Search Results (212)

Background/Objectives: Occipital defects with dural exposure represent a complex reconstructive challenge requiring reliable vascularized coverage to prevent severe complications. This study aims to describe a salvage reconstructive approach using a transverse cervical artery (TCA)-based inferior trapezius flap and to highlight a technical modification intended to increase flap reach. Methods: We report the case of a 61-year-old male presenting with a chronic occipital defect associated with infection following cerebellar abscess evacuation. After failure of primary closure, skin grafting, and local flap reconstruction, a regional pedicled inferior trapezius musculocutaneous flap was performed. Intraoperatively, the dorsal scapular artery (DSA) was selectively sacrificed after confirmation of dominant TCA perfusion to increase the arc of rotation. Flap perfusion was assessed clinically. Results: The flap provided adequate coverage of the defect with stable perfusion. The postoperative course was favorable, with resolution of a minor donor-site seroma. At 1- and 3-month follow-up, stable coverage, preserved cervical mobility, and satisfactory aesthetic outcomes were observed. These results were maintained at 1-year follow-up, with no functional limitation or late complications. Conclusions: This single case report suggests that a TCA-based inferior trapezius flap may represent a feasible salvage option in selected occipital defects. The intentional sacrifice of the DSA appeared to increase flap reach in this case; however, its safety and reproducibility remain uncertain. Further studies are required before this approach can be routinely recommended. Full article

Background and Objectives: The goal of this study was to evaluate the associations between peripapillary retinal nerve fibre layer (pRNFL) thickness, disability-related clinical measures, including the Expanded Disability Status Scale (EDSS), and report-based magnetic resonance imaging (MRI) findings in patients with multiple sclerosis (MS), and to explore potential longitudinal relationships between pRNFL changes and disability progression. Materials and Methods: A retrospective single-centre study was conducted in patients with MS diagnosed according to the 2010/2017 McDonald criteria at the Neurology Clinic of the Hospital of Lithuanian University of Health Sciences Kauno Klinikos. The study included 84 patients. pRNFL thickness was measured using optical coherence tomography (OCT) at baseline (defined as the time of diagnosis) and, for some patients, follow-up. Associations between pRNFL measures and clinical as well as MRI-derived variables were assessed using Spearman correlation and multivariable linear and ordinal regression analyses. Results: In cross-sectional analyses, lower baseline pRNFL thickness was associated with higher baseline disability (ρ = −0.257, p = 0.019) and greater worsening of EDSS over time (ρ = −0.268, p = 0.013). Significant associations were also observed between thinner pRNFL and pyramidal system impairment and bowel/bladder dysfunction. In adjusted linear regression models, each 20 µm reduction in pRNFL was associated with a 0.46-point increase in EDSS (B = −0.023, SE = 0.009) and a 0.32-point rise in cerebellar functional system score (B = −0.016, SE = 0.006). Among the 45 patients with repeat OCT, exploratory longitudinal pRNFL thinning showed directional trends toward increasing disability; however, these associations were not consistently significant after adjustment. Baseline pRNFL thickness showed a modest association with a composite MRI regional lesion score derived from report-based binary variables. Conclusions: In this real-world retrospective cohort, thinner pRNFL was associated with greater disability in cross-sectional analyses. Associations with individual MRI regions and radiological activity were limited and inconsistent. These findings should be interpreted as preliminary and hypothesis-generating. Further prospective studies are needed to clarify the potential role of OCT-derived pRNFL measurements. Full article

