Search Results (119)

Background/Objectives: Alterations in immunoinflammatory activation may constitute a pathogenetic mechanism in neurodevelopmental disorders (NDDs). Blood cell count (CBC) parameters and hematological inflammatory indices (neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio) are now assuming a greater role as potential biomarkers for NDDs. Methods: In this retrospective observational study, we gathered data on 135 medication-free individuals aged 6 to 17 years: 90 with NDDs (34 with autism spectrum disorder (ASD), 29 with attention-deficit/hyperactivity disorder, 14 with intellectual disability, and 13 with tic disorder) and 45 typically developed controls. The variables analyzed were compared using analysis of variance including Bonferroni posthoc testing for pairwise comparisons Significance was defined as p < 0.05. Results: The analysis of variance revealed statistical significance for all evaluated CBC parameters, as well as for the lymphocyte-to-monocyte ratio. Notably, subjects with ASD exhibited increased values of neutrophils, lymphocytes, monocytes, and eosinophils compared to both typically developing subjects and other NDDs. The lymphocyte-to-monocyte ratio was found to be lower in the tic disorder group compared to typically developing subjects. The elevated lymphocyte and monocyte levels in ASD subjects might reflect chronic low-grade inflammation. Conclusions: Consistent with the evidence in literature, statistically significant differences between the NDD group and typically developed subjects in the CBC parameters were found. The principal limitations of this investigation are the restricted sample size and the exclusion of specific NDD subtypes. Future research is needed to evaluate CBC parameters and inflammatory indices in a broader spectrum of NDDs to better understand the immunoinflammatory response specific to each disorder. Full article

Neurodevelopmental disorders (NDDs), including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID), and tic disorders, comprise a range of conditions that originate in early childhood and impact cognitive, behavioral, and social functioning. Despite their clinical heterogeneity, they often share common molecular and neurobiological framework. This narrative review aims to examine the role of neurotrophins—particularly the brain-derived neurotrophic factor, nerve growth factor, and related molecules—in the pathophysiology of NDDs, and to explore their potential as biomarkers and therapeutic targets. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, including both clinical and preclinical studies. Neurotrophins are critically involved in brain development, influencing neurogenesis, synaptic plasticity, and neuronal survival. Dysregulation in their signaling pathways has been associated with core features of ASD and ADHD and may modulate cognitive outcomes in ID. Emerging evidence also supports a role for neuroimmune interactions and neurotrophic dysfunction in tic disorders. However, findings across studies remain inconsistent due to methodological variability and limited longitudinal data. Future research should aim for standardized methodologies and stratified, longitudinal designs to clarify their role across developmental stages and clinical phenotypes. Full article

One of the major challenges in diagnosing various diseases, including neurological and neurodegenerative disorders, as well as carcinogenesis, is detecting unlabeled neurotransmitters. Surface-enhanced Raman spectroscopy (SERS) and surface-enhanced infrared spectroscopy (SEIRA) are promising methods for neurotransmitter biosensing and bioimaging. These methods are unique in that they are non-destructive and can identify molecular fingerprints. In this study, these methods were used to detect the following potent bradykinin (BK) antagonists: [D-Arg⁰,Hyp³,Thi⁵,D-Tic⁷,Oic⁸]BK, [D-Arg⁰,Hyp³,Thi⁵,D-Phe⁷,Thi⁸]BK, [D-Arg⁰,Hyp³,Igl⁵,D-Phe(5F)⁷,Oic⁸]BK, and [D-Arg⁰,Hyp³,Igl⁵,D-Igl⁷,Oic⁸]BK. The peptides were immobilized on a sensor surface consisting of silver (AgNPs) and gold (AuNPs) nanoparticles. These sensors have uniform particle sizes and small size distributions. Thanks to fast synthesis, easy handling, and reproducible results, these sensors enable routine testing. The vibrational structure of these peptides could not be determined using classical vibrational methods (Raman and IR) or surface-enhanced methods (SERS and SEIRA). This work presents the results of that research. Additionally, the SEIRA spectrum for BK or its analogs has not yet been published. This study presents research using SERS and SEIRA that shows that AgNP and AuNP sensors can detect the peptides under investigation. SERS is a more selective method than SEIRA because it allows for the differentiation of peptides based on the enhancement of certain bands in the SERS spectra. Furthermore, each peptide uniquely interacts with AuNPs, whereas all peptides bind to AgNPs via the C-terminus in different orientations. Consequently, the AuNP sensor is more selective than the AgNP sensor. Some bands were selected as markers for the sensing of specific peptides. Full article

