Primary diffuse leptomeningeal melanomatosis (PDLM) is an exceptionally rare and aggressive central nervous system melanocytic tumour, often masquerading as inflammatory or infective leptomeningeal disease. A woman in her early 60s presented with hydrocephalus and diffuse leptomeningeal enhancement, initially treated as neurosarcoidosis. This progressed, despite immunosuppression, and repeated lumbar punctures yielded no cerebrospinal fluid (CSF) ('dry taps'). Intradural biopsy identified a melanocytic neoplasm with a GNA11 mutation. Fewer than 25 cases of isolated PDLM have been reported, and misdiagnosis is common. MRI typically shows T1-hyperintense leptomeningeal lesions but CSF is often non-diagnostic. Repeated failure to obtain CSF is a potential clinical clue to extensive leptomeningeal tumour infiltration. PDLM should be considered in atypical, treatment-refractory leptomeningeal disease. Recognising its characteristic imaging features and obtaining early biopsy are important to avoiding diagnostic delay.

Middle meningeal artery (MMA)-directed interventions have been described for refractory headache syndromes, including migraine and aneurysmal subarachnoid hemorrhage-associated headache. We present a Neuro-Interventional Video demonstrating intra-arterial lidocaine-guided MMA coil embolization for severe refractory side-locked headache after ipsilateral internal carotid artery flow-diverter placement. The patient denied active headache or migraine immediately before flow-diverter treatment, but postprocedural headaches were documented at 1-month follow-up. The patient subsequently developed severe refractory side-locked right temporal headache without focal neurologic deficit or explanatory imaging correlate. Right external carotid angiography demonstrated a patent, moderately tortuous MMA. An SL-10 microcatheter was advanced into the frontal division beyond the orbital roof; hand injection demonstrated catheter tip position beyond orbital anastomotic branches. Intra-arterial lidocaine (27 mg) produced immediate improvement from 8/10 to 0/10 without neurologic or visual symptoms, followed by targeted coil occlusion of the selected frontal MMA territory. The accompanying video demonstrates patient selection, angiographic safety assessment, lidocaine response, coil deployment, and post-embolization confirmation. This single case is hypothesis-generating; the relative contributions of lidocaine and embolization and longer-term durability require further study.

Differentiating gliomas from meningiomas and assessing imaging features related to glioma infiltration remain challenging with conventional magnetic resonance imaging (MRI). Amide Proton Transfer (APT) imaging, a chemical exchange saturation transfer technique, can detect changes in tissue protein content and pH, offering potential functional insights into brain tumors. This retrospective study evaluated APT imaging combined with conventional MRI in 105 patients with pathologically confirmed brain tumors (55 meningiomas, 20 low-grade gliomas [LGGs], and 30 high-grade gliomas [HGGs]). APT-derived mean signal intensity (APTmean) and the ratios of APT abnormal area to T2 hyperintense area (RAPT/T2) and to contrast-enhancing area (RAPT/E) were measured and compared among groups. APTmean was significantly higher in HGGs (median 4.60%) than in LGGs (2.95%) and meningiomas (2.70%, P < 0.001). RAPT/T2 and RAPT/E were also markedly elevated in HGGs. For distinguishing HGGs from meningiomas, APTmean achieved excellent diagnostic performance (area under the curve [AUC] = 0.969), compared with RAPT/E (0.836) and RAPT/T2 (0.800). For differentiating LGGs from meningiomas, RAPT/E (AUC = 0.781) and RAPT/T2 (AUC = 0.734) showed good performance, whereas APTmean did not differ significantly. For glioma grading (HGG vs. LGG), APTmean yielded an AUC of 0.916, superior to contrast enhancement degree (0.823). These findings indicate that APT imaging effectively distinguishes meningiomas from gliomas of different grades and provides valuable imaging-based information for inferring the extent of tumor infiltration. The combination of APTmean and spatial extent ratios provides a practical imaging tool for improving preoperative diagnosis and supporting surgical planning, particularly in challenging atypical cases.