Objectives: Autism spectrum disorder (ASD) is increasingly conceptualized as a neurodevelopmental condition with prenatal origins. Advances in fetal magnetic resonance imaging (MRI), including high-resolution structural imaging and resting-state functional connectivity analysis, now enable in vivo characterization of the developing human brain before birth. This review examines whether fetal MRI biomarkers are associated with later ASD diagnosis or autistic traits. Methods: We conducted a PRISMA-informed narrative review of human studies identified through MEDLINE, EMBASE, SCOPUS, and Web of Science. Eligible studies included original human investigations using fetal MRI to assess brain structure and/or function, with postnatal ASD diagnosis or standardized autistic-trait outcomes. Results: Eight eligible studies provide converging evidence that neurodevelopmental divergence associated with ASD may be detectable in utero. Structural analyses consistently report prenatal volumetric alterations, particularly enlargement of the insular cortex between the second and third trimesters. Additional findings of regional overgrowth and hemispheric asymmetries suggest distributed deviations in cortical maturation. Functional fetal MRI studies further demonstrate atypical large-scale network organization prior to birth. Altered connectivity within cingulate, prefrontal, temporal, and cerebellar circuits has been prospectively associated with later autistic traits, indicating that network-level integration may diverge before behavioral symptoms emerge. Evidence from high-risk conditions, including isolated ventriculomegaly and tuberous sclerosis complex, reinforces the association between prenatal structural abnormalities and increased ASD risk. Conclusions: Current evidence suggests that structural and functional brain alterations identifiable by fetal MRI may precede the clinical manifestation of ASD. These findings support a model of ASD as a condition potentially rooted in prenatal neurodevelopmental divergence. However, larger, standardized, multicenter studies are required before fetal MRI biomarkers can be translated into predictive or clinical applications. Full article

Background: Early-onset Alzheimer’s disease (EOAD) caused by autosomal dominant mutations provides a deterministic framework for investigating genetic modifiers of neurodegeneration. Telomere biology has emerged as a central regulator of genomic stability, cellular ageing, and stress response integration, yet its role in EOAD, particularly in under-represented populations, remains poorly defined. Methods: We conducted a cross-sectional case–control study to evaluate the genetic distribution, disease association, and predicted regulatory consequences of common variants in the telomere maintenance genes TERT and TERC in individuals from Western Mexico. The EOAD group comprised genetically confirmed carriers of the PSEN1 p.Ala431Glu (A431E) founder mutation with clinical EOAD (n = 69), and controls were unrelated individuals without dementia (n = 179). Five common variants were analyzed: rs2242652, rs2853677, rs2736100, and rs10069690 (TERT), and rs12696304 (TERC). Results: Genotype distributions in controls conformed to the Hardy–Weinberg equilibrium. Single-variant analyses showed no significant allele-level associations. Most TERT variants did not show significant allele-level associations with EOAD. However, a preliminary genotype-level enrichment for the GC allele at rs12696304 (TERC) was observed among EOAD cases compared with controls; allele-level associations were not significant. Linkage disequilibrium analysis revealed low r² values (<0.20), supporting variant independence. Population-level allele frequency comparisons revealed ancestry-dependent divergence across loci; in silico functional annotation localised all variants to non-coding regulatory regions. GTEx-based analyses indicated that rs12696304 acts as an eQTL for ACTRT3 in whole blood and pituitary, as well as for LRRC34 in the cerebellar hemisphere, suggesting a potential regulatory network within the TERC locus (3q26.2). Conclusions: Overall, common regulatory variants in TERT did not show strong independent effects on EOAD susceptibility in PSEN1 A431E carriers. However, the convergence of association patterns, functional annotation, and regulatory evidence provides hypothesis-generating support for the TERC locus (3q26.2), particularly rs12696304, as a candidate region for further investigation. Additional studies integrating telomere dynamics, functional validation, and multi-omics analyses are needed to clarify the role of telomere biology in the pathogenesis of autosomal dominant EOAD. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms and widespread alterations in brain networks. Circulating biomarkers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) reflect neuroaxonal damage and astroglial activation, respectively, but their relationship with large-scale brain connectivity remains poorly understood. Seventy-three PD patients and thirty-four healthy controls underwent diffusion magnetic resonance imaging. Whole-brain tractography was used to reconstruct structural connectivity networks, and graph-theoretical measures were derived. Serum NfL and GFAP levels were quantified, and their associations with network metrics and clinical variables were assessed. PD patients showed significant alterations in global and nodal network organization compared to controls. Higher NfL and GFAP levels were associated with reduced global clustering coefficient and efficiency, as well as increased path length and modularity. At the regional level, higher biomarker levels were associated with reduced network measures in the right thalamus and right cerebellar cortex. No significant associations were observed in healthy controls. These findings demonstrate that circulating biomarkers of neurodegeneration are linked to both global and regional disruptions of structural brain connectivity in PD, supporting the integration of blood-based biomarkers and connectomics to better characterize disease-related network alterations. Full article