Background/Objectives: The objective of this study was to validate a new parent-reported scale for tracking Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). PANS is a condition characterized by a sudden and severe onset of neuropsychiatric symptoms. To meet diagnostic criteria, an individual must present with either obsessive–compulsive disorder (OCD) or severely restricted food intake, accompanied by at least two additional cognitive, behavioral, or emotional symptoms. These may include anxiety, emotional instability, depression, irritability, aggression, oppositional behaviors, developmental or behavioral regression, a decline in academic skills such as handwriting or math, sensory abnormalities, frequent urination, and enuresis. The onset of symptoms is usually triggered by an infection or an abnormal immune/inflammatory response. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a subtype of PANS specifically linked to strep infections. Methods: We developed a 101-item PANS/PANDAS and Related Inflammatory Brain Disorders Treatment Evaluation Checklist (PTEC) designed to assess changes to a patient’s symptoms over time along 10 subscales: Behavior/Mood, OCD, Anxiety, Food intake, Tics, Cognitive/Developmental, Sensory, Other, Sleep, and Health. The psychometric quality of PTEC was tested with 225 participants. Results: The internal reliability of the PTEC was excellent (Cronbach’s alpha = 0.96). PTEC exhibited adequate test–retest reliability (r = 0.6) and excellent construct validity, supported by a strong correlation with the Health subscale of the Autism Treatment Evaluation Checklist (r = 0.8). Conclusions: We hope that PTEC will assist parents and clinicians in the monitoring and treatment of PANS. The PTEC questionnaire is freely available at neuroimmune.org/PTEC. Full article

Background/Objectives: A direct link between sensory processing disorder (SPD) and strabismus has not been systematically investigated, though prior studies suggest sensory modulation may influence visual behaviors. Traditional approaches view strabismus through a binary lens—either normal or pathological motor deviation. This report presents a proof-of-concept case suggesting strabismus may represent a neurobehavioral manifestation of sensory processing imbalance, rooted within the broader framework of SPD. Methods: We report a pediatric case marked by episodic monocular eye closure triggered by environmental stimuli, without identifiable ophthalmologic or neurologic pathology. The child’s symptoms were most consistent with sensory over-responsivity (SOR), a subtype of SPD, manifesting as stimulus-bound monocular eye closure and secondary self-regulatory behaviors. Results: We propose the Fusion Dysregulation Hypothesis, suggesting that exotropia and esotropia represent opposing outcomes along a continuum of sensory connectivity: exotropia arising from neural underwiring (hyporesponsivity and fusion instability), and esotropia from overwiring (hyperresponsivity and excessive fusion drive). Our case, marked by sensory hyperresponsivity, showed frequent monocular eye closure that briefly disrupted but did not impair fusion. This suggests an “overwired” binocular system maintaining single vision despite sensory triggers. In early-onset esotropia, such overconnectivity may become maladaptive, leading to sustained convergence. Conversely, autism spectrum disorder, typically associated with hypoconnectivity, may predispose to exotropia through reduced fusion maintenance. Conclusions: These findings highlight the need for interdisciplinary evaluation. We advocate for structured sensory profiling in children presenting with strabismus and, conversely, for ophthalmologic assessment in those diagnosed with SPD. While our findings remain preliminary, they support a bidirectional screening approach and suggest that sensory modulation may play a previously under-recognized role in the spectrum of pediatric strabismus presentations. Full article

Cannabinoid receptor 1 (CB₁) signalling is critical for weight gain and for milk intake in newborn pups. This is important as in humans, low birth weight increases the risk for attention-deficit hyperactivity disorder (ADHD). Moreover, some children with ADHD also have Tourette syndrome (TS). However, it remains unclear if insufficient CB₁ receptor signalling may promote ADHD/TS-like behaviours. Here, ADHD/TS-like behaviours were studied from postnatal to adulthood by exposing postnatal wild-type CB₁ and Cannabinoid receptor 2 (CB₂) knockout mouse pups to SR141716A (rimonabant), a CB₁ receptor antagonist/inverse agonist. Postnatal disruption of the cannabinoid system by SR141716A induced vocal-like tics and learning deficits in male mice, accompanied by excessive vocalisation, hyperactivity, motor-like tics and/or high-risk behaviour in adults. In CB₁ knockouts, rearing and risky behaviours increased in females. In CB₂ knockouts, vocal-like tics did not develop, and males were hyperactive with learning deficits. Importantly, females were hyperactive but showed no vocal-like tics. The appearance of vocal-like tics depends on disrupted CB₁ receptor signalling and on functional CB₂ receptors after birth. Inhibition of CB₁ receptor signalling together with CB₂ receptor stimulation underlie ADHD/TS-like behaviours in males. This study suggests that the ADHD/TS phenotype may be a single clinical entity resulting from incorrect cannabinoid signalling after birth. Full article

