years and above. Without vaccination, public health burden of shingles would be high; an estimated 406,513 (27.0%) would have shingles, 68,264 (4.5%) would have shingles-related long-term nerve pain, 54,949 (3.6%) would have other shingles-related complications, and 17,762 (1.2%) would be hospitalized due to shingles. Shingles vaccination could reduce this public health burden: RZV avoided 73,129 cases of shingles, 11,094 cases of shingles-related long-term nerve pain, 9,205 cases of other shingles-related complications, and 2,827 hospitalizations due to shingles, which was 4­6 times that avoided with ZVL (shingles: 17,565; shingles-related long-term nerve pain: 2,781; other shingles-related complications: 1,834; hospitalizations due to shingles: 484). Shingles vaccination for adults aged 50 years and above, especially early vaccination from 50­59 years, could reduce its public health burden more than vaccination at later ages and contribute toward healthy aging, preventive care, and the Healthier SG initiative. Results support local public health value assessments and decision-making for shingles prevention.

Short-Term Supraorbital Nerve Stimulation and Pain Relief for Acute and Subacute Ophthalmic Herpetic Neuralgia: A Randomized Controlled Crossover Trial.

BACKGROUND: Herpes zoster ophthalmicus (HZO) is a kind of refractory disease, and treating it is important for preventing postherpetic neuralgia (PHN). But the evidence surrounding the current treatment options for these conditions is controversial, so exploring reasonable clinical treatment strategies for HZO is necessary. Neuromodulation is an excellent modality for the treatment of various neuropathic pain conditions. This trial was designed to evaluate the effectiveness of short-term supraorbital nerve stimulation (SNS) and the supraorbital nerve block (SNB) for HZO. OBJECTIVES: To determine whether short-term SNS relieves acute and subacute ophthalmic herpetic neuralgia. STUDY DESIGN: This prospective randomized controlled crossover trial compared short-term SNS to SNB. SETTING: The operating room of a pain clinic. METHODS: Patients with acute or subacute ophthalmic herpetic neuralgia were recruited. The patients were randomly assigned to receive either SNS or SNB. The primary outcome being measured was each patient's Visual Analog Scale (VAS) score at 4 weeks. The secondary outcomes under measurement were the proportion of patients who achieved ≥ 50% pain relief, sleep quality, medicine consumption, and adverse events. Crossover after 4 weeks was permitted, and patients were followed up to 12 weeks. RESULTS: Overall, 50 patients were included (n = 25/group). At 4 weeks, the patients who received SNS achieved greater pain relief, as indicated by their significantly different VAS scores from those of the SNB group (mean difference: -1.4 [95% CI, -2.29 to -0.51], P < 0.05). Both groups showed a significant decrease in pain level from the baseline (all P < 0.05). Overall, 72% and 44% of the SNS and SNB patients experienced ≥ 50% pain relief, respectively (OR: 0.31 [95% CI, 0.09 to 0.99], P < 0.05), and 68% and 32% of SNS and SNB patients, respectively, had VAS scores < 3 (OR: 0.22 [95% CI, 0.07 to 0.73], P < 0.05). Compared to the SNB group, the SNS group had better sleep quality, lower ophthalmic neuralgia, a lower proportion of further treatment, and lower analgesic intake. Overall, 18 patients received SNS alone, and 16 patients crossed over from SNB to SNS. The VAS scores, sleep quality, ophthalmic neuralgia, and trend of medicine intake were not significantly different between the groups (all P > 0.05). No serious complications occurred. LIMITATIONS: This study was nonblind. CONCLUSIONS: Short-term SNS is effective for controlling acute or subacute ophthalmic herpetic neuralgia. Combining SNS with SNB yields no additional benefits.

A Retrospective Comparison of Low-Temperature Plasma Ablation and Radiofrequency Thermocoagulation of the Thoracic Nerve Root for Refractory Postherpetic Neuralgia.

