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Search Results (276)

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Keywords = white-matter lesions

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17 pages, 2624 KiB  
Article
Cerebral Hemodynamics as a Diagnostic Bridge Between Mild Cognitive Impairment and Late-Life Depression: A Multimodal Approach Using Transcranial Doppler and MRI
by Sergiu-Florin Arnautu, Diana-Aurora Arnautu, Minodora Andor, Cristina Vacarescu, Dragos Cozma, Brenda-Cristina Bernad, Catalin Juratu, Adrian Tutelca and Catalin-Dragos Jianu
Life 2025, 15(8), 1246; https://doi.org/10.3390/life15081246 - 6 Aug 2025
Abstract
Background: Vascular dysfunction is increasingly recognized as a shared contributor to both cognitive impairment and late-life depression (LLD). However, the combined diagnostic value of cerebral hemodynamics, neuroimaging markers, and neuropsychological outcomes remains underexplored. This study aimed to investigate the associations be-tween transcranial Doppler [...] Read more.
Background: Vascular dysfunction is increasingly recognized as a shared contributor to both cognitive impairment and late-life depression (LLD). However, the combined diagnostic value of cerebral hemodynamics, neuroimaging markers, and neuropsychological outcomes remains underexplored. This study aimed to investigate the associations be-tween transcranial Doppler (TCD) ultrasound parameters, cognitive performance, and depressive symptoms in older adults with mild cognitive impairment (MCI) and LLD. Importantly, we evaluated the integrative value of TCD-derived indices alongside MRI-confirmed white matter lesions (WMLs) and standardized neurocognitive and affective assessments. Methods: In this cross-sectional study, 96 older adults were enrolled including 78 cognitively unimpaired individuals and 18 with MCI. All participants underwent structured clinical, neuropsychological, and imaging evaluations including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS-15), MRI-based Fazekas scoring of WMLs, and TCD ultrasonography of the middle cerebral artery. Hemodynamic variables included mean blood flow velocity (MBFV), end-diastolic velocity (EDV), pulsatility index (PI), and resistive index (RI). Logistic regression and receiver operating characteristic (ROC) analyses were used to identify independent predictors of MCI. Results: Participants with MCI showed significantly lower MBFV and EDV, and higher PI and RI (p < 0.05 for all) compared with cognitively unimpaired participants. In multivariate analysis, lower MBFV (OR = 0.64, p = 0.02) and EDV (OR = 0.70, p = 0.03), and higher PI (OR = 3.2, p < 0.01) and RI (OR = 1.9, p < 0.01) remained independently associated with MCI. ROC analysis revealed excellent discriminative performance for RI (AUC = 0.919) and MBFV (AUC = 0.879). Furthermore, PI correlated positively with depressive symptom severity, while RI was inversely related to the GDS-15 scores. Conclusions: Our findings underscore the diagnostic utility of TCD-derived hemodynamic parameters—particularly RI and MBFV—in identifying early vascular contributions to cognitive and affective dysfunction in older adults. The integration of TCD with MRI-confirmed WML assessment and standardized cognitive/mood measures represents a novel and clinically practical multi-modal approach for neurovascular profiling in aging populations. Full article
(This article belongs to the Special Issue Intracerebral Hemorrhage: Advances and Perspectives)
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11 pages, 217 KiB  
Article
Brain Injury Patterns and Short-TermOutcomes in Late Preterm Infants Treated with Hypothermia for Hypoxic Ischemic Encephalopathy
by Aslihan Kose Cetinkaya, Fatma Nur Sari, Avni Merter Keceli, Mustafa Senol Akin, Seyma Butun Turk, Omer Ertekin and Evrim Alyamac Dizdar
Children 2025, 12(8), 1012; https://doi.org/10.3390/children12081012 - 31 Jul 2025
Viewed by 225
Abstract
Background: Hypoxic–ischemic encephalopathy (HIE) is a leading cause of severe neurological impairments in childhood. Therapeutic hypothermia (TH) is both safe and effective in neonates born at ≥36 weeks gestation with moderate to severe HIE. We aimed to evaluate short-term outcomes—including brain injury detected [...] Read more.
