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10 pages, 1307 KB  
Review
Seronegative Immune-Mediated Cerebellar Ataxia in Children: Autoimmune Encephalitis Spectrum Disorder or a Distinct Entity?
by Gontika Maria, Tsimakidi Chrysanthi, Salamou Eudokia, Prattos Theofanis, Kallias Nikolaos, Kilidireas Constantinos, Tzartos John and Gkougka Dionysia
Children 2025, 12(11), 1513; https://doi.org/10.3390/children12111513 - 8 Nov 2025
Viewed by 159
Abstract
Pediatric seronegative immune-mediated cerebellar ataxia (IMCA) remains a poorly defined and often under-recognized diagnosis, particularly in young children, where symptoms are frequently misattributed to self-limited post-infectious processes. We report the case of a 2.5-year-old girl who presented with acute-onset ataxia (mSARA score: 14). [...] Read more.
Pediatric seronegative immune-mediated cerebellar ataxia (IMCA) remains a poorly defined and often under-recognized diagnosis, particularly in young children, where symptoms are frequently misattributed to self-limited post-infectious processes. We report the case of a 2.5-year-old girl who presented with acute-onset ataxia (mSARA score: 14). Cerebrospinal fluid analysis revealed pleocytosis and positive oligoclonal bands, while serial brain imaging and extensive autoantibody panels were unremarkable. However, indirect immunohistochemistry (TIIF/IHC) demonstrated a positive intracellular signal in cerebellar Purkinje cells, supporting the diagnosis of isolated seronegative IMCA. The patient showed sustained clinical improvement with prolonged corticosteroid therapy (mSARA score: 1). To date, only a few similar cases have been reported in the literature. It remains unclear whether these presentations fall within the spectrum of autoimmune encephalitis (AIE) or represent a distinct pediatric phenotype, potentially expanding the age range of primary autoimmune cerebellar ataxia previously described in adults. We recommend incorporating TIIF/IHC into the diagnostic workup of both isolated and combined pediatric cerebellar ataxia syndromes to support diagnosis and guide individualized treatment. Additionally, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are emerging as promising biomarkers in this context and warrant further investigation. Full article
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13 pages, 393 KB  
Article
Seroprevalence of Tick-Borne Encephalitis Virus in Latvia Using Standard and Subtype-Specific NS1-Based ELISA Assays
by Zane Freimane, Gerhard Dobler, Guntis Karelis, Lidia Chitimia-Dobler, Oksana Savicka and Dace Zavadska
Pathogens 2025, 14(11), 1115; https://doi.org/10.3390/pathogens14111115 - 2 Nov 2025
Viewed by 335
Abstract
Background: Latvia is one of the most endemic tick-borne encephalitis (TBE) countries in Europe. However, assessing TBE seroprevalence and true infection rates has been challenging. Current diagnostics cannot reliably distinguish between immune responses induced by natural infection from those induced by vaccination, especially [...] Read more.
Background: Latvia is one of the most endemic tick-borne encephalitis (TBE) countries in Europe. However, assessing TBE seroprevalence and true infection rates has been challenging. Current diagnostics cannot reliably distinguish between immune responses induced by natural infection from those induced by vaccination, especially in TBE endemic countries with recommended immunisation programmes. A recently developed ELISA targeting antibodies against TBEV non-structural protein 1 (NS1) offers improved specificity for natural infection and can differentiate among three clinically relevant TBEV subtypes. Methods: We conducted a cross-sectional TBEV seroprevalence study in the Latvian population during 2019–2022, consisting of two pools: 1020 residents living in different regions of Latvia and 200 random Latvian Biobank blood samples. We used the standard anti-TBEV IgG ELISA (VIDITEST, VIDIA, Czech Republic) for the screening and detection of TBEV (whole virus) IgG antibodies and the newly established research-use anti-TBEV NS1 IgG ELISA for the detection of subtype-specific TBEV NS1 IgG antibodies against three virus subtypes: European, Siberian and Far Eastern. Results: The total TBEV seroprevalence among 1020 residents was 39.7%, representing all age cohorts of the population from all regions of Latvia. In total, 33.4% of the enrolled population were vaccinated against TBE with at least one dose of the TBE vaccine. Among the unvaccinated population, 16.3% had positive TBEV-specific IgG antibodies by standard ELISA. On the contrary, NS1-specific antibodies, indicating past natural infection, were detected in only 4.3% of the overall study population. Subtype differentiation revealed infections from all three major TBEV subtypes present in Latvia. Conclusions: In conclusion, this population-based study highlights a high risk of TBE in Latvia, with substantial seroprevalence even among unvaccinated individuals. The NS1-based ELISA enhances the accuracy of TBE surveillance and offers important clinical utility by facilitating more reliable diagnosis and case classification, regardless of vaccination status. Full article
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17 pages, 1443 KB  
Article
Bayesian Estimation of the True Prevalence of Caprine Arthritis Encephalitis in Hungarian Goat Herds
by Krisztina Bárdos, Marietta Máté, Katalin Veres, Zsolt Lang, Giuseppe Bertoni, Carlos Eduardo Abril, Snorre Stuen, Saulius Petkevičius, Marcin Mickiewicz, Michał Czopowicz, Jarosław Kaba and László Ózsvári
Viruses 2025, 17(11), 1455; https://doi.org/10.3390/v17111455 - 31 Oct 2025
Viewed by 357
Abstract
Background: Caprine arthritis encephalitis (CAE) is a major viral disease of goats, caused by small ruminant lentivirus (SRLV), associated with chronic arthritis, mastitis, pneumonia, and encephalitis, leading to economic losses and reduced animal welfare. This study aimed to estimate the true prevalence of [...] Read more.
