Reversible splenial lesion syndrome (RESLES), mild encephalitis/encephalopathy with a reversible splenial lesion (MERS), and cytotoxic lesions of the corpus callosum (CLOCCs) are overlapping clinicoradiological constructs associated with infection, seizures, metabolic disturbance, and drug exposure. We report an 11-year-old right-handed boy with recurrent paroxysmal speech arrest over approximately 24 hours. During the episodes, consciousness and comprehension were preserved; he could vocalize and communicate by typing but could not produce meaningful speech. Transient left upper-limb or generalized weakness and upper respiratory symptoms accompanied the spells. Respiratory adenovirus testing was positive, and a Mycoplasma pneumoniae (M. pneumoniae) antibody titer was reported as 1:160, although respiratory and cerebrospinal fluid M. pneumoniae polymerase chain reaction testing was negative. Cerebrospinal fluid contained 1 white cell/microL, with normal protein, glucose, and chloride and mildly elevated interleukin-6 (IL-6). Baseline electroencephalography showed abundant right frontopolar, frontal, anterior temporal, and Fz interictal discharges without a captured electroclinical seizure. Magnetic resonance imaging demonstrated a splenial lesion with symmetric posterior periventricular and centrum semiovale abnormalities, compatible with a type II MERS/RESLES pattern or CLOCC-spectrum process. He received two 40 g doses of intravenous immunoglobulin (IVIG) and later intravenous methylprednisolone followed by oral prednisone, together with empirical acyclovir, azithromycin, mannitol, and supportive care. No further speech arrest or weakness was documented on or after illness day 5, and methylprednisolone was initiated on illness day 6. Follow-up electroencephalography on illness day 48 showed qualitatively fewer discharges confined to sleep, but no habitual event. Serial imaging showed lesion regression with residual fluid-attenuated inversion recovery (FLAIR) signal on illness day 74. At approximately 4.5 months, he remained asymptomatic during prednisone tapering. Because formal language and motor-speech testing was not performed during an episode, aphasia could not be definitively distinguished from anarthria, dysarthria, apraxia of speech, or focal speech arrest. This case highlights the diagnostic overlap among resolving callosal-white matter lesions, transient speech-output disturbance, and interictal epileptiform abnormalities, while cautioning against attributing recovery to a single treatment or equating residual magnetic resonance signal with active inflammation.

Epstein-Barr virus-associated smooth muscle tumours (EBV-SMTs) are rare neoplasms typically affecting immunosuppressed individuals such as organ transplant recipients. This case follows a woman in her 30s who presented with multi-organ masses 5 years after a kidney transplant. While initial suspicion focused on common post-transplant infections or malignancy, a liver biopsy revealed a smooth muscle neoplasm positive for EBV by EBV-encoded RNA in-situ hybridisation, consistent with EBV-SMT. Managing EBV-SMT is challenging as no standardised treatment regimens exist. When reducing immunosuppression-the conventional first-line approach-failed, a multidisciplinary team opted for a non-standard regimen including Valganciclovir and Pazopanib, which is not a recognised therapy for this condition. The patient achieved a partial metabolic response and maintained stable disease at a 2 year follow-up. This case emphasises the importance of considering this differential when encountering spindle cell neoplasms in an immunosuppressed setting while highlighting the necessity of establishing standardised treatment guidelines for this rare disease.

Viral infections are common in pregnancy and contribute significantly to maternal and fetal/neonatal morbidity and mortality. Certain viruses cause congenital infection with potentially devastating fetal/neonatal consequences, ranging from structural anomalies (birth defects), fetal growth restriction, and stillbirth to congenital viral syndromes with long-term end-organ damage and neurodevelopmental disorders. While a comprehensive review of all viral infections in pregnancy is beyond the scope of this article, this review focuses on the management of herpes simplex virus and cytomegalovirus.

Human cytomegalovirus (HCMV) infection is widespread within the global human population and is a major cause of human morbidity and mortality. As yet, there is no widely available anti-HCMV vaccine strategy. Therefore, treatment of HCMV disease relies on anti-HCMV drugs, principally the nucleoside analogue pro-drug ganciclovir (GCV). While it is over 40 years since the discovery of GCV as an anti-HCMV compound, the use of GCV in humans is still developing, for example in the treatment of congenital HCMV infection. Here, we provide an overview of often overlooked virological laboratory studies underpinning GCV development. We highlight long-standing, but rarely examined, data on adverse effects that is the basis for caution in using GCV during pregnancy or in children. This includes discussion of recent, contrasting data, suggesting that GCV can be further developed to treat congenital HCMV infection. To better understand how adverse effects may come about, we also review the viral and cellular factors required for GCV function in HCMV-infected and uninfected cells. This leads to a discussion of how adverse effects of GCV may or may not be avoided and future directions involving the use of GCV. Overall, these topics highlight how much molecular information remains to be understood about one of the oldest and most widely used anti-HCMV drugs in humans.