Neonatal bacterial meningitis is a leading cause of infant morbidity and mortality, yet the molecular and cellular basis of the leptomeningeal response to infection remains poorly defined. Here, we study a mouse model of neonatal Escherichia coli meningitis, combining conditional gene knockouts, leptomeningeal single-nucleus RNA sequencing, and endothelial cell culture to explore the role of Toll-like receptor 4 (TLR4) signaling in the host response to infection. Deletion of Tlr4 in non-myeloid cells dramatically reduced the inflammatory response in all leptomeningeal cell types and abrogated the infection-associated increase in vascular permeability. In a brain endothelial cell line (bEnd.3 cells), exposure to E. coli triggered NF-κB activation, selective internalization of Claudin-5, and increased monolayer permeability, responses that were eliminated by Tlr4 knockout. RNA-seq showed that TLR4 controls an NF-κB-driven transcriptional program that orchestrates the endothelial response to E. coli. These findings reveal multiple TLR4-dependent host responses to neonatal Gram-negative bacterial meningitis.

Streptococcus suis serotype 2 (SS2) is a major zoonotic pathogen that causes severe meningitis and high mortality in both humans and swine. Growing evidence shows that metabolites generated along the gut-brain axis regulate neuroinflammation. In this study, we demonstrate that oral administration of sodium butyrate (NaB) (300 or 600 mg/kg/day) for 28 days lowered mortality and lessened neuropathological signs in mice infected with SS2 (SC19 strain). Butyrate prophylaxis was associated with lower bacterial loads in the blood and brain tissue, preserved expression of tight junction proteins (ZO-1, Claudin-5, and Occludin) in the brain, and maintained blood-brain barrier (BBB) integrity and permeability. 16S rRNA sequencing analysis revealed that SC19 infection significantly diminished the diversity and richness of the gut microbiota, notably depleting key short-chain fatty acid (SCFA)-producing bacterial taxa. Butyrate intervention restored microbial homeostasis and enriched SCFA-producing communities. Mechanistically, butyrate was associated with upregulated expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant effectors (heme oxygenase 1 [HO-1] and NQO1), while inhibiting phosphorylation of NF-κB p65 and the secretion of proinflammatory cytokines (interleukin-1β [IL-1β], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]) in human cortical microvessels endothelial cells/D3 (hCMEC/D3) cells. Critically, these protective effects were abrogated upon pharmacological inhibition of Nrf2, indicating the critical role of Nrf2 in butyrate-mediated attenuation of neuroinflammation and oxidative stress. Our findings highlight the prophylactic potential of modulating the gut-brain axis as a novel strategy to mitigate central nervous system (CNS) infections associated with foodborne pathogens.

Meningitis, an acute and life-threatening inflammation of the protective membranes covering the brain and spinal cord caused primarily by bacterial, viral, fungal, or parasitic infections, remains a major global health challenge, causing significant morbidity and mortality, particularly among children and vulnerable populations. The Sri Lankan epidemiological unit reported approximately 1000-1500 meningitis cases annually. This review summarizes current knowledge on meningitis in Sri Lanka, drawing on global evidence and locally published studies to examine epidemiology, clinical presentation, diagnostic approaches, immunity gap, and future priorities. Most studies indicate that bacterial meningitis, particularly caused by Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae, remains the most severe and clinically significant form. Viral etiologies, especially enteroviruses, are also commonly reported. Although the introduction of the H. influenzae Type b (Hib) vaccine has significantly reduced disease burden, important immunity gaps persist due to limited pneumococcus serotype coverage and the absence of routine meningococcal vaccination. Diagnostic challenges, including delays in cerebrospinal fluid collection, limited access to molecular testing, and preanalytical errors, hinder early detection and accurate pathogen identification. Future directions should focus on strengthening molecular diagnostic capacity, strengthening point-of-care rapid antigen assays and decentralized molecular diagnostics, expanding serotype surveillance, improving sample collection practices, and evaluating the feasibility of introducing meningococcal vaccination into the national immunization schedule. Bridging these gaps is essential for aligning Sri Lanka's efforts with global targets outlined in the World Health Organization's (WHO) Defeating Meningitis by 2030 roadmap.