Background: Caprine arthritis encephalitis (CAE) is a major viral disease of goats, caused by small ruminant lentivirus (SRLV), associated with chronic arthritis, mastitis, pneumonia, and encephalitis, leading to economic losses and reduced animal welfare. This study aimed to estimate the true prevalence of CAE in Hungarian goat herds, based on nationwide sampling and statistical modeling. Methods: Blood samples from 1218 goats in 53 herds were tested using ELISA, and true prevalence was estimated by Bayesian analysis. Results: The mean herd true prevalence (HTP) was 29.1% (95% CrI: 20.8–38.5%), while within the infected herds, the conditional within herd prevalence (CWHP) reached 58% ± 27.1%. Medium- and large-sized herds (>50 animals) showed the highest mean HTP (77.8% and 74.9%, respectively). No significant regional differences were observed, indicating that CAE is uniformly distributed across the country. Conclusions: Our findings place Hungary among moderately to highly affected European countries and highlight the need for a nationwide control strategy integrating routine serological surveillance, biosecurity improvements, farmer education, and long-term tools such as selective breeding. Full article
(This article belongs to the Special Issue Viral Diseases of Sheep and Goats)
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14 pages, 778 KB  
Review
Fast-Track to Protection? A Review of Encepur’s Express Dosing Schedule for Tick-Borne Encephalitis
by Kyra Zens, Ralph Torgler, Michael Horn and Carsten Schade Larsen
Viruses 2025, 17(11), 1439; https://doi.org/10.3390/v17111439 - 29 Oct 2025
Viewed by 525
Abstract
Cases of confirmed tick-borne encephalitis (TBE) have increased dramatically over the last 30 years, highlighting growing endemicity across Eurasia. Two preventative vaccines, Encepur® (Bavarian Nordic A/S, Hellerup, Denmark) and FSME-Immun® (Pfizer Ireland Pharmaceuticals, Cork, Ireland), are licensed in Europe. For both [...] Read more.