Novel psychoactive substances (NPSs) exhibit extremely strong pharmaco-toxicological activity, often leading to severe adverse effects that pose a serious risk to consumers’ health. Among these, synthetic cannabinoids (SCs) currently represent the majority of drug seizures in Europe. One such compound, AKB-48 (also known as APINACA), was first identified in Japanese herbal smoking blends in 2012. Although it mimics the effects of Δ9-THC, the primary psychoactive component of Cannabis sativa, AKB-48 can induce more severe and potentially life-threatening outcomes. Several in vivo studies investigating the acute administration of AKB-48 have reported profound behavioral, neurological, and neurochemical alterations, including disruptions of neurotransmission across multiple brain regions, thus confirming its neurotoxic potential. Given the recognized vulnerability of the cerebellum to NPS, and its critical role in integrating neural circuits affected by psychostimulant drugs, the present study evaluated the toxic effects of repeated AKB-48 exposure on the cerebellar cortex of adult male and female ICR-CD1^® mice. Particular attention was paid to the modulation of cell death pathways, alongside assessments of sensorimotor responses. The results demonstrate, for the first time, that repeated AKB-48 administration induces significant morphological, immunohistochemical, and ultrastructural changes in both male and female mice. These alterations included pronounced disruption of cerebellar architecture and marked modulation of cell death pathways, further corroborated by TEM-detected ultrastructural damage and a substantial reduction in the basal visual placing response. Overall, the findings provide clear evidence of AKB-48’s sex-independent neurotoxicity, leading to cerebellar alterations that ultimately result in neuroplasticity impairment. Full article

Bovine spongiform encephalopathy (BSE) is a fatal transmissible spongiform encephalopathy caused by the misfolding of the host prion protein (PrP), representing a unique intersection between molecular pathology, neuroanatomy, and public health regulation. Although historically framed as a single feedborne epizootic, BSE is now recognized as a spectrum of strain-defined prion disorders encompassing classical and atypical forms with distinct origins, neuroanatomical trajectories, and surveillance implications. This review integrates advances in prion biology, neurodegenerative mechanisms, and anatomical pathways of neuroinvasion to reframe BSE as a heterogeneous disease entity. We synthesize evidence on PrP^C structure, trafficking, and proteolytic processing to explain how normal cellular physiology enables strain-specific conversion to pathogenic PrP^Sc and subsequent neurotoxicity. Distinct patterns of neuroinvasion and regional vulnerability are discussed for classical versus atypical (H- and L-type) BSE, highlighting differences in lymphoid involvement, brainstem targeting, and cortical or cerebellar tropism. We further examine how these biological differences translate into diagnostic sensitivity, surveillance design, and zoonotic risk assessment. By integrating molecular strain diversity with neuroanatomical connectivity, this review underscores the limitations of obex-centered surveillance for atypical BSE and emphasizes the need for proportionate yet precautionary monitoring strategies. These considerations should be interpreted in light of surveillance-dependent detection biases, which influence the apparent distribution of BSE forms. Ultimately, BSE emerges as a critical model for understanding how protein misfolding disorders bridge cellular mechanisms, animal health, and human public health policy. Full article

