Search Results (330)

Introduction: The fetal ganglionic eminence (GE) is a transient brain structure involved in interneuron development; its abnormalities may be associated with malformations of cortical development (MCD). This systematic review evaluated the feasibility and clinical value of transvaginal neurosonography for fetal GE assessment. Material and Methods: PubMed, Scopus, and Web of Science were searched from January 2015 to June 2026. Human in vivo ultrasound studies of the fetal GE were included. Results: Thirteen studies comprising 890 fetuses were included. GE visualization ranged from 71% to 100%, with highest rates using dedicated three-dimensional transvaginal neurosonography at 9–22 weeks. Measurement reproducibility was good to excellent. GE cavitation and enlargement were associated with MCD in selected high-risk cohorts, but reported frequencies varied substantially. Conclusions: Transvaginal neurosonography permits feasible and reproducible visualization of the fetal GE in experienced hands. Small studies, heterogeneous protocols, and limited long-term outcome data preclude routine GE assessment at present. Full article

Background: Transvenous embolisation (TVE) has emerged as a promising treatment option for selected brain arteriovenous malformations (bAVMs). Objective: To evaluate the safety and efficacy of TVE-based treatment strategies for bAVMs. Methods: This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020-compliant systematic review and meta-analysis was registered in PROSPERO (CRD420261397818). PubMed, Embase, Cochrane CENTRAL, and Scopus were searched on 20 May 2026, supplemented by citation screening. Studies reporting TVE for bAVMs in ≥5 patients were included. Binary outcomes were pooled using random-effects binomial-normal generalised linear mixed models (GLMMs) with a logit link under an intention-to-treat framework. Results: Twelve studies comprising 239 patients were included; 57.7% underwent combined transarterial/transvenous embolisation. Complete angiographic occlusion was 92.2% (217/239; 95% CI, 84.5–96.2%; I² = 0%) overall and 97.1% (149/160; 95% CI, 76.6–99.7%; I² = 0%) among patients with ≥3 months of imaging follow-up. Functional independence (mRS 0–2) was 85.0% (155/180; 95% CI, 68.7–93.7%; I² = 55%), and technical success was 97.1% (219/227; 95% CI, 91.5–99.0%; I² = 0%). GLMM pooled rates were 0.7% for ischaemic complications, 12.3% for haemorrhagic complications, 3.3% for permanent neurological morbidity, 2.3% for overall mortality, 0.8% for procedure-related mortality, and 13.9% for any procedure-related complication or death. Conclusions: TVE-based strategies are associated with high angiographic occlusion and favourable functional outcomes in carefully selected bAVMs, but the evidence is predominantly observational and safety estimates remain uncertain. As most patients underwent combined transarterial/transvenous treatment, these findings should not be interpreted as estimates of standalone TVE. Full article

Brain arteriovenous malformations (AVMs) are complex cerebrovascular lesions characterized by abnormal direct connections between arteries and veins, resulting in altered hemodynamics and an increased risk of rupture. Following PRISMA, a comprehensive review on CFD-based modelling in brain AVMs was conducted across major scientific databases, including Pub-Med/MEDLINE, Scopus, Web of Science, Google Scholar, EBSCO Academic Search and IEEE Xplore, evaluating its role in hemodynamic analysis and pre-procedural planning. Twenty-three studies met the inclusion criteria and were analyzed through both qualitative synthesis and bibliometric approaches. Bibliometric analysis revealed a growing research interest in image-based modelling, 4D flow imaging and virtual embolization after 2021. Despite recent advances in study of hemodynamics simulations, the application of computational fluid dynamics (CFD) to brain AVMs remains challenging due to their complex vascular architecture and highly heterogeneous flow patterns. Nevertheless, CFD remains an important imaging modality for characterizing the lesion and guiding pre-interventional decision making. Full article