Respiratory syncytial virus (RSV) is a prevalent viral respiratory infection that has been increasingly affecting children under 5 years old globally. Although RSV can infect individuals of all ages, certain groups are at higher risk, particularly infants and young children. This growing concern underscores the urgent need for effective therapeutic options. In this context, drug repurposing emerges as a promising strategy, allowing existing medications to be utilized for new therapeutic applications beyond their original indications. In this research, we utilized library of FDA-approved antiviral drugs that show potential for repurposing. We performed molecular docking against RSV nucleoprotein. The two resulting drugs, ganciclovir and acyclovir, reveal notable binding energy and critical interactions. Further ADMET profile and prediction of activity spectra for substances (PASS) analysis show potential to be antiviral drugs against nucleoprotein. Furthermore, molecular dynamics simulations for 500 ns were conducted, along with calculations of principal component analysis (PCA) and Gibbs free energy for the most promising ligand-receptor complexes identified in docking ADMET and PASS analysis (ganciclovir and acyclovir). The simulations provided insights into their thermodynamic and dynamic properties, further investigating the docking results. The findings from this study offer valuable leads for the development of therapeutic agents against RSV. However, to substantiate the preventive and therapeutic potential of these compounds, further validations, including in vitro, animal studies, and rigorous clinical trials, are necessary.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an uncommon but recognized complication of herpes zoster (varicella-zoster virus, VZV) infection, and diagnostic uncertainty may arise when hyponatremia develops after antiviral therapy is initiated. We report an 89-year-old patient with hypertension, chronic kidney disease stage 3, hyperlipidemia, and prior left nephrectomy for renal cell carcinoma who presented with right neck and upper arm pain, weakness, and a unilateral dermatomal vesicular eruption consistent with herpes zoster. Oral acyclovir was started at 800 mg five times daily. During hospitalization, serum sodium declined from 136 mEq/L to a nadir of 123 mEq/L despite discontinuation of hydrochlorothiazide. The patient remained clinically euvolemic, with urine sodium of 134 mEq/L and urine osmolality of 570 mOsm/kg, supporting SIADH. Thyroid-stimulating hormone and morning cortisol were normal. Fluid restriction < 1.2 L/day was ineffective. As the patient became symptomatic, and hypertonic saline (with removal of fluid restriction) produced no improvement, a single dose of tolvaptan produced rapid correction of serum sodium and improvement in mentation. The patient was subsequently maintained on sodium chloride tablet supplementation, fluid restriction, and a high-protein diet, with serum sodium improving to 135-136 mEq/L. This case describes severe hypotonic euvolemic hyponatremia meeting biochemical criteria for SIADH in the setting of localized herpes zoster, after consideration of concurrent hydrochlorothiazide exposure and temporally associated oral acyclovir.

Varicella-zoster virus (VZV) is a neurotropic alpha herpesvirus capable of producing a wide spectrum of CNS disease, ranging from aseptic meningitis and vasculopathy to encephalitis and myelitis. Less widely appreciated is its capacity to extend centrally along the trigeminal pathway into the brainstem, producing intra-axial spinal trigeminal tract involvement that may remain clinically silent or manifest only as a cranial neuropathy, particularly when cerebrospinal fluid (CSF) polymerase chain reaction (PCR) is negative. We describe an immunocompetent 41-year-old man who presented with herpes zoster of the left hemiface in a maxillary-mandibular (V2-V3) distribution, followed by an acute left lower motor neuron facial palsy, initially indistinguishable from Ramsay Hunt syndrome. In the absence of encephalopathy, limb weakness, or cerebellar signs, magnetic resonance imaging of the brain demonstrated linear non-enhancing fluid-attenuated inversion recovery (FLAIR) hyperintensity extending across the posterior pons, medulla, and upper cervical cord, corresponding to the course of the spinal trigeminal tract and nucleus. CSF showed lymphocytic pleocytosis with otherwise unremarkable biochemistry; both herpes simplex virus and VZV PCR were negative. The patient was managed with intravenous acyclovir for 14 days, alongside short-course corticosteroids and supportive care. A transient rise in serum creatinine was managed with hydration and close monitoring while full-dose acyclovir was continued, without acyclovir-related neurotoxicity. Recovery was marked, with the House-Brackmann grade improving from V to III over follow-up and corresponding radiological regression of the brainstem signal change. The picture is best understood as sequential trigeminal-then-facial cranial neuropathy with longitudinally extensive spinal trigeminal tract involvement attributable to centripetal VZV spread, rather than a rhombencephalitic clinical syndrome. Such a combination -- trigeminal-territory zoster with longitudinally extensive spinal trigeminal tract involvement and an isolated facial palsy -- has only rarely been reported. This case illustrates the diagnostic dilemma of PCR-negative VZV CNS disease and underscores the value of clinicoradiological correlation, early antiviral therapy, and close neurological surveillance when a peripheral facial palsy emerges in the setting of cephalic herpes zoster.