Cases of confirmed tick-borne encephalitis (TBE) have increased dramatically over the last 30 years, highlighting growing endemicity across Eurasia. Two preventative vaccines, Encepur® (Bavarian Nordic A/S, Hellerup, Denmark) and FSME-Immun® (Pfizer Ireland Pharmaceuticals, Cork, Ireland), are licensed in Europe. For both vaccines, primary immunisation consists of a three-dose regimen, administered over approximately one year using “Conventional” dosing schedules. Both vaccines can also be administered using “Rapid” schedules, which shorten the interval between the first two doses but still take around a year to complete. Currently, only Encepur offers an approved “Express” schedule, whereby all three priming doses are given within 21 days. The effectiveness of TBE vaccination is markedly higher in individuals who receive ≥3 doses, compared with those who receive only one or two doses, indicating the importance of series completion. Moreover, seropositivity takes several weeks to develop after vaccination. As such, individuals are advised to initiate vaccination before peak tick season to allow sufficient time to develop protective immunity during periods of highest risk. Despite these considerations, vaccine uptake and series completion remain suboptimal in TBE-endemic regions. Furthermore, many vaccinees—including travellers with limited time before departure and residents of endemic areas—do not initiate vaccination until peak tick season, when risk is greatest. Broader use of Encepur’s Express schedule may help to address these challenges. The Express schedule’s 21-day timeframe may help to increase series completion by reducing drop-offs associated with prolonged dosing intervals. Additionally, it can support timely protection by enabling series completion, with sufficient time post-vaccination to develop protective immunity, all within a single-risk season, even among late initiators. In this narrative review, we evaluate the safety and immunogenicity of Encepur’s Express schedule and discuss its potential utility across a broader range of vaccinees. These insights may help inform TBE vaccine recommendations and support efforts towards improving vaccination strategies amid increasing TBE risk. Full article
(This article belongs to the Section Invertebrate Viruses)
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11 pages, 231 KB  
Article
Complications of Therapeutic Plasma Exchange in Pediatric Neuroimmune Disorders
by Kathrin Eichinger, Markus Breu, Marleen Renken, Sandy Siegert, Elisa Hilz, Sarah Glatter, Dagmar Csaicsich, Michael Boehm, Christian Lechner, Barbara Kornek and Rainer Seidl
Children 2025, 12(11), 1457; https://doi.org/10.3390/children12111457 - 27 Oct 2025
Viewed by 347
Abstract
Background: Therapeutic plasma exchange (TPE) is an established treatment for immune-mediated neurological diseases in adults, but pediatric-specific data remain limited. This retrospective single-center study investigates the safety, complication profile, and clinical outcomes of TPE in children with pediatric neuroimmunological disorders (PNID). Methods: Medical [...] Read more.
Background: Therapeutic plasma exchange (TPE) is an established treatment for immune-mediated neurological diseases in adults, but pediatric-specific data remain limited. This retrospective single-center study investigates the safety, complication profile, and clinical outcomes of TPE in children with pediatric neuroimmunological disorders (PNID). Methods: Medical records of pediatric patients who underwent TPE at the Medical University of Vienna between April 2006 and October 2022 were reviewed. Inclusion criteria required TPE initiation before the age of 18 years. Data collected included diagnoses, pre-TPE therapy, TPE characteristics, complications and clinical outcomes based on retrospective documentation. Results: A total of 53 patients (60% female, median age 13 years) were included and underwent 378 TPE procedures. Most common diagnoses were pediatric-onset multiple sclerosis (23%) and autoimmune encephalitis (19%). TPE was preceded by corticosteroids and/or intravenous immunoglobulin in 83% of patients. Complications occurred in 81% of patients and 23% of procedures and were predominantly rated mild to moderate (CTCAE I–II), including nausea, hypotension, and catheter-related issues. Severe complications (CTCAE III–IV) occurred in 11% of patients; no deaths were reported. Clinical improvement was documented in 84% of patients, with 42% showing significant improvement. Conclusions: TPE is a generally well-tolerated and effective treatment in PNID, with a high rate of clinical improvement and predominantly mild complications. The higher reported complication rate compared to other studies likely reflects more comprehensive documentation of minor adverse events. These findings support the use of TPE in PNID, particularly in cases refractory to first-line therapies. Standardized reporting of outcomes and complications is essential to improve comparability across studies and guide future clinical practice. Full article
(This article belongs to the Special Issue Recent Advances in Pediatric-Onset Multiple Sclerosis)
10 pages, 213 KB  
Brief Report
Standardized Diagnostic Assays for Omsk Hemorrhagic Fever Virus
by Jeong-Hyun Lee, Sunyoung Jung, Hwajung Yi and Yoon-Seok Chung
Pathogens 2025, 14(11), 1093; https://doi.org/10.3390/pathogens14111093 - 27 Oct 2025
Viewed by 617
Abstract
Omsk hemorrhagic fever is an acute zoonotic disease caused by Omsk hemorrhagic fever virus, a member of the genus Flavivirus (family Flaviviridae), with a reported case-fatality rate of approximately 3%. Historically confined to southwestern Siberia, ecological changes raise concerns about possible spread to [...] Read more.