Microtubules are essential cytoskeletal components comprising alpha- and beta-tubulin proteins that facilitate organelle positioning, cell migration, division, and intracellular trafficking. Mutations in tubulin genes can lead to tubulinopathies, a class of rare genetic neurodevelopmental disorders characterized by a range of brain malformations and other clinical features. Recent studies have shown that pathogenic variants in beta-tubulin genes such as TUBB^G308S have been found to underlie the development of ciliopathies, disorders impacting cilia, important organelles for development and cell motility. Thus, mutations in distinct tubulin genes, which present a significant hurdle for the development of therapeutic gene editing strategies and targeted therapeutics. Here, we describe the development of a mutation-independent treatment strategy based on the upregulation of non-mutated beta-tubulin isotype protein using CRISPR-Cas9 activation. By increasing the expression of various beta-tubulin proteins, we demonstrate a restoration of the microtubule network and primary cilia formation. Full article

Background/Objectives: Brain arteriovenous malformations (bAVMs) are complex cerebrovascular lesions that carry a substantial risk of intracranial hemorrhage, yet the biological mechanisms underlying vascular remodeling remain incompletely understood. As increasing evidence suggests that inflammatory processes contribute to vascular remodeling and bAVM progression, this study aimed to characterize the cellular composition of the immune microenvironment in human bAVMs at single-cell resolution and to identify immune cell populations associated with transcriptional programs related to angiogenesis and extracellular matrix remodeling. Methods: Publicly accessible single-cell RNA sequencing data from five human bAVM samples and five control brain specimens were analyzed. After quality control and data integration, immune cell types were annotated based on canonical marker gene expression. To assess biological processes relevant to vascular remodeling, the expression of predefined gene sets associated with angiogenesis and extracellular matrix remodeling, derived from the Molecular Signatures Database (MSigDB), was quantified across cell populations using rank-based gene set scoring (UCell). Differences between bAVM and control samples were evaluated at the sample level using the Wilcoxon rank-sum test. For each immune cell type, mean UCell scores were calculated per biological sample and compared between groups. To account for multiple comparisons across cell types, p-values were adjusted using the Benjamini–Hochberg procedure. Results: After quality control, 46,360 immune cells were analyzed. Compared with control tissue, bAVMs showed numerically higher proportions of lymphoid (activated T cells and CD8 T cells) and myeloid populations (M1-like macrophages, monocytes, and dendritic cells). Angiogenesis-related transcriptional activity was highest in myeloid cells and significantly increased in bAVMs, particularly in M1-like macrophages (UCell score 0.22 vs. 0.13), dendritic cells (0.16 vs. 0.10) and monocytes (0.20 vs. 0.15), whereas proliferating CD8 T cells showed a lower score (0.04 vs. 0.05; adjusted p = 0.040 for all four). Extracellular matrix-related programs showed a similar but weaker and non-significant pattern in myeloid populations (e.g., monocytes, dendritic cells, microglia-like cells; adjusted p = 0.09). Conclusions: Our findings identify myeloid cells, particularly M1-like macrophages, monocytes and dendritic cells, as important immune populations associated with angiogenesis in bAVMs. These findings highlight a potential role of immune-driven vascular remodeling in the pathophysiology of bAVMs. Full article