Background: Hypoxic–ischemic encephalopathy (HIE) is a leading cause of severe neurological impairments in childhood. Therapeutic hypothermia (TH) is both safe and effective in neonates born at ≥36 weeks gestation with moderate to severe HIE. We aimed to evaluate short-term outcomes—including brain injury detected on magnetic resonance imaging (MRI)—in infants born at 34–35 weeks of gestation drawing on our clinical experience with neonates under 36 weeks of gestational age (GA). Methods: In this retrospective cohort study, 20 preterm infants with a GA of 34 to 35 weeks and a matched cohort of 80 infants with a GA of ≥36 weeks who were diagnosed with moderate to severe HIE and underwent TH were included. Infants were matched in a 1:4 ratio based on the worst base deficit in blood gas and sex. Maternal and neonatal characteristics, brain MRI findings and short term outcomes were compared. Results: Infants with a GA of 34–35 weeks had a lower birth weight and a higher rate of caesarean delivery (both p < 0.001). Apgar scores, sex, intubation rate in delivery room, blood gas pH, base deficit and lactate were comparable between the groups. Compared to infants born at ≥36 weeks of GA, preterm neonates were more likely to receive inotropes, had a longer time to achieve full enteral feeding, and experienced a longer hospital stay. The mortality rate was 10% in the 34–35 weeks GA group. Neuroimaging revealed injury in 66.7% of infants born at 34–35 weeks of gestation and in 58.8% of those born at ≥36 weeks (p = 0.56). Injury was observed across multiple brain regions, with white matter being the most frequently affected in the 34–35 weeks GA group. Thalamic and cerebellar abnormal signal intensity or diffusion restriction, punctate white matter lesions, and diffusion restriction in the corpus callosum and optic radiations were more frequently detected in infants born at 34–35 weeks of gestation. Conclusions: Our study contributes to the growing body of literature suggesting that TH may be feasible and tolerated in late preterm infants. Larger randomized controlled trials focused on this vulnerable population are necessary to establish clear guidelines regarding the safety and efficacy of TH in late preterm infants. Full article
(This article belongs to the Section Pediatric Neonatology)
14 pages, 2036 KiB  
Article
Differences in Cerebral Small Vessel Disease Magnetic Resonance Imaging Depending on Cardiovascular Risk Factors: A Retrospective Cross-Sectional Study
by Marta Ribera-Zabaco, Carlos Laredo, Emma Muñoz-Moreno, Andrea Cabero-Arnold, Irene Rosa-Batlle, Inés Bartolomé-Arenas, Sergio Amaro, Ángel Chamorro and Salvatore Rudilosso
Brain Sci. 2025, 15(8), 804; https://doi.org/10.3390/brainsci15080804 - 28 Jul 2025
Viewed by 216
Abstract
Background: Vascular risk factors (VRFs) are known to influence cerebral small vessel disease (cSVD) burden and progression. However, their specific impact on the presence and distribution of each cSVD imaging marker (white matter hyperintensity [WMH], perivascular spaces [PVSs], lacunes, and cerebral microbleeds [...] Read more.
Background: Vascular risk factors (VRFs) are known to influence cerebral small vessel disease (cSVD) burden and progression. However, their specific impact on the presence and distribution of each cSVD imaging marker (white matter hyperintensity [WMH], perivascular spaces [PVSs], lacunes, and cerebral microbleeds [CMBs]) and their spatial distribution remains unclear. Methods: We conducted a retrospective analysis of 93 patients with lacunar stroke with a standardized investigational magnetic resonance imaging protocol using a 3T scanner. WMH and PVSs were segmented semi-automatically, and lacunes and CMBs were manually segmented. We assessed the univariable associations of four common VRFs (hypertension, hyperlipidemia, diabetes, and smoking) with the load of each cSVD marker. Then, we assessed the independent associations of these VRFs in multivariable regression models adjusted for age and sex. Spatial lesion patterns were explored with regional volumetric comparisons using Pearson’s coefficient analysis, which was adjusted for multiple comparisons, and by visually examining heatmap lesion distributions. Results: Hypertension was the VRF that exhibited stronger associations with the cSVD markers in the univariable analysis. In the multivariable analysis, only lacunes (p = 0.009) and PVSs in the basal ganglia (p = 0.014) and white matter (p = 0.016) were still associated with hypertension. In the regional analysis, hypertension showed a higher WMH load in deep structures and white matter, particularly in the posterior periventricular regions. In patients with hyperlipidemia, WMH was preferentially found in hippocampal regions. Conclusions: Hypertension was confirmed to be the VRF with the most impact on cSVD load, especially for lacunes and PVSs, while the lesion topography was variable for each VRF. These findings shed light on the complexity of cSVD expression in relation to factors detrimental to vascular health. Full article
(This article belongs to the Section Neurosurgery and Neuroanatomy)
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23 pages, 1580 KiB  
Article
Elucidating White Matter Contributions to the Cognitive Architecture of Affective Prosody Recognition: Evidence from Right Hemisphere Stroke
by Meyra S. Jackson, Yuto Uchida, Shannon M. Sheppard, Kenichi Oishi, Ciprian Crainiceanu, Argye E. Hillis and Alexandra Z. Durfee
Brain Sci. 2025, 15(7), 769; https://doi.org/10.3390/brainsci15070769 - 19 Jul 2025
Viewed by 378
Abstract
Background/Objectives: Successful discourse relies not only on linguistic but also on prosodic information. Difficulty recognizing emotion conveyed through prosody (receptive affective aprosodia) following right hemisphere stroke (RHS) significantly disrupts communication participation and personal relationships. Growing evidence suggests that damage to white matter [...] Read more.