Omsk hemorrhagic fever is an acute zoonotic disease caused by Omsk hemorrhagic fever virus, a member of the genus Flavivirus (family Flaviviridae), with a reported case-fatality rate of approximately 3%. Historically confined to southwestern Siberia, ecological changes raise concerns about possible spread to non-endemic regions. Although no Omsk hemorrhagic fever cases have been reported in the Republic of Korea, the risk of accidental importation highlights the importance of establishing a reliable diagnostic protocol. We established and validated an institutionally developed diagnostic protocol employing real-time reverse transcription polymerase chain reaction targeting the NS2A and C genes of Omsk hemorrhagic fever virus. Primers and probes were designed from all available genomes to ensure broad strain coverage. Human ribonuclease P was used as an internal control to verify nucleic acid extraction and amplification. Using synthetic deoxyribonucleic acid fragments and in vitro-transcribed ribonucleic acid, assay performance was optimized, and analytical sensitivity was determined using probit analysis. The limits of detection were 74.50 copies/µL (threshold cycle 32.99) for NS2A and 70.41 copies/µL (threshold cycle 35.38) for C. Specificity testing using representative flaviviruses (West Nile virus, Yellow fever virus, Zika virus, St. Louis encephalitis virus, and Tick-borne encephalitis virus) and an alphavirus (Venezuelan equine encephalitis virus) demonstrated no cross-reactivity. The assay demonstrated high sensitivity, specificity, and reproducibility, supporting its potential application in national and international Omsk hemorrhagic fever virus surveillance systems. Full article
11 pages, 941 KB  
Article
Unraveling the Burden of Viral and Bacterial Central Nervous System Infections: A Two-Year Retrospective Study
by Nabeel Alzahrani, Ahmed Alshehri, Ali Alshehri and Sameera Al Johani
Diagnostics 2025, 15(21), 2699; https://doi.org/10.3390/diagnostics15212699 - 24 Oct 2025
Viewed by 391
Abstract
Background/Objectives: Central nervous system (CNS) infections remain a significant public health challenge and require rapid and accurate diagnosis to guide clinical management. Although the incidence of bacterial meningitis has declined owing to widespread vaccination, viral etiologies continue to dominate CNS infections. The aim [...] Read more.
Background/Objectives: Central nervous system (CNS) infections remain a significant public health challenge and require rapid and accurate diagnosis to guide clinical management. Although the incidence of bacterial meningitis has declined owing to widespread vaccination, viral etiologies continue to dominate CNS infections. The aim of this study was to assess the epidemiological trends, age distribution, and seasonality of CNS infections using multiplex PCR. Methods: A retrospective analysis was conducted on cerebrospinal fluid (CSF) samples collected between January 2021 and December 2022 from patients with CNS infections at King Abdulaziz Medical City. A BioFire FilmArray Meningitis/Encephalitis (ME) panel was used to detect pathogens. Patient demographics, pathogen distribution, and seasonal trends were analyzed. Results: A total of 2460 CSF samples were tested, of which 130 (5%) were positive for at least one pathogen. Viral pathogens accounted for 82.3% of the infections, with human herpesvirus-6 (HHV-6) (31%) and enterovirus (EV) (20%) being the most common. Bacterial pathogens represented 17.7% of the cases, with Streptococcus pneumoniae (6%) and Escherichia coli K1 (5%) being the predominant bacterial agents. The highest infection burden was observed in infants aged 0–6 months, with a marked male predominance. Seasonal analysis revealed multiple peaks in viral infections, particularly of HHV-6 and EVs, whereas bacterial infections were sporadic, with Streptococcus agalactiae and Streptococcus pneumoniae peaking in October and November. Conclusions: Viral infections, particularly HHV-6 and EVs, dominated CNS infections, with distinct seasonal and age-related variations. These findings underscore the value of multiplex PCR in improving the rapid diagnosis of CNS infections and aiding in timely treatment and antimicrobial stewardship. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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7 pages, 471 KB  
Case Report
Acute Sulcal FLAIR Hyperintensity in Severe Tick-Borne Encephalitis: A Potential Prognostic Marker
by Vincent Böhm, Bogdan-Andrei Ianosi, Caterina Kulyk, Franz Gruber, Maria Lorenz, Thomas Mitterling, Amadeus Hauser, Stephan Eger, Ulrike Köhl, Serge Weis, Sibylle Wimmer, Michael Sonnberger and Raimund Helbok
Life 2025, 15(11), 1655; https://doi.org/10.3390/life15111655 - 23 Oct 2025
Viewed by 398
Abstract
(1) Background: To report two cases of severe tick-borne encephalitis (TBE) in elderly patients presenting with a previously undescribed subarachnoid T2/FLAIR hyperintensity on repeated MRI examinations, which may serve as an early imaging biomarker of disease severity. (2) Methods: Two unvaccinated 82-year-old patients [...] Read more.