Background: Pathogenic variants in the PPP1R12A gene have been associated with a malformation syndrome involving the brain and the genitourinary systems (GUBS, MIM #618820). To date, neither hearing loss (HL) nor inner ear malformations have been reported in affected individuals, and these features are therefore not currently regarded as part of the PPP1R12A-related phenotype. Moreover, functional evidence supporting the pathogenicity of several reported variants remains limited. Methods: We investigated a 12.5-year-old patient presenting with profound bilateral sensorineural hearing loss associated with inner ear malformations, genitourinary and central nervous system abnormalities. The patient underwent comprehensive clinical, audiological and radiological assessments, followed by genetic testing via trio-based whole-exome sequencing (WES). The molecular consequences of the identified variant were evaluated through minigene splicing assay and RT–PCR analysis on RNA extracted from peripheral blood cells. Results: WES identified a novel heterozygous splicing variant (c.792+3A>C) in the PPP1R12A gene (NM_002480.3). Functional studies demonstrated that this variant causes complete skipping of exon 5, resulting in a frameshift and the introduction of a premature termination codon. RT–PCR analysis confirmed the presence of the alternatively spliced transcript lacking exon 5. In addition, an extensive review of the literature indicated that no clear genotype–phenotype correlation has yet been established for PPP1R12A-related disorders and, whereas the majority of previously reported patients share brain and genitourinary malformations our patient additionally presented with profound bilateral sensorineural HL and inner ear malformations. Conclusions: Our findings suggest that PPP1R12A-related disorders may exhibit a broader phenotypic variability than previously recognized and we further propose that HL and inner ear malformations may represent novel features associated with this clinical spectrum. Moreover, our study underscores the importance of functional studies for accurately defining the molecular consequences of novel variants and establishing appropriate clinical correlations. Full article

Background & Objectives: Endovascular embolization has matured into a sophisticated, precision-guided discipline that is central to the management of complex neurovascular pathologies. This review synthesizes contemporary treatment strategies, evaluating the advanced material characteristics of conventional inert liquid polymers, specifically non-adhesive ethylene vinyl alcohol (EVOH) copolymers and adhesive cyanoacrylates, alongside their targeted clinical applications in brain arteriovenous malformations (bAVMs), dural arteriovenous fistulas (dAVFs), hypervascular intracranial tumors, and chronic subdural hematomas (CSDHs). Furthermore, it examines the critical material and hemodynamic constraints that limit these agents in cerebral aneurysm repair. Methods: A comprehensive literature synthesis through 3 July 2026 was integrated with peer-reviewed clinical illustrations to evaluate both procedural mechanics and the necessity of post-procedural physiological management. Review Findings: Embolization serves a critical dual role: as a definitive curative therapy and as an essential preoperative or radiosurgical adjunct. As demonstrated by recent clinical validations, technical angiographic success must be closely coupled with vigilant neurocritical oversight to manage profound, localized hemodynamic shifts. While these conventional methods represent established clinical practice, the field is evolving away from inert mechanical occlusion toward a highly integrated approach. The convergence of stimuli-responsive “smart” hydrogels and endovascular robotics is being evaluated for potential roles in transforming these interventions into dynamic, bioactive platforms capable of modulating disease-specific mechanisms, such as Rat Sarcoma-Mitogen-Activated Protein Kinase (RAS-MAPK) and Bone Morphogenetic Protein (BMP) signaling in bAVMs or the Von Hippel-Lindau/Vascular Endothelial Growth Factor (VHL/VEGF) axis in hypervascular tumors. This review further analyzes landmark data, including the Squid Trial For the Embolization of the Middle Meningeal Artery for Treatment of Chronic Subdural Hematoma (STEM) trial for CSDH, providing a synthesis for translating these advanced material sciences into standardized, multidisciplinary neurointerventional care. Full article

