Search Results (11)

Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific to ASD. While grey matter has been the primary focus, white matter (WM) may be more specific in identifying the particular biological signature of the neurodiversity of ASD. Diffusion tensor imaging (DTI) is the more appropriate tool to investigate WM in ASD. Despite being introduced in 1994, its application to ASD research began in 2001. Studies employing DTI identify altered fractional anisotropy (FA), mean diffusivity, and radial diffusivity (RD) in individuals with ASD compared to typically developing (TD) individuals. Methods: We systematically reviewed literature on 21 May 2025 on PubMed using the following strategy: (“autism spectrum”[ti] OR autistic[ti] OR ASD[ti] OR “high-functioning autism” OR Asperger*[ti] OR Rett*[ti]) AND (DTI[ti] OR “diffusion tensor”[ti] OR multimodal[ti] OR “white matter”[ti] OR tractograph*[ti]). Our search yielded 239 results, of which 26 were adult human studies and eligible. Results: Analysing the evidence, we obtained regionally diverse WM alterations in adult ASD, specifically in FA, MD, RD, axial diffusivity and kurtosis, neurite density, and orientation dispersion index, compared to TD individuals, mostly in frontal and interhemispheric tracts, association fibres, and subcortical projection pathways. These alterations were less prominent than those of children and adolescents, indicating that individuals with ASD may improve during brain maturation. Conclusions: Our findings suggest that white matter alterations in adults with ASD are regionally diverse but generally less pronounced than in younger populations. This may indicate a potential improvement or adaptation of brain structure during maturation. Further research is needed to clarify the neurobiological mechanisms underlying these changes and their implications for clinical outcomes. Full article

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

Background: In cases of intracranial meningiomas invading into surrounding tissues, determining the resection boundary can be challenging and often makes complete resection difficult. In such situations, the introduction of novel intraoperative techniques to identify infiltrative tumor components is desirable to improve the extent of tumor resection. Methods: A prospective clinical study was conducted on patients with intracranial meningiomas suspected of infiltration into the surrounding tissues. After completing the tumor resection under conventional white-light microscopy, intraoperative fluorescence diagnosis using 5-aminolevulinic acid (5-ALA) was performed to determine whether additional resection of the unintended residual tumor was feasible. Results: Intraoperative fluorescence diagnosis enabled additional resection of the residual tumor in 38.5% of the 13 enrolled cases and 45.5% of the 11 cases in which the tumor exhibited fluorescence positivity. Among the additional resected specimens, tumor infiltration was observed in all fluorescence-positive lesions of the bone and dura mater, whereas tumor cells were detected in only 33.3% of the fluorescence-positive areas in the adjacent brain parenchyma. Conclusions: Intraoperative fluorescence diagnosis using 5-ALA enhanced the extent of the resection of invasive meningiomas. Future large-scale studies are warranted to determine whether 5-ALA fluorescence diagnosis contributes to reducing tumor recurrence and improving overall survival in patients with invasive intracranial meningiomas. Full article

The purpose of this study was to examine the relationship between demyelination and cellular reactions in the cerebellum of Canine Distemper Virus (CDV)-infected dogs. We subdivided the disease staging by adding the degree of demyelination determined by Luxol Fast Blue staining to the previously reported disease staging from the acute stage to the chronic stage, and investigated the relationship between demyelination in the cerebellum and the number and histological changes in astroglia, microglia, and Purkinje cells in each stage. Reactions of astrocytes and microglia were observed at an early stage when demyelination was not evident. Changes progressed with demyelination. Demyelination initially began in the medulla adjoining the fourth ventricle and gradually spread to the entire cerebellum, including the lobes. CDV immune-positive granules were seen from the early stage, and inclusion bodies also appeared at the same time. CDV immune-positive reaction and inclusion bodies were observed in astrocytes, microglia, neurons, ependymal cells, and even leptomeningeal mononuclear cells. On the other hand, infiltration of CDV-immunoreactive particles from the pia mater to the gray matter and further into the white matter through the granular layer was observed from an early stage. Purkinje cells decreased from the intermediate stage, and a decrease in cells in the granular layer was also observed. There was no clear association between age and each stage, and the stages did not progress with age. Full article