BACKGROUND: Radiofrequency thermocoagulation (RFT) of the thoracic nerve root is commonly employed in treating medication-refractory thoracic post-herpetic neuralgia (PHN). However, RFT procedures' suboptimal pain relief and high occurrence of postoperative skin numbness present persistent challenges. Previous single-cohort research indicated that the low-temperature plasma coblation technique may potentially improve pain relief and reduce the incidence of skin numbness. Nevertheless, conclusive evidence favoring coblation over RFT is lacking. OBJECTIVES: To compare the clinical outcomes associated with coblation to those associated with RFT in the treatment of refractory PHN. STUDY DESIGN: Retrospective matched-cohort study. SETTING: Affiliated Hospital of Capital Medical University. METHODS: Sixty-eight PHN patients underwent coblation procedures between 2019 and 2020, and 312 patients underwent RFT between 2015 and 2020 in our department. A matched-cohort analysis was conducted based on the criteria of age, gender, weight, pain intensity, pain duration, side of pain, and affected thoracic dermatome. Pain relief was assessed using the numeric rating scale (NRS), the Medication Quantification Scale (MQS) Version III and the Neuropathic Pain Symptom Inventory (NPSI), which were employed to indicate pain intensity, medication burden, and comprehensive pain remission at 6, 12, and 24 months. Numbness degree scale scores and complications were recorded to assess safety. RESULTS: We successfully matched a cohort of 59 patients who underwent coblation and an equivalent number of patients who underwent RFT as a PHN treatment. At the follow-up time points, both groups' NRS, MQS, and NPSI scores exhibited significant decreases from the pre-operation scores (P < 0.05). The coblation group's NRS scores were significantly lower than the RFT group's at the sixth and the twenty-fourth months (P < 0.05). At 24 months, the MQS values in the coblation group were significantly lower than those in the RFT group (P < 0.05). Furthermore, the coblation group's total intensity scores on the NPSI were significantly lower than the RFT group's at the 12- and 24-month follow-ups (P < 0.05). At 6 months, the coblation group's temporary intensity scores on the NPSI were significantly lower than the RFT group's (P < 0.05). Notably, the occurrence of moderate or severe numbness in the coblation group was significantly lower than in the RFT group at 6 and 12 months (P < 0.05). No serious adverse effects were reported during the follow-up. LIMITATIONS: This analysis was a single-center retrospective study with a small sample size. CONCLUSION: In this matched cohort analysis, coblation achieved longer-term pain relief with a more minimal incidence rate of skin numbness than did RFT. Further randomized controlled trials should be conducted to solidify coblation's clinical superiority to RFT as a PHN treatment.

Radiological Features of Herpetic Encephalitis in Children.

BACKGROUND: Nonspecific clinical manifestations and unclear radiological features may delay treatment initiation in pediatric patients with Herpes simplex encephalitis (HSE). The aim of this study is to analyze the clinical and radiological features of the disease. METHODS: Clinical, laboratory, and magnetic resonance imaging (MRI) data were obtained retrospectively from a group of 37 hospitalized pediatric patients older than two months and with a polymerase chain reaction-confirmed HSE diagnosis. Clinical severity (i.e., mechanical ventilatory support) and outcome at discharge (i.e., pediatric modified Rankin Scale [ped-mRS]) were also assessed. RESULTS: Median age was 14 months (interquartile range: 10-36). All patients survived, 15 (41%) had complete recovery (i.e., ped-mRS = 0), and 10 (27%) had significant residual disability at discharge (i.e., ped-mRS ≥3). Brain MRI was obtained in 31 patients. T2-hyperintense lesions were usually bilateral (28, 90%) and multifocal (30, 97%). Hemorrhage and mass effect were observed in 13 (42%) and 15 (48%) patients, respectively. Parenchymal lesions involved the temporal lobes (94%), insula (90%), parietal lobes (84%), and frontal lobes (61%). Occipital lesions were rare. In multivariable binary logistic regression models the presence of altered consciousness was associated with mechanical ventilation (odds ratio [OR] = 8.2, Nagelkerke R2 = 0.22), whereas the involvement of the occipital lobes (OR = 7.8) and the administration of vasopressors (OR = 12.1) were independent predictors of poor outcome (Nagelkerke R2 = 0.41). CONCLUSIONS: Brain MRI is useful for diagnosis and outcome assessment in pediatric HSE. Radiological patterns with common frontotemporal involvement overlap adults, but multifocal and parietal lobe abnormalities are observed as well.

Herpetic Keratouveitis: Missed Diagnosis Leading to Corneal Perforation.