Background and Objectives: Posterior fossa anomalies (PFAs) represent a heterogeneous group of congenital malformations involving the cerebellum and adjacent structures. Prenatal counseling remains challenging because neurodevelopmental outcomes vary substantially according to the specific anomaly. This study aimed to evaluate ultrasonographic and fetal magnetic resonance imaging (MRI) characteristics, associated anomalies, genetic test results, and perinatal and neurodevelopmental outcomes of prenatally diagnosed PFAs in a tertiary care population. Materials and Methods: This retrospective study included 115 fetuses diagnosed with PFAs between 2020 and 2024. PFAs were categorized into “simple” (mega cisterna magna, Blake’s pouch cyst [BPC], and arachnoid cyst) and “complex” (Dandy–Walker malformation [DWM], vermian agenesis/hypoplasia, cerebellar hypoplasia, Joubert syndrome, Walker–Warburg syndrome, and pontocerebellar hypoplasia). Maternal characteristics, associated cerebral and extracerebral anomalies, fetal MRI findings, genetic test results, and pregnancy and postnatal outcomes were analyzed. Results: Among 115 cases, 44.3% were isolated, and 55.6% were non-isolated. Ventriculomegaly was detected in 35.6% of cases and was significantly more frequent in the complex group (47.9% vs. 14.2%). Fetal MRI was performed in 35.6% (n = 41) of cases and demonstrated a 24.3% discrepancy rate with ultrasound, mainly in differentiating DWM from BPC. Genetic testing was performed in 66.9% of cases, revealing chromosomal abnormalities in 15.6% of the total cohort. Complex anomalies, including cerebellar hypoplasia and vermian agenesis/hypoplasia, were more frequently associated with pathogenic copy-number variants and monogenic disorders. The simple group (n = 42) had favorable outcomes, with an 89.2% survival rate and neurodevelopmental delay in 15.2% of survivors. In contrast, the complex group (n = 73) had significantly poorer outcomes (p < 0.001), with a 38.1% survival rate, 42.5% rate of pregnancy termination, and neurodevelopmental delay in 56.3% of survivors. Conclusions: This study highlights the persistent diagnostic challenges associated with PFAs and underscores the importance of multimodal imaging and comprehensive genetic evaluation. The proposed simple–complex classification provides a clinically meaningful framework for prognostication and parental counseling. Future research should prioritize prospective multicenter studies with higher rates of comprehensive genetic testing coupled with standardized long-term neurodevelopmental follow-up to refine the understanding of the natural history and prognostic trajectory of these complex brain malformations. Full article

Background/Objectives: Surgical management of cerebral cavernous malformations (CCMs) within eloquent brain regions presents a high risk of neurological deficits. This study describes the clinical outcomes and technical feasibility of microsurgical resection for symptomatic eloquent CCMs, detailing the integration of advanced intraoperative adjuncts aimed at optimization of seizure control and functional preservation. Methods: We conducted a retrospective multicenter analysis of nine adult patients who underwent microsurgical resection for symptomatic eloquent CCMs between January 2021 and December 2025 across two tertiary centers in Slovenia. Intraoperative modalities included 100% neuronavigation, 55.6% intraoperative ultrasound, 77.8% intraoperative neuromonitoring (IONM) with motor and somatosensory evoked potentials, and 22.2% awake craniotomies. Results: Seizures were the primary clinical presentation in 77.8% of patients (66.7% medically refractory), and the overall hemorrhage rate was 66.7%. Gross total resection of the CCM was achieved in 100% of cases, with complete hemosiderin rim removal in 80% of applicable lesions. Early postoperative complications occurred in four patients, but at the maximum 48-month follow-up, 100% of the cohort achieved complete seizure control, and 44.4% successfully discontinued antiepileptic drugs. Long-term focal neurological deficits persisted in only two patients, while 77.8% were able to work following surgery. Conclusions: Microsurgical resection remains a well-established treatment modality for symptomatic CCMs. In this small, descriptive series of patients with lesions in functionally critical regions, high rates of gross total resection and favorable long-term seizure freedom were observed. These findings suggest that a multimodal approach combining anatomical neuronavigation with functional IONM may help minimize permanent morbidity, though larger cohorts are required to establish definitive efficacy. Full article

Background and Importance: Congenital encephalocele refers to the protrusion of CNS tissue through a skull defect. As a rare neural tube malformation, clinical evidence is particularly limited for large encephaloceles, and management is subject to ongoing discussions. Clinical Presentation: A 3-month-old boy presented with a left hemisphere herniation above the level of the Sylvian fissure into a congenital parietal encephalocele. No focal deficits were appreciated. We hypothesized that early prenatal damage due to protruding brain tissue may have resulted in unihemispheric motor control of both body sides. As such, surgical repair guided by intraoperative electrophysiology and plastic reconstruction was scheduled. Intraoperatively, bilateral and symmetric extremity response upon transcranial electric stimulation of the contra-lesional right hemisphere was detected, whereas no responses from direct cortical and subcortical stimulation of the herniated brain parenchyma were elicited. Complete resection of the herniated supra-insular hemisphere was provided, and no ischemic changes or new deficits occurred. At 24-month follow-up, the patient showed voluntary movements with both upper extremities and voluntary grasping with his left (non-paretic) hand, no mirror movements, no signs of spasticity, good eye contact, and could speak several words. Conclusions: Safe resection with excellent outcome can be provided even for large encephaloceles. Intraoperative electrophysiological findings aid in identifying the absence of cortico-spinal projections and appear helpful to avoid post-operative deficits. Full article