Tourette syndrome (TS) is the most common cause of tics. Tics are classified as motor and phonic tics. The latter (previously also referred to as “vocal tics”) are manifested by simple sounds (simple phonic tics) or complex, often semantically meaningful utterances (complex phonic tics). Methods: We compared the clinical and demographic features of consecutive patients with TS who exhibited simple and complex phonic tics. Results: There were 149 patients, 117 (78.5%) of whom were males; the mean age at evaluation was 19.61 ± 12.97 years. In total, 35 (23.5%) of these manifested complex phonic tics, and 26 (17.4%) had verbalizations. No statistically significant differences were observed between TS patients with simple versus complex phonic tics with respect to sex, age at onset, age at presentation, or comorbid attention-deficit/hyperactivity disorder or obsessive–compulsive disorder. Patients with complex phonic tics more frequently had trunk tics (p = 0.002), complex motor tics (p < 0.001), copropraxia (p = 0.002), a wider variety of phonic tics (p < 0.001) and greater tic severity (p = 0.001). The multivariate regression analysis showed an independent association between trunk tics and complex phonic tics. Conclusions: Complex phonic tics seem to be part of a more widely distributed, severe, and complex presentation of TS, likely representing a continuum within the spectrum of motor and phonic tics. Full article

Trauma remains a leading cause of death and disability in adults, and about 20% of deaths occur due to intractable bleeding. Trauma-induced coagulopathy (TIC) is a complex hemostatic disorder characterized by an abnormal coagulation response, which can manifest as either a hypo-coagulable state, leading to excessive bleeding, or a hypercoagulable state, resulting in thromboembolic events and multiple organ failure. Early diagnosis and correction of hypocoagulability may be lifesaving. Replacement of coagulation factors using blood components as well as counteracting enhanced fibrinolysis with tranexamic acid in association with a strategy of damage control are the current practices in the management of TIC. Nevertheless, the improved comprehension of the several mechanisms involved in the development of TIC might offer space for a tailored treatment with improvement of clinical outcome. This review aims to outline the pathophysiology of TIC and evaluate both established and emerging management strategies. A thorough literature review was made with a specific emphasis on articles discussing the molecular mechanisms of trauma-induced coagulopathy. We utilized PubMed, Scopus, and Web of Science with the main search terms “trauma-induced coagulopathy”, “molecular mechanisms”, and “coagulation pathways”. Full article

The intestine is an important segment of the gastrointestinal tract, which is involved in complex processes that maintain the body’s normal homeostasis. It hosts a vast, diverse, and dynamic microbial community called the gut microbiota, which develops from birth. It has been observed that the gut microbiota is involved in essential physiological processes, including the development of the central nervous system via the gut microbiota–brain axis. An alteration of the gut microbiota can lead to serious health problems, including defective neurodevelopment. Thus, this paper aims to highlight the most recent advances in studies that focus on the link between the gut microbiota and the evolution of neurodevelopmental diseases in children. Currently, studies show that the use of drugs that stimulate and restore the gut microbiota (e.g., probiotics and prebiotics) have the potential to alleviate some of the symptoms associated with conditions such as Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, Tic Disorder, Tourette Syndrome, epilepsy, and Down Syndrome. In addition, due to the challenges associated with drug administration in children, as well as the widespread shortage of medications intended for pediatric use, researchers are working on the development of new delivery systems. Liposome-based systems or solid lipid nanoparticles have been safely used for drug delivery in various pediatric conditions, which may also indicate their potential for use in the administration of microbiota-modulating therapies. Full article