(1) Background: To report two cases of severe tick-borne encephalitis (TBE) in elderly patients presenting with a previously undescribed subarachnoid T2/FLAIR hyperintensity on repeated MRI examinations, which may serve as an early imaging biomarker of disease severity. (2) Methods: Two unvaccinated 82-year-old patients (one male and one female) presented with acute encephalitis and required intensive care. Serial brain MRI, EEG, CSF analysis, and neurophysiological assessments were performed. (3) Results: Both patients showed rapid progressive neurological deterioration in the context of TBE, confirmed by elevated serum and CSF IgM and IgG titers. Early follow-up MRI revealed striking sulcal hyperintensities on T2/FLAIR sequences, interpreted as protein-rich subarachnoid inflammatory changes. These changes paralleled clinical worsening and resolved on follow-up imaging. The male patient developed meningoencephalomyeloradiculitis, remained comatose, and died from respiratory failure (the brain and spinal cord were examined postmortem). The female patient had meningoencephaloradiculitis with severe dysphagia and was discharged with a modified Rankin Scale score of four. Both patients demonstrated epileptiform EEG activity. The CSF analysis revealed markedly elevated total protein, lactate, tau protein, and CXCL13, as evidence of blood–brain barrier disruption and inflammatory neurodegeneration. (4) Conclusions: We describe acute subarachnoid T2/FLAIR hyperintensity in TBE as an imaging feature that may correlate with severe systemic inflammation and a poor prognosis. This radiological finding could serve as a potential early prognostic marker in TBE. Full article
(This article belongs to the Special Issue Encephalitis: From Molecular Pathophysiology to Therapy)
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11 pages, 581 KB  
Article
The Evaluation of a Rapid Syndromic Multiplex Meningitis/Encephalitis RT-qPCR MX-17 Panel
by Naim Mahroum, Meltem Yashar, Feyza Nihal Ugur, Nefise Zulal Oz, Gozde Ulfer, Ayse Istanbullu Tosun and Mesut Yilmaz
Diagnostics 2025, 15(20), 2629; https://doi.org/10.3390/diagnostics15202629 - 17 Oct 2025
Viewed by 723
Abstract
Background/Objectives: Meningoencephalitis (ME) is a life-threatening infectious disease; therefore, prompt and accurate diagnosis is lifesaving. Traditional diagnostic methods, such as culture, have several limitations related to sensitivity and specificity. Emerging multiplex ME-PCR panels are a comprehensive and rapid tool in a single [...] Read more.
Background/Objectives: Meningoencephalitis (ME) is a life-threatening infectious disease; therefore, prompt and accurate diagnosis is lifesaving. Traditional diagnostic methods, such as culture, have several limitations related to sensitivity and specificity. Emerging multiplex ME-PCR panels are a comprehensive and rapid tool in a single test. The Bio-Speedy Meningitis/Encephalitis RT-qPCR MX-17 panel (Bioeksen R&D Technologies Inc., Turkey) enables testing for 17 targets. To evaluate the performance of the panel compared to clinical and CSF parameters. Methods: A total of 403 patients with a preliminary diagnosis of ME were reviewed between January 2019 and September 2023. Following revision, 72 patients with clinical, CSF, and laboratory findings were included. The tested panel was used to detect targeted pathogens in CSF samples. The 30-day survival rate and prolonged stay were analyzed. Results: The median CSF protein value was 59.5 mg/dL (14.2–1471 mg/dL) and glucose was 61.95 mg/dL (0.083–165 mg/dL). Forty-one (56.9%) ME panel results were positive, among which 38.9% (28) were viral and 19.4% (14) were bacterial. HHV-6 ranked first with a rate of 15.3%. The Bio-Speedy panel test results outperformed the CSF culture (p < 0.001). The correlation of the Bio-Speedy panel with impaired consciousness was statistically significant (p = 0.004). Six (8.3%) patients from the study group died within 30 days. Conclusions: Compared to traditional methods, Bio-Speedy panel was effective in identifying the causative agents of ME. The Bio-Speedy ME RT-qPCR MX-17 panel offers accurate detection of ME-causing pathogens. The implementation of the panel in clinical practice can impact patient management and improve outcomes. Full article
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10 pages, 1779 KB  
Case Report
Next-Generation Sequencing for Diagnosis of Fatal Balamuthia Amoebic Encephalitis: A Case Report
by Yuanyuan Feng, Huiyu Feng, Xuegao Yu, Jing Zhao, Hongyan Zhou, Jiaoxing Li, Peisong Chen and Li Feng
Diagnostics 2025, 15(20), 2590; https://doi.org/10.3390/diagnostics15202590 - 14 Oct 2025
Viewed by 561
Abstract
Background: Balamuthia mandrillaris is a free-living amoebic parasite that primarily causes rare opportunistic infections in immunocompromised hosts. Balamuthia amoebic encephalitis (BAE) is a rare yet severe parasitic infection affecting the central nervous system. It has an extremely low incidence in China but [...] Read more.