Background/Objectives: Absent septum pellucidum (ASP) is a rare fetal midline brain finding that may occur in isolation or alongside broader central nervous system (CNS) malformations, genetic disorders, or septo-optic dysplasia (SOD). Accurate prenatal diagnosis and counseling remain challenging because apparently isolated ASP may be reclassified following fetal magnetic resonance imaging (MRI), postnatal neuroimaging, or specialist assessment. This structured narrative review aimed to synthesize current evidence on prenatal imaging findings, associated anomalies, genetic evaluation, and postnatal outcomes in fetuses with ASP. Methods: This structured narrative review used PRISMA-informed reporting. PubMed and Google Scholar were searched for full-text English-language studies published from 2014 through the updated search date (8 June 2026). Data on gestational age at diagnosis, imaging classification, associated anomalies, genetic testing, postnatal assessment, and neurodevelopmental, ophthalmological, and endocrine outcomes were extracted. Study methodological quality was appraised using Joanna Briggs Institute tools. Results: Seven studies comprising 342 fetal ASP cases were included. Of these, 94 cases (27.5%) were classified as isolated ASP prenatally, but only 57 remained isolated postnatally when follow-up data were available. SOD was confirmed after birth in 11 of 94 (11.7%) fetuses with prenatally isolated ASP. As definitions, imaging protocols, genetic testing strategies, and follow-up duration differed substantially across studies, these pooled values are descriptive observations rather than formal quantitative estimates. Conclusions: ASP is a heterogeneous prenatal finding. The prognosis is most favorable when ASP remains isolated following a detailed prenatal and postnatal evaluation. Multidisciplinary follow-up involving fetal medicine, neuroradiology, genetics, ophthalmology, endocrinology, and neurology is essential for risk stratification and counseling. Full article

Background/Objectives: Hip arthroscopy is a minimally invasive procedure with rare complications that can occur due to air entry outside the joint space. Case Presentation: A 19-year-old patient underwent right hip arthroscopy with attempted joint venting. The next morning, she had pain in her right leg, neck, and chest with paresthesias over her hands and feet. A subsequent emergency department physical exam revealed crepitation of the lower extremities, abdomen, chest, and neck caused by air entrance during arthroscopy. The patient also reported blurred near vision. Additionally, the pupils were fixed, did not accommodate, and were dilated at 7 mm. Computed tomography scans revealed subcutaneous emphysema, pneumoperitoneum, pneumomediastinum, and cervicofacial emphysema. Magnetic resonance imaging of the brain revealed a Chiari I malformation. The patient received four hyperbaric oxygen treatments. By the fourth treatment, near visual acuity had improved, but far visual acuity had worsened. Vision had returned to normal eight days after discharge. Conclusions: It is proposed that the patient’s reduced near vision, accommodation paralysis, and fixed and dilated pupils were brought about by pneumomediastinum and cervicofacial emphysema, inhibiting the ability of the pupils to constrict, causing bilateral mydriasis and accommodation paralysis for near targets. Additionally, the subsequent transient myopic shift is a known complication of hyperbaric oxygen therapy, which increases the refractive index of the crystalline lens. Full article