Background: Frequent nocturnal arousals are a core feature of comorbid insomnia and obstructive sleep apnea (COMISA), yet the underlying central mechanisms remain unclear. Identifying brain functional correlates of nocturnal awakenings may help clarify arousal-related mechanisms and inform potential interventional targets. Methods: A total of 99 participants (COMISA, insomnia alone, OSA alone, and healthy controls) underwent clinical assessments, polysomnography, and brain magnetic resonance imaging (MRI). MRI metrics were compared across groups, followed by correlation and regression analyses with the arousal index, adjusting for respiratory events and insomnia-related factors. Results: Patients with COMISA exhibited more severe insomnia symptoms, greater daytime dysfunction, and more frequent nocturnal awakenings than those with insomnia alone, although their arousal index did not differ from that of the OSA group. Patients with COMISA exhibited altered activity in the right cerebellar lobule VIII (Cerebelum_8_R), left middle temporal gyrus, and right inferior frontal gyrus, opercular part. Lower fractional amplitude of low-frequency fluctuations (fALFF) in the Cerebelum_8_R was associated with a higher arousal index. This association remained significant after controlling for insomnia severity and sleep efficiency but was attenuated after adjustment for AHI. Conclusions: Reduced functional activity in the Cerebelum_8_R was independently associated with sleep fragmentation in COMISA, independent of insomnia severity but potentially mediated by respiratory events. These findings suggest this region may be involved in arousal-related neural regulation and could represent a therapeutic target for the complex symptoms of COMISA. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2500095809. Full article

Background/Objectives: This systematic review synthesizes MRI evidence to characterize neuromorphological alterations in somatosensory and vestibular brain regions among adolescents with idiopathic scoliosis (AIS). Methods: This systematic review was conducted in accordance with the PRISMA 2020 guidelines. We systematically searched five databases from inception to January 2026 for case–control MRI studies comparing AIS patients (10–18 years) with healthy controls. Two reviewers independently screened studies, extracted data, and assessed the risk of bias using the Newcastle–Ottawa Scale. Results: Across 15 studies (1270 participants), AIS patients demonstrated consistent neuromorphological alterations: (1) lower cerebellar tonsil position (0.9–2.8 mm below baseline), with ectopia incidence correlating with curve severity; (2) cortical thickening in bilateral medial regions but thinning in left paracentral areas; (3) left-dominant white matter volume increases and impaired microstructure in the corpus callosum; and (4) left-sided vestibular morphological changes, including a more vertical semicircular canal. Conclusions: AIS is associated with consistent neuromorphological alterations in key somatosensory and vestibular regions, supporting a potential neuroanatomical basis for impaired sensorimotor integration in its pathogenesis. It should be noted that substantial heterogeneity among the included studies prevented a meta-analysis, and the cross-sectional design limits causal interpretations Registration: This systematic review was registered in PROSPERO (CRD42024577195). Full article

Background/Objectives: Fetal alcohol spectrum disorders (FASDs) occur in nearly 5% of children in the United States and have been associated with alterations in neurological functions, neuroanatomical changes, and behavioral deficits encompassing an individual’s lifetime. Alterations in myelination have been reported in both rodent models and humans. The cerebellum is a heavily myelinated brain region, and oligodendrocyte and myelination transcripts have been reported to be altered in the cerebellum following early-life ethanol (EtOH) exposure in a mouse model. In this study, we investigated cerebellar-recruited behaviors in adult female mice that were exposed to EtOH from postnatal day (P) 4 to P9. We investigated whether changes in oligodendrocyte lineage markers were present in adulthood. Methods: C57BL/6J offspring received a total of 5.0 g/kg/day of either ethanol (EtOH) or saline in two separate doses delivered subcutaneously two hours apart from P4 to P9. On P21, offspring were weaned and housed with same-sex littermates throughout the duration of the study. From P60 to P90, females underwent behavioral testing including an open field test (OFT), rotarod, and balance beam. Behavior naïve littermates were euthanized on P105, and cerebella were collected for qPCR to assess oligodendrocyte lineage transcripts. Results: We reported that, following EtOH exposure from P4 to P9, adult female mice had increased ambulatory behaviors in the OFT and subtle changes in behavior in the rotarod and balance beam compared to saline-exposed controls. Despite the behavioral changes observed in adulthood, we found that alterations in oligodendrocyte lineage transcripts present on P10 did not persist into adulthood. Conclusions: Subcutaneous injection of EtOH from P4 to P9 resulted in long-term consequences in locomotor and cerebellar-recruited behaviors in female mice. Full article