Alzheimer’s disease (AD) is characterized by complex interactions between neuropathological markers, metabolic dysregulation, and structural brain changes. In this study, we utilized a multimodal approach, combining immunohistochemistry, functional metabolic mapping, and microstructure sensitive diffusion MRI (dMRI) to progressively investigate these interactions in the 5xFAD mouse model of AD. Our analysis revealed age-dependent and region-specific accumulation of key AD markers, including amyloid-beta (Aβ), GFAP, and IBA1, with significant differences observed between the hippocampal formation and upper and lower regions of the cortex by 6 months of age. Functional metabolic mapping validated localized disruptions in energy metabolism, with glucose hypometabolism in the hippocampus and impaired astrocytic metabolism in the cortex. Notably, increased cortical glutaminolysis suggested a shift in microglial metabolism, reflecting an adaptive response to neuroinflammatory processes. While dMRI showed no significant microstructural differences between 5xFAD and wild-type controls, the study highlights the importance of metabolic alterations as critical events in AD pathology. These findings emphasize the need for targeted therapeutic strategies addressing specific metabolic disturbances and underscore the potential of integrating advanced imaging with metabolic and molecular analyses to advance our understanding of AD progression. Full article

Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) plays a vital role in a large number of neuronal processes underlying learning and memory, which are known to be disrupted in schizophrenia. However, Lingo-1 has never been examined in the context of schizophrenia. The genetic association of a single-nucleotide polymorphism (SNP, rs3144) and methylation (CpG sites) in the Lingo-1 3′-UTR region was examined, with the testing of cognitive dysfunction and white matter (WM) integrity in a schizophrenia case-control cohort (n = 268/group). A large subset of subjects (97 control and 161 schizophrenia subjects) underwent structural magnetic resonance imaging (MRI) brain scans to assess WM integrity. Frequency of the rs3144 minor allele was overrepresented in the schizophrenia population (p = 0.03), with an odds ratio of 1.39 (95% CI 1.016–1.901). CpG sites surrounding rs3144 were hypermethylated in the control population (p = 0.032) compared to the schizophrenia group. rs3144 genotype was predictive of membership to a subclass of schizophrenia subjects with generalized cognitive deficits (p < 0.05), in addition to having associations with WM integrity (p = 0.018). This is the first study reporting a potential implication of genetic and epigenetic risk factors in Lingo-1 in schizophrenia. Both of these genetic and epigenetic alterations may also have associations with cognitive dysfunction and WM integrity in the context of the schizophrenia pathophysiology. Full article

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that presents a largely unknown etiopathology. The presence of reactive astrocytes in MS lesions has been described for a long time; however, the role that these cells play in the pathophysiology of MS is still not fully understood. Recently, we used an MS animal model to perform high-throughput sequencing of astrocytes’ transcriptome during disease progression. Our data show that astrocytes isolated from the cerebellum (a brain region typically affected in MS) showed a strong alteration in the genes that encode for proteins related to several metabolic pathways. Specifically, we found a significant increase in glycogen degradation, glycolytic, and TCA cycle enzymes. Together with these alterations, we detected an upregulation of genes that characterize “astrocyte reactivity”. Additionally, at each disease time point we also reconstructed the morphology of cerebellum astrocytes in non-induced controls and in EAE animals, near lesion regions and in the normal-appearing white mater (NAWM). We found that near lesions, astrocytes presented increased length and complexity compared to control astrocytes, while no significant alterations were observed in the NAWM. How these metabolic alterations are linked with disease progression is yet to be uncovered. Herein, we bring to the literature the hypothesis of performing metabolic reprogramming as a novel therapeutic approach in MS. Full article

This paper presents the results of non-invasive diagnostic investigations performed on the canvas oil painting depicting the Marian iconography “Mater Boni Consilii”. The painting, whose author and origin are unknown, was found in an old shop in Florence following the overflowing of the Arno River in 1966. In order to define the importance of the artwork, a multianalytical analysis was performed on the painting, using multispectral imaging, X-ray fluorescence (XRF), and Fourier Transform Infrared Spectroscopy (FTIR-ATR) for the definition of materials, with a particular focus on the identification of pigments. The results allowed for the drawing up of a color palette, composed mainly of ochre and earth pigments, cinnabar, lithopone, lead white, and ultramarine pigments. After cross-referencing the acquired information with other findings, it was possible to place the painting in the period between the end of the XIXth and the beginning of the XXth centuries. Full article