Background/Objectives: Successful discourse relies not only on linguistic but also on prosodic information. Difficulty recognizing emotion conveyed through prosody (receptive affective aprosodia) following right hemisphere stroke (RHS) significantly disrupts communication participation and personal relationships. Growing evidence suggests that damage to white matter in addition to gray matter structures impairs affective prosody recognition. The current study investigates lesion–symptom associations in receptive affective aprosodia during RHS recovery by assessing whether disruptions in distinct white matter structures impact different underlying affective prosody recognition skills. Methods: Twenty-eight adults with RHS underwent neuroimaging and behavioral testing at acute, subacute, and chronic timepoints. Fifty-seven healthy matched controls completed the same behavioral testing, which comprised tasks targeting affective prosody recognition and underlying perceptual, cognitive, and linguistic skills. Linear mixed-effects models and multivariable linear regression were used to assess behavioral performance recovery and lesion–symptom associations. Results: Controls outperformed RHS participants on behavioral tasks earlier in recovery, and RHS participants’ affective prosody recognition significantly improved from acute to chronic testing. Affective prosody and emotional facial expression recognition were affected by external capsule and inferior fronto-occipital fasciculus lesions while sagittal stratum lesions impacted prosodic feature recognition. Accessing semantic representations of emotions implicated the superior longitudinal fasciculus. Conclusions: These findings replicate previously observed associations between right white matter tracts and affective prosody recognition and further identify lesion–symptom associations of underlying prosodic recognition skills throughout recovery. Investigation into prosody’s behavioral components and how they are affected by injury can help further intervention development and planning. Full article
(This article belongs to the Special Issue Language, Communication and the Brain—2nd Edition)
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18 pages, 6324 KiB  
Article
The Value of Structural Neuroimaging in First-Episode Psychosis and the Prevalence of Imaging Abnormalities and Clinical Relevance: A Real-World Observational Study
by José Pablo Martínez Barbero, José Tortosa Cámara, Beatriz Ramos Barbosa, Paula María Jiménez Gutiérrez, Manuel González Díez, José Eduardo Muñoz Negro, José Prados and Antonio Jesús Láinez Ramos-Bossini
J. Clin. Med. 2025, 14(14), 4925; https://doi.org/10.3390/jcm14144925 - 11 Jul 2025
Viewed by 538
Abstract
Introduction: The usefulness of neuroimaging in patients with first-episode psychosis (FEP) remains controversial. The aim of this study was to assess the prevalence and types of structural abnormalities on neuroimaging in patients with FEP and identify the most frequently used imaging modalities [...] Read more.
Introduction: The usefulness of neuroimaging in patients with first-episode psychosis (FEP) remains controversial. The aim of this study was to assess the prevalence and types of structural abnormalities on neuroimaging in patients with FEP and identify the most frequently used imaging modalities in a real-world setting. Methodology: A retrospective observational study based on a consecutive series of patients admitted to our institution with FEP was conducted. We analyzed the imaging tests performed, the presence of specific lesions, the degree of cortical atrophy (Global Cortical Atrophy, GCA scale), medial temporal atrophy (Medial Temporal lobe Atrophy, MTA scale) and non-specific white matter lesions (Fazekas scale). Descriptive and bivariate analyses were performed according to previously established age cut-offs. Results: A total of 105 patients were included (median age: 36 years; 52.4% men). The most frequently used neuroimaging test was computed tomography (CT) (92.4%). GCA scores that were out of the age range were found in 32.4% of patients, being more frequent in those older than 65 years (p < 0.001). Out-of-range MTA scores were found in 36.2% of patients, especially in patients older than 75 years (p < 0.001). Out-of-range Fazekas scores were found in 4.3% of patients, especially in patients older than 70 years (p = 0.157). Finally, only one specific structural lesion (right frontal cavernoma) was identified in one patient (1%). Overall, at least one non-age-matched abnormality was found in 46.7% of patients. Conclusions: Although non-specific alterations not in accordance with age exist in a significant percentage of patients with FEP, the prevalence of specific lesions is very low. This suggests that neuroimaging tests could be restricted in patients with FEP, especially CT, due to the risks associated with ionizing radiation. However, further prospective and controlled studies are needed to validate our results. Full article
(This article belongs to the Special Issue Clinical Features and Management of Psychosis)
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27 pages, 1801 KiB  
Review
The Future of PET Imaging in Multiple Sclerosis: Characterisation of Individual White Matter Lesions
by Chris W. J. van der Weijden, Jan F. Meilof, Anouk van der Hoorn, Erik F. J. de Vries and Wia Baron
J. Clin. Med. 2025, 14(13), 4439; https://doi.org/10.3390/jcm14134439 - 23 Jun 2025
Viewed by 884
Abstract
Multiple sclerosis (MS) is a multifaceted inflammatory, demyelinating, and neurodegenerative disease typified by lesions with distinct hallmarks in the central nervous system. Dysregulation of micro-environmental factors, including extracellular matrix (ECM) remodelling and glial cell activation, has a decisive effect on lesion development and [...] Read more.