An excessive activation of the tryptophan–kynurenine (TRP-KYN) pathway, frequently observed in metabolic and inflammatory disorders, leads to disturbances in the balance between neurotoxic and neuroprotective metabolites. These alterations may contribute to neuronal dysfunction and cognitive impairment, highlighting the importance of modulating this pathway in the context of neuroprotection. Metformin, apart from the AMPK activation and its broad anti-inflammatory actions, has been indicated as a drug capable of influencing the synthesis of TRP metabolites, including the neuroprotective kynurenic acid (KYNA), whereas the effects of sitagliptin in this regard are not known. Here, the effects of sub-chronic metformin or sitagliptin treatment on the brain levels of kynurenines and on functional alterations within the TRP-KYN pathway were evaluated in vivo, in adult non-diabetic Wistar male rats. A 5-day treatment with metformin decreased cortical TRP and KYNA, hippocampal KYN, and cerebellar levels of all studied kynurenines, whereas in the striatum, KYNA level increased. In contrast, sitagliptin did not alter the formation of kynurenines in the examined structures. However, both of the tested drugs had a significant impact on TRP/L-KYN or L-KYN/KYNA ratios in different parts of the brain. These findings indicate a prominent region-specific effect of metformin on brain kynurenines. In conclusion, commonly used antidiabetic agents differ in their impact on central TRP metabolism, which may have significant implications for understanding their potential neuroprotective effects and role in cognitive impairment. Full article

Cognitive impairment (CI) is a common and disabling manifestation of multiple sclerosis (MS), yet it remains underdiagnosed in clinical settings. This study aims to identify the volumetric MRI markers of CI in MS patients. A total of 79 MS patients were enrolled; after exclusions, 63 with relapsing-remitting MS (RRMS) and 7 with primary progressive MS were analyzed. All participants underwent neuropsychological testing (CVLT, BVRT, CTT, VFT, VST, and SDMT). Brain volumes were analyzed using FreeSurfer. In RRMS, 59% had CI (35% single-domain, 24% multidomain). Multidomain CI was linked to reduced left cerebellar white matter and bilateral pallidum volumes, slight choroid plexus enlargement, and higher lesion volume versus cognitively preserved patients. Significant correlations were found between brain volumes and cognitive test scores: cerebellar and cerebral white matter, corpus callosum, subcortical gray matter, and thalamus volumes correlated positively with measures of processing speed, memory, and verbal fluency, while higher lesion load and larger choroid plexus volumes were associated with poorer cognitive performance. CI in MS is linked to both global and regional brain atrophy, as well as lesion load. Volumetric MRI, including choroid plexus analysis, may represent candidate imaging correlates of CI; however, longitudinal and externally validated studies are needed to confirm their predictive value and clinical utility. Full article