Background: Balamuthia mandrillaris is a free-living amoebic parasite that primarily causes rare opportunistic infections in immunocompromised hosts. Balamuthia amoebic encephalitis (BAE) is a rare yet severe parasitic infection affecting the central nervous system. It has an extremely low incidence in China but can have a mortality rate as high as 98%. The clinical manifestations of amebic infections are similar to those of bacterial and tuberculous meningitis, lacking specificity, which makes accurate diagnosis challenging in the clinical setting. Case Presentation: A 61-year-old immunocompetent woman experienced worsening headache and a moderate fever over the course of five days, initially treated as a common cold. On 25 February 2025, she exhibited behavioral abnormalities, dysphagia, and a high fever of 40.2 °C, which progressed to a coma. On 26 February, her cranial CT scan revealed multifocal hemorrhagic lesions in the right frontotemporoparietal lobes. The MRI revealed similar lesions with slight enhancement and herniation. She underwent an emergency decompressive craniectomy, yet her condition continued to deteriorate following the surgery. On 27 February, serum targeted next-generation sequencing (tNGS) detected B. mandrillaris. Additionally, metagenomic NGS (mNGS) of the cerebrospinal fluid (CSF) sample confirmed the presence on 28 February. Finally, B. mandrillaris was identified through a brain tissue biopsy on 3 March. However, due to the delayed diagnosis and lack of effective drugs, her condition rapidly deteriorated and became irreversible. Her family ultimately chose to withdraw treatment. Conclusions: This study highlights the application of NGS for early diagnosis of patients with severe CNS infection. Both tNGS and mNGS can be considered for the rapid detection of rare or novel pathogens and for facilitating diagnosis. Full article
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17 pages, 1895 KB  
Review
Diffusion Basis Restricted Fraction as a Putative Magnetic Resonance Imaging Marker of Neuroinflammation: Histological Evidence, Diagnostic Accuracy, and Translational Potential
by Szabolcs Kéri
Life 2025, 15(10), 1599; https://doi.org/10.3390/life15101599 - 14 Oct 2025
Cited by 1 | Viewed by 797
Abstract
Diffusion basis spectrum imaging–derived restricted fraction (DBSI-RF) isolates the low apparent diffusion coefficient water signal attributed to cellular crowding. It is therefore proposed as a putative magnetic resonance imaging (MRI) marker of neuroinflammation. The purpose of this narrative review is to evaluate animal [...] Read more.
Diffusion basis spectrum imaging–derived restricted fraction (DBSI-RF) isolates the low apparent diffusion coefficient water signal attributed to cellular crowding. It is therefore proposed as a putative magnetic resonance imaging (MRI) marker of neuroinflammation. The purpose of this narrative review is to evaluate animal and human studies that compared DBSI-RF with histopathological benchmarks and clinical parameters. Across inflammatory demyelination, viral encephalitis, traumatic brain injury, and neurodegenerative disorders, DBSI-RF correlated moderately to strongly with immune cell density and distinguished inflammation from demyelinating or axonal pathology. In acute multiple sclerosis, combined isotropic fractions predicted lesion evolution, clinical subtypes, and deep-learning models that included DBSI-RF classified lesion subtypes with high accuracy. DBSI-RF might also be used to track putative neuroinflammation associated with psychosocial stress, mood disorders, and anxiety disorders. The strengths of the method include sensitivity to subclinical changes and the concurrent mapping of coexisting edema, demyelination, and axon loss. Limitations include non-specific etiology features, a demanding acquisition protocol, and limited large-scale human validation. Overall, DBSI-RF may demonstrate a promising diagnostic and prognostic accuracy, warranting standardized, multicenter, prospective trials and external validation. Full article
(This article belongs to the Section Medical Research)
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15 pages, 2026 KB  
Article
Genomic Characterization of a Novel Yezo Virus Revealed in Ixodes pavlovskyi Tick Virome in Western Siberia
by Maxim Apanasevich, Nikita Dubovitskiy, Anastasiya Derko, Anna Khozyainova, Alexander Tarasov, Alina Kokhanenko, Gleb Artemov, Evgeny Denisov, Alexander Shestopalov and Kirill Sharshov
Viruses 2025, 17(10), 1362; https://doi.org/10.3390/v17101362 - 11 Oct 2025
Viewed by 586
Abstract
Ixodid ticks are blood-sucking ectoparasites of vertebrates. They constitute an integral part of natural foci and are responsible for the worldwide transmission of infections to humans, which can result in severe symptoms. For instance, the Tomsk region, where three abundant tick species ( [...] Read more.