Multiple sclerosis (MS) is a multifaceted inflammatory, demyelinating, and neurodegenerative disease typified by lesions with distinct hallmarks in the central nervous system. Dysregulation of micro-environmental factors, including extracellular matrix (ECM) remodelling and glial cell activation, has a decisive effect on lesion development and disease progression. Understanding the biological and pathological features of lesions would aid in prognosis and personalised treatment decision making. Positron emission tomography (PET) is an imaging technique that uses radio-labelled tracers to detect specific biological phenomena. Recent PET hardware developments enable high-resolution, quantitative imaging, which may allow biological characterisation of relatively small MS lesions. PET may complement MRI by offering objective, quantitative insights into lesion characteristics, including myelin density, inflammation and axonal integrity. Moreover, PET may provide information on lesion traits supporting decision making on upcoming therapeutic strategies for progressive MS, such as the availability of oligodendrocyte progenitor cells and ECM composition that affect remyelination and/or axon regeneration. This review explores the cellular and molecular ECM signatures and neuropathological processes of white matter MS lesions, discusses current and potential novel PET targets that may help characterise MS lesions in vivo, and addresses the potential of PET as a decision tool for selection and evaluation of therapeutic strategies, with a focus on remyelination. Full article
(This article belongs to the Special Issue Recent Advancements in Nuclear Medicine and Radiology)
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8 pages, 194 KiB  
Communication
Neurodevelopmental Outcomes in Children with Neonatal Parechovirus CNS Infections
by Anna Piwowarczyk, Julia Śladowska, Agata Lipiec, Ernest Kuchar and Elżbieta Stawicka
Pathogens 2025, 14(6), 600; https://doi.org/10.3390/pathogens14060600 - 18 Jun 2025
Viewed by 465
Abstract
Human parechoviruses, officially known as Parechovirus A (PeV-A), are more frequently reported as a significant cause of serious infections in newborns and young infants. We aimed to describe the clinical features and neurological outcomes of PeV-A encephalitis cases identified in Warsaw. Infants with [...] Read more.
Human parechoviruses, officially known as Parechovirus A (PeV-A), are more frequently reported as a significant cause of serious infections in newborns and young infants. We aimed to describe the clinical features and neurological outcomes of PeV-A encephalitis cases identified in Warsaw. Infants with suspected encephalitis were retrospectively identified in three hospitals in the summer of 2022. Cases of confirmed PeV-A infection had their comprehensive demographic, clinical, laboratory, imaging, and outcome data reviewed. The psychomotor development of the children up to the age of 2 years was assessed by using the standardized tools. We identified 18 cases of confirmed encephalitis with a PeV-A infection. Their median age was 16 days. Fourteen cases were included in the analysis, while one patient dropped out after the first visit. Most were boys (9/14), and one patient was born preterm. Three patients had white matter alterations on brain MRI at discharge. No significant neurologic sequelae were observed after acute illness. At the 24-month follow-up, based on the Bayley Scales of Infant and Toddler Development (BSID-IV) and the Brunet–Lézine Scale, the children showed no neurodevelopmental sequelae. Brain MRIs were obtained in all of the participants up to 12 months of age and revealed no significant lesions. Neurodevelopmental complications are not frequent in children after PeV-A encephalitis at 24 months of age. Continued follow-up in larger cohorts is needed to explore the predictors of long-term morbidity. Full article
8 pages, 1946 KiB  
Interesting Images
Opercular Perivascular Space Mimicking a Space-Occupying Brain Lesion: A Short Case Series
by Roberts Tumelkans, Cenk Eraslan and Arturs Balodis
Diagnostics 2025, 15(12), 1486; https://doi.org/10.3390/diagnostics15121486 - 11 Jun 2025
Viewed by 505
Abstract
A newly recognized fourth type of perivascular space has recently been described in the radiological literature. Despite its growing relevance, many radiologists are still unfamiliar with its imaging characteristics, often leading to misinterpretation as cystic neoplasms. Due to its potential for diagnostic confusion, [...] Read more.