Herpetic uveitis is an easy diagnosis to miss, which can lead to devastating consequences. The aim of this report is to create awareness of how this disease can present, appropriate clues to the diagnosis, and how it should be managed. We report a case of a 70-year-old female who presented with redness and painless blurry vision in her right eye and was treated with topical corticosteroid drops for presumed idiopathic anterior uveitis. Despite initial symptomatic improvement, she reattended with a significant deterioration in vision and was found to have a large corneal infiltrate and associated perforation. The perforation was sealed with corneal gluing, and she was treated for presumed herpetic anterior uveitis with oral acyclovir. Corneal polymerase chain reaction (PCR) specimen was positive for herpes simplex virus DNA. The perforation started to leak again despite repeat corneal gluing, so an emergency therapeutic penetrating keratoplasty was performed. She has remained on prophylactic oral acyclovir for the last 24 months, with no recurrence and the graft remains clear.

Atypical Peripheral Retinal Necrosis Without Ocular Inflammation and Retinal Whitening in a Patient With Acute Myelogenous Leukemia: A Case Report.

Retinal necrosis is a severe condition that threatens visual function. It is caused by viruses that are known to cause acute retinal necrosis (ARN) and progressive outer retinal necrosis (PORN), which are called necrotizing herpetic retinopathies (NHR). ARN causes severe intraocular inflammation, including anterior chamber intravitreal cells, keratic precipitate, vitreous opacity, and retinal vasculitis, whereas intraocular inflammation in PORN is considered mild or virtually absent. In addition, PORN is a disease that manifests in immunosuppressive patients, such as those with acquired immunodeficiency syndrome. Here, we present a case of unilateral retinal necrosis after chemotherapy, allogeneic peripheral blood stem cell transplantation, and cord blood transplantation for acute myelogenous leukemia (AML) in a 31-year-old male patient. AML treatment resulted in metabolic remission, and oral steroids and tacrolimus were continued. After two days, the patient visited an ophthalmologist because he noticed a sudden onset of floaters and visual field disturbance in the left eye. The peripheral retina was already necrotic in all layers, causing total retinal detachment. Intraocular inflammation, retinal opacity, or hemorrhagic spots in the fundus were not observed. His previous CD4 count was 43 cells/µL. A polymerase chain reaction test of the anterior chamber fluid revealed varicella-zoster virus (VZV), and vitrectomy was performed four days after disease onset. The excised vitreous demonstrated minimal opacity. The peripheral necrotic retina was excised, photocoagulation was performed on the residual retinal limbus, and silicone oil was injected to maintain retinal attachment. The retinal restoration was maintained under silicone oil tamponade, and corrected visual acuity improved to 20/32 without strong inflammation after vitrectomy. However, two months postoperatively, he contracted coronavirus disease 2019 (COVID-19), his general condition rapidly deteriorated, and he died. This case of retinal necrosis without inflammatory results in an immunocompromised patient and VZV detection in an intraocular sample led us to suspect PORN. However, the patchy or spread retinal whitening characteristic of PORN was completely absent, whereas the well-defined, peripheral, full-layer retinal necrosis characteristic of ARN was present. Thus, this is a rare case of VZV-induced NHR with partial features of PORN and ARN that progressed very silently.

Chronic inflammation as a proposed risk factor for ocular surface squamous neoplasia.

PURPOSE: Chronic inflammation is a predisposing factor for metaplastic changes and ultimately dysplasia. We describe cases of OSSN occurring in the setting of chronic ocular surface inflammation. METHODS: Sixteen eyes from 14 individuals were included from one ocular oncology clinic between 2010 and 2023. Patients presented with ocular surface squamous neoplasia (OSSN) in the setting of chronic inflammation. The diagnosis of OSSN was made using anterior segment high-resolution optical coherence tomography (HR-OCT) and confirmed by histopathological analysis in all cases. RESULTS: Median age on presentation was 61 [IQR 47.5-69.2] years. Eleven (86%) individuals were male and five (36%) identified as White Hispanic. Ten eyes were referred with ocular surface diagnoses including pannus (n = 4), scarring (n = 3), pterygium (n = 2), and herpetic keratitis (n = 1). Only six eyes were referred as possible neoplasia. All individuals had a history of ocular surface inflammation. The most common inflammatory conditions were ocular rosacea (seven individuals) and atopic keratoconjunctivitis (AKC) (five individuals). Two individuals were found to have bilateral OSSN, one in the setting of ocular rosacea and the other in the setting of AKC. All 16 eyes from 14 individuals were suspected to have OSSN based on HR-OCT findings which guided the location of the incisional biopsies that subsequently confirmed histopathological diagnosis in all cases. CONCLUSION: OSSN may arise in the setting of chronic inflammation on the ocular surface. Identification of the tumor can be challenging in these cases, and HR-OCT can be a key diagnostic tool in detecting OSSN.