Accurate diagnosis of bacterial meningitis is critical, particularly in young febrile infants. Although commercially available multiplex PCR assays enable rapid pathogen detection, these typically do not include Salmonella spp. or other Enterobacteriaceae, which may result in missed diagnoses and/or inappropriate treatment duration. We report the case of a 2-month-old female infant with Salmonella enteritidis meningitis and concurrent bacteremia. The patient initially presented with fever, lethargy, and a bulging anterior fontanelle. Cerebrospinal fluid (CSF) analysis was highly suggestive of bacterial meningitis. However, both CSF culture and the FilmArray ME Panel were negative, likely due to prior empirical antibiotic therapy at another hospital. The causative organism was isolated on blood cultures. The infant was treated with intravenous ceftriaxone for 24 days and discharged in excellent clinical condition. Twelve days later, she was readmitted with a relapse of meningitis and bacteremia caused by the same pathogen. She received combination therapy with cefotaxime and cotrimoxazole for 37 days, followed by cefotaxime monotherapy for another 26 days. Immunological evaluation, including assessment of immunoglobulin levels, lymphocyte subsets, and interferon-γ receptor and Interleukin-12 receptor expression, was normal. The patient had a favorable outcome with complete clinical and laboratory recovery and a normal neurodevelopmental outcome at follow-up. Salmonella meningitis is a rare but life-threatening condition in infants, which may be overlooked when relying on molecular diagnostic panels that do not include this pathogen. Negative CSF PCR results should be interpreted with caution in the presence of typical cytological and biochemical findings of bacterial meningitis. Prolonged antimicrobial therapy of at least 4-6 weeks is essential to prevent relapse and ensure optimal microbiologic and clinical outcomes.

Linezolid is an alternative to vancomycin for treating Gram-positive central nervous system (CNS) healthcare-associated infections, but its optimal dosing remains debated. The PK-Pop-LCR prospective population pharmacokinetic/pharmacodynamic (PK/PD) study included acute brain injured (ABI) patients with an external ventricular drainage (EVD) receiving linezolid. A population PK model developed using plasma and cerebrospinal fluid (CSF) data, and Monte Carlo simulations calculated the probability of target attainment (PTA) and cumulative fraction of response (CFR) in CSF against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). PD targets for CSF were AUC/MIC > 70 and 100% T> MIC. Toxicity thresholds (plasma Cmin,ss > 7 mg/L and AUCss > 300mg.h/L) was also assessed. CNS infections were confirmed in 14 of 25 patients included. Median AUCCSF/unbound AUCplasma ratio was around 80% for all patients despite higher CSF cytokines levels in CNS-infected patients. EVD flow rate influenced linezolid CSF exposure. For AUCCSF/MIC, 1200 mg/24h allowed to reach PTAs ≥90% only for MICs<1 mg/L, and CFR of 11.2% (MRSA) and 67.0% (MRSE). For T>MIC, 1200mg by continuous infusion (CI) would achieve CFR>95% for MRSE, while 2400mg (CI) would be needed for MRSA (PTA>90% for MIC=4mg/L; CFR = 95%) but with around 40% toxicity risk. We confirmed the extensive CSF distribution of linezolid. Higher doses (2400mg CI) may be considered for probabilistic treatment of CNS infection in ABI patients, despite CSF PK/PD targets further investigated. Early individualized dose adjustment based on MIC and drug monitoring is essential to balance efficacy and safety.