A newly recognized fourth type of perivascular space has recently been described in the radiological literature. Despite its growing relevance, many radiologists are still unfamiliar with its imaging characteristics, often leading to misinterpretation as cystic neoplasms. Due to its potential for diagnostic confusion, further studies are necessary—particularly those incorporating high-quality imaging examples across various presentations—to facilitate accurate recognition and classification. Perivascular spaces (PVSs) of the brain are cystic, fluid-filled structures formed by the pia mater and located alongside cerebral blood vessels, particularly penetrating arterioles, venules, and capillaries. Under normal conditions, these spaces are small (typically <2 mm in diameter), but in rare instances, they may become markedly enlarged (>15 mm), exerting a mass effect on adjacent brain tissue. This newly identified fourth type of PVS is found in association with the M2 and M3 segments of the middle cerebral artery, typically within the anterior temporal lobe white matter. It may mimic low-grade cystic tumors on imaging due to its size and frequent presence of surrounding perifocal edema. We present two adult male patients with this rare PVS variant. The first patient, a 63-year-old, had a brain magnetic resonance imaging scan (MRI) that revealed a cystic lesion in the white matter of the right temporal lobe anterior pole, near the middle cerebral artery M2 segment, with perifocal vasogenic edema. The second patient, a 67-year-old, had a brain MRI that showed a cystic lesion in the white matter and subcortical region of the right temporal lobe anterior pole, with minimal surrounding gliosis or minimal edema. The cystic lesions in both patients remained unchanged over time on follow-up MRI. These cases illustrate the radiological complexity of this under-recognized entity and emphasize the importance of differential diagnosis to avoid unnecessary intervention. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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22 pages, 1274 KiB  
Review
The Role of MRI Lesions in Identifying Secondary Progressive Multiple Sclerosis: A Comprehensive Review
by Robert-Constantin Anicăi, Alin Ciubotaru, Cristina Grosu, Daniel Alexa, Roxana Covali, Ioana Păvăleanu, Andrei Ionuț Cucu, Amelian Mădălin Bobu, Cristina Mihaela Ghiciuc, Maria Magdalena Leon, Alexandra Maștaleru and Emilian Bogdan Ignat
J. Clin. Med. 2025, 14(12), 4114; https://doi.org/10.3390/jcm14124114 - 10 Jun 2025
Viewed by 787
Abstract
Secondary Progressive Multiple Sclerosis (SPMS) represents a challenging phase of multiple sclerosis, marked by gradual neurological decline and reduced inflammatory activity. In recent years, magnetic resonance imaging (MRI) has become essential for characterizing the neurodegenerative changes underlying SPMS, including white and gray matter [...] Read more.
Secondary Progressive Multiple Sclerosis (SPMS) represents a challenging phase of multiple sclerosis, marked by gradual neurological decline and reduced inflammatory activity. In recent years, magnetic resonance imaging (MRI) has become essential for characterizing the neurodegenerative changes underlying SPMS, including white and gray matter damage, brain atrophy, slowly expanding lesions, and iron rim lesions. This narrative review aims to synthesize the current knowledge on established and emerging MRI biomarkers relevant to SPMS, with a particular focus on their diagnostic, prognostic, and therapeutic implications. This review discusses key themes, such as the shift from inflammatory to neurodegenerative mechanisms, the role of advanced imaging techniques, and the limitations of conventional MRI in detecting smoldering disease. In doing so, it identifies current gaps in evidence, including the need for standardized imaging protocols and large-scale longitudinal studies. A clearer understanding and application of MRI biomarkers may facilitate earlier diagnosis, more tailored treatment strategies, and improved outcomes in patients with SPMS. Full article
(This article belongs to the Special Issue Multiple Sclerosis: Clinical Advances in Diagnosis and Treatment)
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16 pages, 2372 KiB  
Article
Cognitive Functioning in Toxic Oil Syndrome Survivors: A Case-Control Study Four Decades After the Epidemic
by José Lapeña-Motilva, Mariano Ruiz-Ortiz, Glen M. Doniger, María Antonia Nogales, Verónica Giménez de Bejar, Sonia Álvarez-Sesmero, Montserrat Morales, Fernando Bartolomé, Carolina Alquézar, Durjoy Lahiri, Cecilia García-Cena and Julián Benito-León
J. Clin. Med. 2025, 14(11), 3746; https://doi.org/10.3390/jcm14113746 - 27 May 2025
Viewed by 436
Abstract
Background: Toxic oil syndrome (TOS) was a major food-borne epidemic that occurred in Spain in May 1981, caused by the ingestion of rapeseed oil adulterated with aniline. While the somatic sequelae of TOS have been well documented, its long-term cognitive consequences remain poorly [...] Read more.