Objectives: Feeding and eating disorders (FED) represent a major public health issue and are the second leading cause of death among psychiatric conditions in children and adolescents. Psychopathological comorbidities play a significant role in the onset and persistence of FED, yet research on their underlying structure remains limited. This study explores the psychiatric comorbidities associated with FED, focusing on common etiopathogenetic factors and their clinical implications. Methods: Data were retrospectively collected from the Italian Regional Center for FED in the Emilia-Romagna Region between June 2023 and April 2024. Diagnoses were assigned following DSM-5 criteria using the Italian version of the semi-structured K-SADS-PL diagnostic interview. Principal component analysis (PCA) was performed to identify latent psychological dimensions underlying FED psychopathology, retaining five components based on the scree plot. Additionally, an analysis of covariance (ANCOVA) was conducted to examine differences in factor scores across FED subtypes, while adjusting for potential confounders. Results: Seventy-two participants were included (mean age: 14.6 years; mean BMI: 18.3 kg/m²; male-to-female ratio: 1:8). Diagnoses were distributed as follows: 63.9% anorexia nervosa (AN), 13.9% other specified feeding and eating disorder (OSFED), 6.9% avoidant restrictive food intake disorder (ARFID), 4.2% binge eating disorder (BED), 4.2% unspecified feeding and eating disorder (UFED), and 2.7% bulimia nervosa (BN). All participants met the criteria for at least one psychiatric comorbidity. Identified psychopathological clusters include the following: (1) mood disorders (66.5%); (2) anxiety disorders (87.5%); (3) obsessive–compulsive and related disorders (47.2%); (4) neurodevelopmental disorders, i.e., attention-deficit/hyperactivity disorder (ADHD) (30.5%); (5) disruptive and impulse-control disorders (13.9%); and (6) psychotic symptoms (40.3%). No instances of tic or elimination disorders were detected. Conduct disorder was more prevalent among UFED, BED, and BN patients compared to other FED (p = 0.005), and moderate/severe ADHD was associated with higher body mass index (BMI) (p = 0.035). PCA revealed distinct psychological dimensions underlying FED, while ANCOVA indicated significant differences in factor scores across FED subtypes, supporting the presence of shared transdiagnostic mechanisms. Conclusions: This study highlights the complex interplay between FED and psychiatric comorbidities, emphasizing the need for early intervention and personalized treatment approaches. The dimensional structure identified through PCA suggests that common psychopathological factors may drive FED development, and ANCOVA findings support their differential expression across FED types. Future research should further investigate these transdiagnostic mechanisms to optimize clinical care. Full article

Background/Objectives: Tourette syndrome (TS) is a neurodevelopmental disorder, manifested by tics and a variety of behavioral comorbidities that cluster strongly within families, suggesting a combination of genetic and environmental risk factors. The underlying pathophysiology of TS remains to be elucidated. Understanding the incidence and prevalence across different populations provides valuable insights into the etiology and pathogenesis of the condition and aids in the development of effective treatment strategies. Methods: A comprehensive literature search was conducted on PubMed covering the period from 1 January 2000 to 1 January 2025. The search used the terms “Tourette syndrome”, “tics”, “tic disorders”, “epidemiology”, “prevalence”, and “incidence”. Results: The prevalence of TS is estimated to be about 1% in children and adolescents and approximately 0.01% in adults, with a male-to-female (M:F) ratio of about 4:1. The prevalence of tic disorders is higher in all studies performed in special education populations. Conclusions: Despite substantial methodological variability, our review of the literature indicates that TS is a relatively common neurobehavioral disorder, affecting nearly 1% of children, especially boys. Raising global awareness and expanding training in TS should lead to better identification of undiagnosed patients. Full article

The current work presents the influence of the magnesiothermic synthesis method on titanium carbide (TiC). In this method, powdered titanium precursors and two carbon sources—turbostratic carbon and carbon nanotubes—were employed in proportions of 10 wt.% and 20 wt.%. The refinement of the X-ray diffraction (XRD) patterns using the Rietveld method for TiC suggests suggested coexistence of two phases, cubic with Fm-3m space group and hexagonal with P3₁21 space group. In particular, for the sample with 20 wt.% of carbon sources, the XRD refinement revealed that the cubic phase accounted for 94% of the composition, in contrast to a secondary hexagonal phase, Ti₆C_3.75, which comprised 6%. The influence of carbon on the morphology (particle size and shape) and crystallite size was monitored through bright-field transmission electron microscopy (BF-TEM) imaging and XRD. In samples containing 20 wt.% carbon, a homogeneous morphology in both size (around 11 microns) and shape was observed, along with a reduction in crystallite size (from 22.7 to 17.8 nm). Raman band analysis further revealed vibrational modes indicating that carbon induced disorder in the TiC structure. The magnesiothermic synthesis method developed in this work offers a low-cost approach of interest in the aerospace and automotive industries. Additionally, the study provides significant insights for particles used as additives or reinforcing agents to enhance the mechanical properties of metal matrix composites (MMCs). Full article