Capillary malformation–arteriovenous malformation syndrome is a rare spectrum of vascular anomalies characterized by capillary malformations and high-flow vascular malformations, caused by loss-of-function mutations in the RASA1 and/or EPHB4 genes. These mutations disrupt vascular differentiation and lead to complex malformations involving the brain, skin, and systemic vasculature. Since the first description in 2003, more than 200 cases have been reported, but intracranial arteriovenous shunts during the neonatal period remain extremely rare, as well as reports of the dual mutation RASA1 + EPHB4 or the immunological impact of the EPHB4 mutation. We report three cases of neonates presenting with early-onset high-flow shunts, each exhibiting a distinct genetic signature: CM-AVM1 (RASA1 mutation), CM-AVM2 (EPHB4 mutation), and dual variant (combined EPHB4 and RASA1 mutations). We analyzed and compared the clinical evolution, Doppler ultrasound trends, EEG, MRI and genetic data to highlight the distinct genotype–phenotype spectrum. Early multimodal hemodynamic evaluation of neonates with CM-AVM allows the identification and optimum management of life-threatening shunts at the earliest possible stage. Full article

Background/Objectives: Minor physical anomalies (MPAs) are subtle morphological markers of disrupted neuroectodermal development occurring during early gestation. Their increased prevalence has been reported in several neurodevelopmental and psychiatric conditions, including schizophrenia. However, data on MPAs in pediatric psychosis remain limited. This exploratory descriptive study aimed to characterize the occurrence of MPAs and congenital malformations in children presenting with early-onset psychotic symptoms and to illustrate the clinical heterogeneity through two representative cases. Methods: All participants underwent a comprehensive head-to-toe examination by a trained child and adolescent psychiatrist to identify MPAs. Key anatomical regions, including the face, hair vortex, palate, and extremities, were systematically photographed. Results were corroborated by MRI brain screening and consulted with a clinical geneticist. Anomalies were classified using the standardized Elements of Morphology terminology. Results: Among the 19 study participants, seven (37%) were diagnosed with very early-onset schizophrenia (VEOS). Identified minor physical anomalies included epicanthus (n = 5), café au lait spots (n = 2), and discoloured spots (n = 1). Furthermore, major congenital malformations were detected, specifically Arnold–Chiari malformation type I (n = 1), incomplete hippocampal inversion (n = 1), and a temporal cortex malformation (n = 1). Conclusions: MPAs and selected neuroanatomical anomalies were observed in a subset of children with early-onset psychotic symptoms. While the small sample size and absence of a control group limit interpretability, these exploratory findings suggest that systematic physical examination may provide supportive clinical information in the assessment of pediatric psychosis. Larger, controlled studies are needed to clarify whether specific MPAs may serve as early markers of neurodevelopmental vulnerability. Full article

Zika virus (ZIKV) infection during pregnancy is a critical driver of Congenital Zika Syndrome (CZS), yet the mechanisms of pathogenesis at the placental barrier remain incompletely understood. This article is a translational, observational, and experimental study combining clinical placental analyses, placental explants cultures and in vivo murine model to investigate the mechanisms involved in ZIKV infection. We evaluate the histopathological analyses to verify presence of inflammation in ZIKV-infected human placentas from newborns with CZS and without CZS (N-CZS), identifying more intense Hofbauer cell hyperplasia, villitis and decidual inflammation in CZS group. Moreover, placental immunohistochemistry analyses identified decreased TLR4 expression in the villi and reduced TNF and IL-10 levels across placental layers of CZS group. Next, we investigated the effects of inflammation on viral replication and explored whether the flavonoid Naringenin (NGN) could modulate this inflammation. Using a placental villous explant model, we verified that inflammation induced by LPS exacerbates viral replication and pathological markers. Notably, treatment with the NGN rescued the inflammatory and virological outcomes. These findings were further validated in a murine model of congenital infection, where NGN administration alleviated microcephaly-related structural alterations in ZIKV-exposed neonates. Our results indicate that placental inflammation is a key provocateur of ZIKV replication and subsequent fetal brain malformation. Furthermore, we identify NGN as a promising bifunctional antiviral and anti-inflammatory candidate for mitigating the developmental impacts of ZIKV infection. Full article