Background: Toxic oil syndrome (TOS) was a major food-borne epidemic that occurred in Spain in May 1981, caused by the ingestion of rapeseed oil adulterated with aniline. While the somatic sequelae of TOS have been well documented, its long-term cognitive consequences remain poorly understood more than four decades after exposure. Methods: In this case-control study, 50 individuals with clinically confirmed TOS were compared to 50 healthy controls matched for age, sex, and education. All participants completed a comprehensive neuropsychological assessment, along with questionnaires evaluating fatigue, anxiety, depression, and health-related quality of life. Multivariate regression models were adjusted for demographic and vascular risk factors, as well as for mood symptoms, fatigue, and use of central nervous system-acting medications. Structural equation modeling was used to explore the potential mediating effects of affective and fatigue symptoms on cognitive performance. Results: TOS survivors showed significantly poorer performance than controls in attention, executive function, processing speed, and global cognition after adjusting for demographic and vascular risk factors. However, these differences were no longer statistically significant after additional adjustment for fatigue, depression, anxiety, and central nervous system-acting medications. Structural equation modeling analyses revealed that affective symptoms—particularly fatigue—substantially mediated the relationship between TOS and cognitive performance. Conclusions: The cognitive profile observed mirrors that of disorders characterized by subcortical dysfunction and impaired neural connectivity, such as multiple sclerosis and vascular cognitive impairment. Although early postmortem studies in TOS did not demonstrate overt white matter lesions, our findings raise the possibility of long-lasting alterations involving both white and gray matter networks. These results emphasize the need to consider mood and fatigue symptoms when evaluating cognition in TOS survivors and point to the potential for widespread, enduring neurobiological effects stemming from the original toxic exposure. Full article
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10 pages, 230 KiB  
Article
Cardiac Edema Is Associated with White Matter Hyperintensities in Patients with Inflammatory Arthritides: A Combined Brain/Heart MRI Study
by George Markousis-Mavrogenis, Aliki Venetsanopoulou, Ioannis Ntalas, Ioannis Pagounis, Christina Naka, Dionisis Toliopoulos, Dimitrios Apostolou, Paraskevi Voulgari and Sophie I. Mavrogeni
J. Clin. Med. 2025, 14(11), 3726; https://doi.org/10.3390/jcm14113726 - 26 May 2025
Viewed by 503
Abstract
Background: Inflammatory arthritides (IAs) are systemic inflammatory syndromes that can affect diverse body tissues. Central nervous system involvement has been reported, but is considered rare. We investigated the relationship between cardiac and subclinical brain involvement in patients with IAs. Methods: We [...] Read more.
Background: Inflammatory arthritides (IAs) are systemic inflammatory syndromes that can affect diverse body tissues. Central nervous system involvement has been reported, but is considered rare. We investigated the relationship between cardiac and subclinical brain involvement in patients with IAs. Methods: We consecutively enrolled 25 patients with IAs and 31 as disease controls with non-autoimmune cardiovascular diseases (CVDs) reporting cardiac symptoms. Each participant underwent combined brain/heart magnetic resonance imaging (MRI). We also recruited 25 consecutive asymptomatic healthy controls without CVDs who underwent brain MRI. MRI scans were performed on a 1.5 T system. We investigated cardiac function/tissue characterization and the presence/localization of white matter hyperintensities (WMHs). Results: All groups had similar ages (p = 0.267), and 16 (64%) patients with IAs vs. 7 (23%) disease controls vs. 16 (64%) healthy controls were women (p = 0.001). WMHs were detected in ≥1 brain area in 15 (60%) patients with IAs and 16 (53%) disease controls (p = 0.620). WMHs were significantly less prevalent amongst healthy controls [two (8%)] compared to patients with IAs (p < 0.001). Amongst patients with IAs, an increased cardiac T2 ratio was associated with an increased probability of WMH occurrence [OR per 0.1 unit change (95% CI): 1.29 (1.05–1.59), p = 0.016], while a higher cardiac T2 ratio (per 0.1 unit change) and extracellular volume fraction (ECV) were associated with higher WMH lesion burdens [β (95% CI): 0.12 (0.03–0.20), p = 0.008 and 0.25 (0.00–0.49), p = 0.049, respectively]. Conclusions: Patients with IAs and cardiac symptoms had significantly higher subclinical WMH burdens compared to age/sex-matched healthy controls. Myocardial edema was associated with a greater WMH burden, potentially suggesting shared pathophysiologic substrates. Full article
(This article belongs to the Special Issue Clinical Advances in Cardio-Rheumatology)
14 pages, 14167 KiB  
Article
Laser-Induced Cortical Lesions in Mice as a Model for Progressive Multiple Sclerosis Pathology
by Bhavya Ojha, Bita Ramazani, Rouhin Belal, Jonathan Krieger, Maria Bloksgaard, Gabriela Teresa Lyszczarz, Dominika Rusin, Agnieszka Wlodarczyk, Una FitzGerald, Trevor Owens and Reza Khorooshi
Biomedicines 2025, 13(5), 1195; https://doi.org/10.3390/biomedicines13051195 - 14 May 2025
Viewed by 628
Abstract
Background: The current animal models of multiple sclerosis (MS) predominantly emphasize white matter inflammation, reflecting early-stage disease. However, progressive MS (PMS) is characterized by cortical pathology, including subpial demyelination, chronic meningeal inflammation, and microglial activation, which are underrepresented in the existing models. While [...] Read more.