Background and Objectives: Kawasaki disease (KD) is a childhood systematic vasculitis. Emerging evidence suggests a link between KD and long-term neurological implications. This study examines the association between KD and subsequent neuropsychiatric and neurodevelopmental disorders using national health data from South Korea. Materials and Methods: Using the National Health Information Database, we identified KD patients diagnosed between 2002 and 2021 and selected those born between 2008 and 2015. Propensity score matching with a 1:4 ratio was applied to create a control group. The incidence of neuropsychiatric and neurodevelopmental disorders from 2017 to 2021 was analyzed using Cox proportional hazard models, adjusting for age, sex, and urbanicity. Results: This study included 41,806 KD subjects and 163,829 matched controls. KD was associated with an increased risk of certain neuropsychiatric disorders: anxiety disorder (HR: 1.124, 1.047–1.207), sleep-related disorder (HR: 1.257, 1.094–1.444), movement disorder (HR: 1.227, 1.030–1.461), and any neuropsychiatric disorder (HR: 1.102, 1.053–1.153). For neurodevelopmental disorders, KD patients showed a lower incidence of intellectual disability (HR: 0.747, 0.641–0.871) but an increased risk of tic disorder (HR: 1.148, 1.020–1.292). Male gender and urban residency were associated with higher incidence rates for certain conditions. Conclusions: This study demonstrates that KD patients show increased risks for anxiety, sleep-related disorder, movement disorder, and tic disorder, a reduced incidence of intellectual disability, and a higher risk of tic disorder. These findings highlight the need for long-term neurological monitoring in KD patients and provide insights into its potential neurodevelopmental impact. Full article

Background/Objectives: Asthma is one of the most common chronic diseases in children, and montelukast is widely prescribed to manage symptoms. However, concerns have emerged regarding its potential association with neuropsychiatric disorders. This study aims to investigate the impact of montelukast duration on neuropsychiatric risks in children with asthma. Methods: A cohort study was conducted using Taiwan’s National Health Insurance Research Database (NHIRD), including children diagnosed with asthma between 2004 and 2007. A total of 14,606 children in the montelukast cohort and 8432 in the non-montelukast cohort were analyzed, with propensity score matching applied to reduce confounding bias. Neuropsychiatric outcomes, including Tics/Tourette’s syndrome, were evaluated using Cox proportional hazard models. Results: Overall, montelukast use did not increase the risk of neuropsychiatric disorders. However, among children aged 6–15 years, prolonged use beyond 63 days was associated with a significantly elevated risk of Tics/Tourette’s syndrome, with a 2.6-fold increase observed in girls and a 1.8-fold increase in boys. Conversely, shorter montelukast use in children aged 0–6 years was linked to a lower risk of neuropsychiatric disorders. Conclusions: Although montelukast generally does not elevate neuropsychiatric risks, extended use in older children may increase the likelihood of developing Tics/Tourette’s syndrome. These findings highlight the importance of cautious prescribing in pediatric asthma management. Further research is necessary to validate these associations and inform clinical decision making. Full article

Background: Tourette syndrome is a neurodevelopmental disorder characterized by multiple motor and vocal tics. Although Tourette syndrome is known to have various comorbidities, comprehensive data on its prevalence and associated conditions in a large, diverse population are limited. This study aimed to examine the prevalence of Tourette syndrome and its comorbidities in children aged 3 to 17 years using data from the 2021 National Survey of Children’s Health (NSCH). Methods: Data from 79,236 children aged 3–17 years were analyzed. The prevalence of Tourette syndrome was assessed, and its association with socio-demographic factors and comorbid conditions, including prematurity and low birth weight, was examined using univariate and multivariate logistic regression models. Results: The prevalence of Tourette syndrome was 0.3% among children aged 3–17 years, with higher rates in males (74%) and adolescents aged 11–17 years (74%). Prematurity and low birth weight were associated with higher rates of Tourette syndrome and its comorbidities. Neurodevelopmental conditions such as ADHD (49% in Tourette syndrome vs. 10.2% in non-Tourette syndrome), autism spectrum disorder (21% vs. 3.2%), and learning disabilities were significantly more prevalent among children with Tourette syndrome. Similarly, psychiatric disorders such as anxiety (60% vs. 11.3%) and depression (25% vs. 5%) were more common in the Tourette syndrome group. Immune-based conditions, including asthma and allergies, and physical health conditions such as diabetes and vision or hearing problems, were also significantly associated with TS. Conclusions: The study highlights the significant burden of comorbidities in children with Tourette syndrome, emphasizing the need for early diagnosis and comprehensive management strategies to address the multifaceted challenges faced by these children. Full article