Rift Valley fever virus (RVFV) is a zoonotic arbovirus transmitted by a wide range of mosquito vectors present across the African continent. RVFV has resulted in large-scale epidemics in East, West, southern, and northern Africa with additional epidemics affecting the Arabian Peninsula, Mayotte, and Comoros. In some areas, rather than large-scale isolated outbreaks, RVFV causes a fluctuating low-level endemic burden affecting livestock populations by resulting in pregnancy loss and significant production losses. RVFV risk extends into the human population when it is transmitted either by vector-borne transmission or direct contact with infected animals or animal products such as blood, meat, or milk. Following infection, 2%-3% of humans can develop severe disease manifestations including encephalitis/meningitis, hemorrhagic fever, and retinitis, with visual deficits commonly reported among survivors. While RVF cases in animals and humans have been spatially linked, the proportion and risk associated with spillover events is poorly classified. Given RVFV's dual threat to human and livestock health, it has been designated a priority pathogen by WHO for development of countermeasures. This review aims to summarize current knowledge of RVFV epidemiology, infection, and control as well as highlight key recent advances in the understanding of epidemiology and vaccine development. Multiple next-generation vaccine candidates have advanced to phase two clinical trials which offer hope for approved and commercially available human vaccines in the coming decades. However, despite these promising advancements, key gaps in knowledge remain, particularly regarding the total burden and geographic distributions of endemic and epidemic infections, shifting epidemiologic patterns, optimal vaccine use cases, and the effects of RVFV infection on pregnancy in humans living in hyperendemic regions. Many gaps in understanding persist, and RVFV remains a quintessential One Health pathogen requiring coordinated human, animal, and environmental investigation and collaboration to translate scientific advances into effective national public health strategies.

BACKGROUND The central nervous system (CNS) is a rare site for upper tract urothelial carcinoma (UTUC) metastasis and typically carries a poor prognosis. Little is known about effective treatments. This report describes a 64-year-old man with UTUC with brain and leptomeningeal metastases. He was treated with multiple lines of chemotherapy, immunotherapy, surgery, radiation, and intrathecal methotrexate as part of multimodal therapy delivered through multidisciplinary care. CASE REPORT A 64-year-old man with multiple sclerosis was diagnosed with UTUC. Initial management included a nephroureterectomy followed by platinum-based chemotherapy. Despite this treatment, his malignancy recurred with pulmonary metastases, treated with enfortumab vedotin and local ablation. After this treatment, he achieved systemic disease control. However, he later presented with neurologic symptoms, and imaging showed brain metastases. He underwent resection followed by stereotactic radiation therapy and immunotherapy. Even with this multimodal treatment, he developed leptomeningeal spread, evidenced by cytology-positive cerebrospinal fluid (CSF). Following progression on multiple systemic therapies, he received intrathecal methotrexate with temporary clearance of tumor cells from his CSF before disease progression. This treatment course, including chemotherapy, immunotherapy, and intrathecal methotrexate, prolonged the patient's life before he unfortunately died from his disease. CONCLUSIONS This case report outlines a treatment approach for a rare complication of UTUC. This regimen includes both standard-of-care therapy and inventive strategies extrapolated from data on other solid tumors. Additionally, it contributes to the limited data on the management of CNS metastasis in rare solid tumor malignancies, which could inform future clinical decision-making.

Capnocytophaga canimorsus is a slow-growing, Gram-negative bacterium commonly found as a part of the normal oral flora of dogs and cats, and it is associated with severe systemic infections following dog bites, especially in immunocompromised patients. Although spondylodiscitis due to Capnocytophaga species has been reported in the literature, cases involving previously operated spinal segments are extremely rare. A 52-year-old woman working as a dog trainer presented with fever, headache, photophobia, and lumbar back pain. Her medical history included an L5-S1 hemilaminectomy performed 9-year prior to admission. Following an initial concern for meningitis, imaging studies revealed L4-L5 spondylodiscitis. Microbiological diagnosis was obtained through computed tomography-guided biopsy. Biopsy cultures isolated C. canimorsus after 72 h of anaerobic incubation, subsequently confirmed by MALDI-TOF mass spectrometry and 16S rRNA gene sequencing. The patient was successfully treated with amoxicillin/clavulanic acid, achieving complete resolution of symptoms. Hematogenous seeding, rather than direct surgical site contamination, should be emphasized in patients with a history of prior spinal surgery. Furthermore, C. canimorsus should be included in the differential diagnosis of spinal infections in patients with animal exposure, even in the absence of overt bite wounds.