Background: The current animal models of multiple sclerosis (MS) predominantly emphasize white matter inflammation, reflecting early-stage disease. However, progressive MS (PMS) is characterized by cortical pathology, including subpial demyelination, chronic meningeal inflammation, and microglial activation, which are underrepresented in the existing models. While alternative mouse models replicate the relapsing–remitting phenotype and gray matter pathology, pathology is frequently dispersed throughout the brain, complicating the analysis of the specific lesion sites. Methods: To address this gap, we developed a novel model that integrates laser-induced focal demyelination with cytokine-driven meningeal inflammation to replicate the key aspects of PMS cortical pathology. Results: Using two-photon laser irradiation, we induced controlled subpial cortical lesions in CX3CR1-GFP mice, leading to microglial activation, astrocytosis, and focal demyelination. The addition of IFNγ-expressing adenovirus to promote meningeal inflammation which resulted in prolonged glial responses, increased immune cell infiltration, and exacerbated demyelination, mimicking the PMS-associated pathology. Conclusions: This model provides a powerful tool to investigate the mechanisms underlying the cortical lesion development and immune-mediated neurodegeneration in PMS. By capturing the critical aspects of cortical pathology, it enables the evaluation of therapeutic strategies targeting neuroinflammation and demyelination, ultimately aiding in the development of new treatments of progression in PMS patients. Full article
(This article belongs to the Special Issue Multiple Sclerosis: Diagnosis and Treatment—3rd Edition)
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32 pages, 432 KiB  
Systematic Review
Functional and Structural Alterations in Pediatric Multiple Sclerosis: A Systematic Review and a Preliminary Activation Likelihood Estimation Functional Magnetic Resonance Imaging Meta-Analysis
by Nicoletta Cera, Joana Pinto and Ricardo Faustino
Pediatr. Rep. 2025, 17(3), 57; https://doi.org/10.3390/pediatric17030057 - 13 May 2025
Viewed by 705
Abstract
Background/Objectives: Pediatric multiple sclerosis (MS) is a rare and complex neuroinflammatory disease characterized by demyelination and neurological dysfunction in individuals under 18 years of age. This systematic review and activation likelihood estimation (ALE) meta-analysis aimed to synthesize the existing literature on functional and [...] Read more.
Background/Objectives: Pediatric multiple sclerosis (MS) is a rare and complex neuroinflammatory disease characterized by demyelination and neurological dysfunction in individuals under 18 years of age. This systematic review and activation likelihood estimation (ALE) meta-analysis aimed to synthesize the existing literature on functional and structural brain alterations in pediatric MS patients. Methods: Following the PRISMA guidelines, we analyzed 21 studies involving 917 pediatric MS patients and 320 healthy controls, assessing brain structure and function using MRI and fMRI techniques. Results: The results reveal consistent alterations in brain regions critical for cognitive and motor functions, including reduced brain volume, increased lesion load, and disrupted functional connectivity, particularly in the thalamus, cerebellum, and hippocampus. The ALE meta-analysis identified significant activation clusters in the dorsal anterior cingulate cortex, angular gyrus, and superior parietal lobes, regions associated with cognition, attention, and working memory. Conclusions: These findings suggest that pediatric MS uniquely affects brain development, contributing to cognitive impairments that differ from those observed in adult MS. Our study underscores the importance of early diagnosis and tailored therapeutic interventions to mitigate neurodevelopmental disruptions and improve long-term outcomes in pediatric MS patients. Full article
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17 pages, 5071 KiB  
Article
The Effect of Tumor Necrosis Factor-α and Interleu-Kin-1β on the Restorative Properties of Human Oligodendrocyte Precursor Cells In Vitro
by Zhaoyan Wang, Ying He, Qian Wang, Weipeng Liu, Yinxiang Yang, Haipeng Zhou, Xuexia Ma, Caiyan Hu, Zuo Luan and Suqing Qu
Bioengineering 2025, 12(5), 457; https://doi.org/10.3390/bioengineering12050457 - 25 Apr 2025
Viewed by 486
Abstract
Premature white matter injury (PWMI) represents the principal form of brain injury in preterm infants, and effective therapies remain elusive. Transplantation of oligodendrocyte precursor cells (OPCs) emerges as a potential treatment for PWMI, yet the injury-induced inflammatory response may impact these cells’ functionality. [...] Read more.