Ixodid ticks are blood-sucking ectoparasites of vertebrates. They constitute an integral part of natural foci and are responsible for the worldwide transmission of infections to humans, which can result in severe symptoms. For instance, the Tomsk region, where three abundant tick species (Dermacentor reticulatus, Ixodes pavlovskyi, I. persulcatus) occur, is an endemic area for tick-borne encephalitis virus (TBEV). An increasing number of novel infectious agents carried by ticks have been identified using metagenomic sequencing. A notable example is the Yezo virus (Orthonairovirus yezoense, YEZV), which was discovered in patients with fever after tick bites in Japan and China between 2014 and 2025. For the first time, we have performed metagenomic sequencing of the virome of ticks collected in the Tomsk region. In a sample obtained from a pool of I. pavlovskyi ticks, all three segments of the YEZV genome were detected. The phylogenetic analysis showed that the newly identified isolate formed a sister group to previously described virus isolates, indicating the presence of a new genetic variant. This study presents the first report of YEZV detection in I. pavlovskyi ticks in the Tomsk region, thereby expanding the geographical range and number of vector species for YEZV and highlighting the importance of monitoring viral agents circulating among ticks in Western Siberia. Full article
(This article belongs to the Special Issue Tick-Borne Viruses: Transmission and Surveillance, 2nd Edition)
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17 pages, 470 KB  
Case Report
Basal Ganglia Involvement in Pediatric Mycoplasma pneumoniae Meningoencephalitis: Two Cases and a Literature Review
by Dominik Ljubas, Luka Švitek, Lorna Stemberger Marić, Nina Krajcar, Maja Vrdoljak Pažur, Ana Tripalo Batoš, Srđan Roglić and Goran Tešović
Epidemiologia 2025, 6(4), 62; https://doi.org/10.3390/epidemiologia6040062 - 10 Oct 2025
Viewed by 577
Abstract
Background: Mycoplasma pneumoniae is a common cause of respiratory tract infections in children, but neurological complications, including encephalitis, are increasingly recognized. Basal ganglia involvement is rare, and a poorly characterized feature of meningoencephalitis, with clinical consequences being inconclusive. Methods: We report two pediatric [...] Read more.
Background: Mycoplasma pneumoniae is a common cause of respiratory tract infections in children, but neurological complications, including encephalitis, are increasingly recognized. Basal ganglia involvement is rare, and a poorly characterized feature of meningoencephalitis, with clinical consequences being inconclusive. Methods: We report two pediatric cases of Mycoplasma pneumoniae-related meningoencephalitis with bilateral basal ganglia lesions seen on MRI. A literature review was conducted using PubMed, Scopus, and Web of Science to identify reports of M. pneumoniae-related meningoencephalitis in children, and related MRI findings. Results: Both patients (12-year-old male and 14-year-old female) presented with acute meningoencephalitis syndrome and had marked mononuclear pleocytosis. In both patients M. pneumoniae was confirmed with serological assay from serum sample, while in one patient M. pneumoniae was also confirmed by PCR from pharyngeal swab. Both exhibited bilateral basal ganglia lesions, with complete regression observed during follow-up. Treatment with corticosteroids led to full recovery in both cases. After a literature search, a total of 21 patients had basal ganglia involvement reported. Conclusions: Literature suggests variable MRI findings in pediatric M. pneumoniae encephalitis, with basal ganglia involvement being uncommon and rarely reported, especially among older children. While diagnostic challenges related to extrapulmonary manifestations of the infection persist, basal ganglia involvement could aid in diagnosis, especially in older children presenting with meningoencephalitis along with pronounced pleocytosis when respiratory symptoms are absent or mild. Full article
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23 pages, 489 KB  
Review
Japanese Encephalitis Vaccine in Low- and Middle-Income Countries (LMICs): A Narrative Review of Efficacy, Effectiveness, Safety, Cost, and Policy
by Eufrasia Ine Pilihanto, Btari Kalisha Nyratri, Muhammad Dafrizal Firdaus and Rano Kurnia Sinuraya
Vaccines 2025, 13(10), 1038; https://doi.org/10.3390/vaccines13101038 - 8 Oct 2025
Viewed by 1288
Abstract
Japanese Encephalitis (JE) is a mosquito-borne viral infection that causes acute brain inflammation. First identified in Japan in 1871, the disease gained renewed global attention in 2025 after emerging in a non-endemic region, raising significant healthcare concerns. Vaccination remains the most effective strategy [...] Read more.