A stroke may be followed by central post-stroke pain (CPSP), which is characterized by chronic neuropathic pain. The exact mechanism has not yet been fully uncovered. We investigated alterations in the white matters in patients with CPSP, compared with stroke patients without CPSP and normal controls. Our retrospective cross-sectional, case-control study participants were assigned to three groups: CPSP (stroke patients with CPSP (n = 17)); stroke control (stroke patients without CPSP (n = 26)); and normal control (normal subjects (n = 34)). The investigation of white matter for CPSP was focused on the values of fiber numbers (FN) and fractional anisotrophy (FA) for spinothalamic tract (STT), anterior thalamic radiation (ATR), superior thalamic radiation (STR) and posterior thalamic radiation (PTR), and corticospinal tract (CST) was measured. The FA for the STT and STR of the CPSP group were lower than those for the stroke control and normal control groups. The FA of CST and ATR did not differ between the CPSP and stroke groups, but both differed from the normal control. The FA of PTR in the stroke control group differed from the normal control group, but not from the CPSP group. The FN of CST, STT, ATR, and STR for the CPSP and stroke control groups did not differ from each other, but both differed from those of normal controls. FN of PTR did not differ between the CPSP and normal control groups. The alterations in the spinothalamic tract and superior thalamic radiation after stroke would play a role in the pathogenesis of CPSP. Full article

For biomedical applications, superparamagnetic nanoparticles (MNPs) have to be coated with a stealth layer that provides colloidal stability in biological media, long enough persistence and circulation times for reaching the expected medical aims, and anchor sites for further attachment of bioactive agents. One of such stealth molecules designed and synthesized by us, poly(polyethylene glycol methacrylate-co-acrylic acid) referred to as P(PEGMA-AA), was demonstrated to make MNPs reasonably resistant to cell internalization, and be an excellent candidate for magnetic hyperthermia treatments in addition to possessing the necessary colloidal stability under physiological conditions (Illés et al. J. Magn. Magn. Mater. 2018, 451, 710–720). In the present work, we elaborated on the molecular background of the formation of the P(PEGMA-AA)-coated MNPs, and of their remarkable colloidal stability and salt tolerance by using potentiometric acid–base titration, adsorption isotherm determination, infrared spectroscopy (FT-IR ATR), dynamic light scattering, and electrokinetic potential determination methods. The P(PEGMA-AA)@MNPs have excellent blood compatibility as demonstrated in blood sedimentation, smears, and white blood cell viability experiments. In addition, blood serum proteins formed a protein corona, protecting the particles against aggregation (found in dynamic light scattering and electrokinetic potential measurements). Our novel particles also proved to be promising candidates for MRI diagnosis, exhibiting one of the highest values of r2 relaxivity (451 mM⁻¹s⁻¹) found in literature. Full article

Our lab has previously demonstrated that multiple sclerosis-induced spinal cord white matter damage and motor deficits are mediated by the pathological disruption of zinc homeostasis. Abnormal vesicular zinc release and intracellular zinc accumulation may mediate several steps in the pathophysiological processes of multiple sclerosis (MS), such as matrix metallopeptidase 9 (MMP-9) activation, blood-brain barrier (BBB) disruption, and subsequent immune cell infiltration from peripheral systems. Oral administration of a zinc chelator decreased BBB disruption, immune cell infiltration, and spinal white matter myelin destruction. Therefore, we hypothesized that zinc released into the extracellular space during MS progression is involved in destruction of the myelin sheath in spinal cord white mater and in generation of motor deficits. To confirm our previous study, we employed zinc transporter 3 (ZnT3) knockout mice to test whether vesicular zinc depletion shows protective effects on multiple sclerosis-induced white matter damage and motor deficits. ZnT3 gene deletion profoundly reduced the daily clinical score of experimental autoimmune encephalomyelitis (EAE) by suppression of inflammation and demyelination in the spinal cord. ZnT3 gene deletion also remarkably inhibited formation of multiple sclerosis-associated aberrant synaptic zinc patches, MMP-9 activation, and BBB disruption. These two studies strongly support our hypothesis that zinc release from presynaptic terminals may be involved in multiple sclerosis pathogenesis. Further studies will no doubt continue to add mechanistic detail to this process and with luck, clarify how these observations may lead to development of novel therapeutic approaches for the treatment of multiple sclerosis. Full article