Premature white matter injury (PWMI) represents the principal form of brain injury in preterm infants, and effective therapies remain elusive. Transplantation of oligodendrocyte precursor cells (OPCs) emerges as a potential treatment for PWMI, yet the injury-induced inflammatory response may impact these cells’ functionality. To date, no studies have explored the influence of inflammatory factors on the functionality of human (h) OPCs. The predominant inflammatory cytokines identified in PWMI lesions are tumor necrosis factor (TNF)-α and interleukin (IL)-1β. This study investigates the impact of these cytokines on hOPC migration, proliferation, and differentiation using the human adult neural stem cell amplification and differentiation system in vitro. Results indicate that IL-1β significantly impedes hOPC migration, while both TNF-α and IL-1β hinder proliferation and differentiation. In summary, inflammatory factors overexpressed following PWMI impede OPCs from realizing their regenerative potential. These findings underscore the necessity of modulating the post-PWMI inflammatory milieu to enhance the efficacy of transplanted cells concerning migration, proliferation, and differentiation. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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15 pages, 2084 KiB  
Review
The Dark Side of Cardiac and Aortic Interventions: Unveiling Cerebral Microbleeds with Susceptibility-Weighted Imaging
by Tommaso Casseri, Maria Giulia Maccaglia, Ivano Lombardo, Andrea Bianchi, Rosaria Tartarone, Giorgio Busto, Andrea Ginestroni, Sara Speziali, Walter Dorigo and Enrico Fainardi
J. Vasc. Dis. 2025, 4(2), 16; https://doi.org/10.3390/jvd4020016 - 7 Apr 2025
Viewed by 640
Abstract
Cerebral microbleeds (CMBs) are increasingly detected in patients with aortic and cardiac diseases following transcatheter aortic valve implantation (TAVI), thoracic endovascular aortic repair (TEVAR), or cardiac surgery. CMBs can be observed in magnetic resonance imaging (MRI) when susceptibility-weighted imaging (SWI) or T2*-Gradient-Echo (GRE) [...] Read more.
Cerebral microbleeds (CMBs) are increasingly detected in patients with aortic and cardiac diseases following transcatheter aortic valve implantation (TAVI), thoracic endovascular aortic repair (TEVAR), or cardiac surgery. CMBs can be observed in magnetic resonance imaging (MRI) when susceptibility-weighted imaging (SWI) or T2*-Gradient-Echo (GRE) sequences are used. Differential diagnosis of CMBs from other causes, such as cerebral amyloid angiopathy (CAA), is crucial because of its clinical implications, particularly for anticoagulation management. A literature search was conducted using publicly available online databases to identify relevant studies for this review. The selection criteria focused on publications utilizing MRI with T2*-GRE or SWI sequences to detect CMBs in patients following cardiac or endovascular procedures. The extracted data included study characteristics, lesion distribution, and associated clinical factors. Ten studies were included in this review, with 50% analyzing a prospective cohort. Cerebral T2*-GRE or SWI hypointensities after cardiac and vascular procedures often showed a lobar distribution, thus complicating the differential diagnosis with “probable” CAA. However, CMBs seem predominantly located in subcortical white matter (SWM), unlike CAA, and commonly not associated with other alterations. Furthermore, CMBs seem to correlate with prolonged procedural duration, especially in the case of cardiopulmonary bypass, and anticoagulation therapy. Regarding etiology, various hypotheses have been proposed, with the most widely accepted being microhemorrhagic. CMBs are a common finding following cardiac procedures, either surgical or endovascular. Their distribution patterns may aid in differentiating from CAA-related lesions, with important implications for anticoagulation strategies. Identifying and characterizing these lesions is essential for optimizing postoperative management. Full article
(This article belongs to the Section Neurovascular Diseases)
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