Herpetic gingivostomatitis (HGS) is a common manifestation of herpes simplex virus type 1 (HSV-1) infection in children and is usually mild and self-limiting. We report the case of an eight-year-old boy with a known history of developmental delay who presented with prolonged fever and painful oral ulcers. The patient presented eight days after symptom onset. The lesions rapidly spread to involve the lips, tongue, and buccal mucosa, forming thick hemorrhagic crusts. He developed severe anemia that required transfusion and failed to improve with topical acyclovir and antibiotics. Upon presentation to our hospital, intravenous acyclovir was started with supportive therapy. His condition improved markedly, and the lesions resolved. This case describes an unusual, severe, hemorrhagic presentation of HGS in an immunocompetent child. It highlights that systemic antiviral therapy can lead to clinical improvement even when initiated later in the disease course and underscores the need for further studies to define optimal management for severe cases.

Herpes simplex virus (HSV) infections are widespread and cause a significant global health burden. Clinical manifestations range from herpes labialis and genital herpes to life-threatening herpes simplex encephalitis or neonatal herpes. Current treatment relies on nucleoside analogs such as acyclovir, valacyclovir or famciclovir. The emergence of resistance to these drugs is of concern in transplant recipients and immunocompromised patients. Next-generation helicase-primase inhibitors are under clinical development to provide more efficacious treatments and address resistance to current therapies. Adibelivir (IM-250) is a potent HSV helicase-primase inhibitor (HPI) with nanomolar activity against both HSV1 and HSV2. In the present study, we assessed the susceptibility of more than 50 clinical isolates and laboratory strains against adibelivir. Across all strains tested, adibelivir inhibited HSV replication in cell culture with mean EC50 values of 21 nM (HSV1) and 35 nM (HSV2), compared to up to 42-fold higher EC50 values for acyclovir (883 nM for HSV1 and 1456 nM for HSV2). No preexisting variants with a lack of susceptibility were identified. Furthermore, no cross-resistance was observed between nucleoside analogs and HPIs and finally, the antiviral activity depended on serum concentration and infectious dose. Collectively, these data establish the baseline susceptibility profile of HSV clinical isolates to adibelivir prior to its broader clinical introduction. Adibelivir retains activity against nucleoside-resistant HSV strains and exhibits synergistic antiviral effects when combined with acyclovir, penciclovir and foscarnet in vitro. These results support clinical evaluation of adibelivir as a therapeutic option for HSV infections and as a candidate for combination therapy.

Herpes is a viral disease with high worldwide prevalence. The lack of herpes vaccines and the growing viral resistance to acyclovir and its analogues create an urgent need for new treatment strategies. Anionic polysaccharides, especially sulfated derivatives, can inhibit herpes simplex virus (HSV) infection by interfering with viral attachment to heparan sulfate on host cells. Building on our previous work, we designed and prepared a heparan sulfate-mimetic derivative of botryosphaeran, a fungal β-glucan, by sequential oxidation and sulfonation. Firstly, oxidation converted approximately one-half of the C-6 primary hydroxyl groups into carboxyl groups, yielding BOTOX. Subsequent sulfonation yielded the heparan sulfate mimetic (BOTOX/SULF) with a degree of sulfonation of 0.3 and sulfate groups mainly at C-6 of the remaining glucose units. In vitro assays showed that BOTOX/SULF had high anti-HSV-1 activity, while BOTOX was inactive. The antiviral effect of BOTOX/SULF was comparable to that of previously reported botryosphaeran sulfonated derivatives with a higher degree of sulfonation, suggesting that the combined presence of carboxylate and sulfate groups contributes to activity. These results support heparan sulfate mimicry as a promising strategy for designing entry inhibitors against enveloped viruses.