Japanese Encephalitis (JE) is a mosquito-borne viral infection that causes acute brain inflammation. First identified in Japan in 1871, the disease gained renewed global attention in 2025 after emerging in a non-endemic region, raising significant healthcare concerns. Vaccination remains the most effective strategy for preventing outbreaks. However, low- and middle-income countries (LMICs) face considerable challenges in implementing vaccination programs due to geographical, economic, and regulatory barriers. Most existing studies on JE vaccines (JEVs) have been conducted in higher-income countries, leaving critical gaps in data on efficacy and safety in LMIC settings. Furthermore, uncertainties surrounding cost-effectiveness make funding decisions more complex. This narrative review evaluates the current evidence on JE vaccination in LMICs, based on a literature search in PubMed and ScienceDirect covering 2005–2025. The review examines vaccine efficacy, safety, cost-effectiveness, and policy implementation. Findings show that JEVs demonstrate high efficacy and strong safety profiles, with mild adverse effects, most commonly fever. The live attenuated SA 14-14-2 vaccine (LAJEV) is particularly cost-effective, offering substantial economic benefits by reducing healthcare expenditures in endemic regions. To ensure sustainability, vaccination programs in LMICs require tailored policies and targeted financial support. Policy frameworks must be adapted to local contexts, enabling focused, effective, and equitable implementation. Full article
(This article belongs to the Section Vaccines and Public Health)
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Article
Diversity of Hard Ticks (Acari: Ixodidae) Fauna on Green Habitats of Urban Areas in Eastern Croatia
by Stjepan Krčmar, Petra Matak, Lora Krčmar and Kristina Nikolić
Pathogens 2025, 14(10), 1010; https://doi.org/10.3390/pathogens14101010 - 7 Oct 2025
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Abstract
Hard ticks (Acari: Ixodidae) are vectors of numerous pathogenic microorganisms in humans and animals. In Croatia, very few studies have been conducted on the diversity of hard tick fauna in urban green areas. Therefore, the aim of this study was to investigate the [...] Read more.
Hard ticks (Acari: Ixodidae) are vectors of numerous pathogenic microorganisms in humans and animals. In Croatia, very few studies have been conducted on the diversity of hard tick fauna in urban green areas. Therefore, the aim of this study was to investigate the diversity and seasonal dynamics of hard tick fauna in three eastern Croatian cities. Three species of ticks were recorded in Osijek and Vukovar, while six species were recorded in the area of the city of Vinkovci. In total, six species were collected during this study, and together with an earlier record of Ixodes canisuga, seven species are now known from urban green habitats in this region. The most abundant species was I. ricinus (82.06%), followed by R. sanguineus s.l. (9.03%), H. concinna (6.51%), D. reticulatus (1.26%), I. hexagonus (0.91%), D. marginatus (0.11%), and I. canisuga (0.11%). The detection of R. sanguineus s.l. in Vinkovci and Vukovar represents the first record of this species in eastern Croatia. In Osijek and Vinkovci, I. ricinus was the most abundant species. This tick is the primary vector of Lyme disease and tick-borne encephalitis, the two most common tick-borne diseases affecting humans in eastern Croatia. In Osijek and Vukovar, peak abundance of ticks was recorded in May, while in Vinkovci in March. Given that the species documented here represent 30.43% of all tick species recorded in Croatia, their presence in urban areas highlights the potential public health risk associated with ticks in these environments. Full article
(This article belongs to the Special Issue Ticks and Tick-Borne Pathogens in the Balkans)
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