Bovine herpesvirus meningoencephalitis in the State of Tocantins, Brazil.

Three outbreaks of herpesvirus meningoencephalitis in cattle have been reported in three municipalities in the northern region of the State of Tocantins, Brazil. In one outbreak, 41 predominantly young bovines were affected, with 2-3 deaths in some cases. The animals showed neurological signs of incoordination, blindness, and recumbency, with death occurring within approximately 4-5 d. At necropsy, hyperemia and leptomeningeal hemorrhages were observed in the brain. Histology revealed more intense lesions in the rostral portions of the brain, mainly affecting the frontoparietal cerebral cortex, with nonsuppurative encephalitis and meningitis, glial nodules, neuronophagia, and eosinophilic intranuclear inclusion bodies in the astrocytes and neurons. This study shows the presence of bovine herpesvirus in Tocantins, probably the highly neurotropic type 5 strain, and emphasizes its importance in the differential diagnosis of bovine neuropathies.

Três surtos de meningoencefalite por herpesvírus em bovinos são relatados em três municípios da região norte do Estado do Tocantins, Brasil. Num surto, 41 animais predominantemente jovens foram afetados, com 2-3 mortes nos outros casos. Os animais apresentaram sinais neurológicos de incoordenação, cegueira e decúbito, com a morte ocorrendo em aproximadamente 4 a 5 dias. Na necropsia foram observadas hiperemia e hemorragias leptomeníngeas no encéfalo. A histologia revelou lesões mais intensas nas porções rostrais do encéfalo, principalmente no córtex cerebral frontoparietal, com encefalite e meningite não supurativas, nódulos gliais, neuronofagia e corpúsculos de inclusão intranucleares eosinofílicos nos astrócitos e neurônios. Este estudo demonstra a presença do herpesvírus bovino no Tocantins, provavelmente a cepa tipo 5 altamente neurotrópica, e enfatiza sua importância no diagnóstico diferencial das neuropatias bovinas.

HSV-1 reactivation results in post-herpetic neuralgia by upregulating Prmt6 and inhibiting cGAS-STING.

Chronic varicella zoster virus (VZV) infection induced neuroinflammatory condition is the critical pathology of post-herpetic neuralgia (PHN). The immune escape mechanism of VZV remains elusive. As to mice have no VZV infection receptor, herpes simplex virus type 1 (HSV-1) infection is a well established PHN mice model. Transcriptional expression analysis identified that the protein arginine methyltransferases 6 (Prmt6) was upregulated upon HSV-1 infection, which was further confirmed by immunofluorescence staining in spinal dorsal horn. Prmt6 deficiency decreased HSV-1-induced neuroinflammation and PHN by enhancing antiviral innate immunity and decreasing HSV-1 load in vivo and in vitro. Overexpression of Prmt6 in microglia dampened antiviral innate immunity and increased HSV-1 load. Mechanistically, Prmt6 methylated and inactivated STING, resulting in reduced phosphorylation of TANK binding kinase-1 (TBK1) and interferon regulatory factor 3 (IRF3), diminished production of type I interferon (IFN-I) and antiviral innate immunity. Furthermore, intrathecal or intraperitoneal administration of the Prmt6 inhibitor EPZ020411 decreased HSV-1-induced neuroinflammation and PHN by enhancing antiviral innate immunity and decreasing HSV-1 load. Our findings revealed that HSV-1 escapes antiviral innate immunity and results in PHN by upregulating Prmt6 expression and inhibiting the cGAS-STING pathway, providing novel insights and a potential therapeutic target for PHN.