Objectives: To evaluate regional anatomical differences in brain volume, surface area, and cortical thickness between children with breath-holding spells (BHSs) and a control group using morphometric MRI analyses. Methods: Three-dimensional T1-weighted cranial MRI data from 48 children with BHSs and 50 control children were retrospectively analyzed, yielding volumetric, surface area, and cortical thickness measures for 135 brain regions. All measurements were assessed relative to total intracranial volume (ICV). Group comparisons were performed using analysis of covariance with age, sex, and ICV as covariates, followed by Benjamini–Hochberg false discovery rate correction (q < 0.05). Results: The BHS group exhibited reduced bilateral amygdala volumes (left: q = 0.042; right: q = 0.038). Both cortical thickness and volume were reduced in the right anterior insula (thickness: q = 0.046; volume: q = 0.049). In addition, cortical thickness was reduced in the bilateral anterior cingulate cortices (left: p = 0.019, q = 0.045; right: p = 0.017, q = 0.043) as well as in the right medial frontal cortex (p = 0.009, q = 0.036). Subregional cerebellar analysis demonstrated volume reductions in the right lobule VI (q = 0.031), left lobule VIIA (Crus I) (q = 0.043), and vermis IX–X (q = 0.039). Conclusions: Detecting measurable morphometric changes in brain regions involved in autonomic and emotional regulation in children with BHSs will contribute to understanding the neurobiological characteristics associated with BHSs. Full article

Background/Objectives: Neurodegenerative cerebellar ataxia (CA) is a movement disorder caused by progressive cell death in the cerebellum. Motor imagery represents a potential therapeutic tool to improve motor function by “exercising” brain regions associated with movement, without the need for overt activity. This study assessed the feasibility of combining motor imagery with real-time functional magnetic resonance imaging neurofeedback (rt-fMRI-NF) to improve motor function in CA. Methods: During finger tapping conditions, 16 participants with CA pushed a button at the same frequency in time with cross flashing at 1 Hz or 4 Hz, and this information was used to train the model. During motor imagery, participants imagined finger tapping while undergoing rt-fMRI-NF with visual feedback, steering them toward activating their motor circuit. Afterwards, they completed finger tapping again. FMRI analysis compared successful motor imagery trials versus all other imagery events. Brain activity on successful trials was covaried with pre–post rt-fMRI-NF tapping improvement scores. Results: Tapping was more accurate at 1 Hz than 4 Hz, and larger tapping error rates correlated with greater movement impairments. While not significant at the group level, 9 of the 16 participants improved tapping accuracy following rt-fMRI-NF. The size of motor improvements correlated with successful motor imagery activity at 1 Hz in the frontal lobe, insula, parietal lobe, basal ganglia, and cerebellum. Motor improvements were not associated with neurological impairment severity, mood, cognition, or imagery vividness. Conclusions: Feasibility was demonstrated for motor imagery therapy with neurofeedback to potentially improve fine motor precision in people with CA. Brain regions relevant to this process may be considered for targets of non-invasive therapeutic interventions. Full article

Background: During the first 2 years of life, human white matter (WM) undergoes rapid development, establishing a structural foundation for later neurodevelopment. Methods: We conducted a mixed-model analysis for repeated measures to investigate the developmental trajectories of functionally distinct 26 WM pathways between preterm and full-term groups during the first 2 years of life using diffusion tensor imaging (total scans = 174; preterm = 58; full-term = 23). Results: We observed significant differences between the preterm and full-term groups in the developmental trajectories associated with motor function (left corticospinal tract and left pre-primary motor cortex connection tracts), visual processing (bilateral pathway between the V1/V2 and V4, PV-MT, pathway connecting the V1/V2 and V5/MT, and optic radiation), and cognition (genu, body, and splenium of the corpus callosum). Furthermore, inter-regional correlation matrix analysis revealed stronger connectivity, specifically within motor- and visual-related pathways, in the preterm group than that for the full-term group, suggesting an adaptive mechanism that supports circuit-level resilience following preterm birth. Moreover, in the model investigating the associations between the WM individual rate of change and long-term neurodevelopmental outcomes, the middle cerebellar peduncle (MCP) tract showed the strongest associations with motor scores, suggesting that faster maturation of the MCP tract may enhance motor functions as a key compensatory mechanism following preterm birth. Conclusions: Delineating the longitudinal change rates of specific WM pathways not only deepens our understanding of the neurodevelopmental sequelae of prematurity but also highlights their potential as early biomarkers to guide timely interventions. Full article