Search Results (1,412)

Background and Objectives: The attachment-diathesis model of chronic pain, which associates insecure attachment with pain catastrophizing and worse pain-related outcomes, is well-supported in adults. Although Functional Abdominal Pain Disorders (FAPDs) are common in youth, with symptoms influenced by the parent–child dynamic, an attachment-diathesis model of FAPDs is unexplored. The aim of this study was to investigate if insecure parental attachment is associated with pain catastrophizing and pain-related variables in youth with FAPDs. Methods: Baseline questionnaire data from an RCT of cognitive behavioral therapy for children with FAPDs (n = 200, 73% girls, 93% White, and a mean age of 11.2 years old) were used to examine relationships between parental attachment (subscales include Alienation, Trust, and Communication), catastrophizing, and pain-related variables (depression, disability, and gastrointestinal (GI) symptom severity). Results: Alienation was significantly correlated with depression (r = 0.39), GI symptom severity (r = 0.30), and disability (r = 0.22; ps < 0.05). Trust was also correlated with depression (r = −0.39), GI symptom severity (r = −0.19), and disability (r = −0.19; ps < 0.05). Communication was associated with depression (r = −0.30, p < 0.01). Catastrophizing mediated these associations, accounting for 22–89% of the relationship between attachment and pain-related variables. Conclusions: Children who report a less secure attachment to their parents report more physical and psychological symptomatology than children who describe their attachment as more secure. This association is partly explained by child catastrophizing. Results suggest that parent–child attachment and catastrophizing may be important treatment targets in children with FAPDs. Full article

Background/Objectives: CLIFAHDD syndrome (OMIM # 616266) is a rare neurodevelopmental disorder caused by mutations in the NALCN gene. It is characterized by hypotonia, developmental delay, and congenital contractures of the limbs and face. We report a 33-year-old Italian woman with a mild form of CLIFAHDD who exhibited early-onset language difficulties and mild intellectual disability and later developed gait and balance impairments in adulthood. Methods and Results: Whole Exome Sequencing (WES) identified a novel missense variant c.1514A>T; p.(Lys505Met) in the NALCN gene. The allele frequency of this variant is not detected (MAF = 0.0), the variant is classified as likely pathogenic according to ACMG criteria, and predicted to be probably damaging by PolyPhen-2. It affects a critical residue within the second pore-forming domain of the NALCN channel, potentially altering lipid interactions and channel regulation. Sanger sequencing and segregation analysis confirmed the variant to be heterozygous and de novo. Conclusions: The patient’s milder symptoms and later onset, compared to severe pediatric cases, suggest that the clinical spectrum of CLIFAHDD syndrome may be broader than previously recognized. These findings underscore the potential influence of mutation location on disease presentation and severity. Full article

Objectives: Chronic pain corresponds to hypersensitivity to painful stimuli; however, its relation to acute pain sensitivity in children is poorly understood. We explored this relationship by comparing acute and chronic pain measures, along with related factors, in children with chronic pain syndromes versus controls, before and after therapeutic intervention. Methods: This prospective controlled cohort study involved 57 children with chronic pain undergoing intensive interdisciplinary pain treatment in a hospital-based pain rehabilitation program and 50 controls. Participants, aged 7–18, were tested using a cold pressor task (CPT) at admission, discharge, and first follow-up visit. Data on sleep, anxiety, psychological distress, functional impairment, and pain were collected. Results: Significant differences were found between control and treatment groups in average pain threshold (p < 0.001), pain tolerance (p = 0.035), sleep visual analog scale (VAS) (p < 0.001), functional disability inventory (p < 0.001), patient reported outcomes information system anxiety assessment tool (p < 0.001), general anxiety disorder 7-item scale (p < 0.001), pain VAS (p < 0.001) and total brief symptom inventory (BSI) (p < 0.001) scores at admission with children with chronic pain scoring worse on all measures save the pain VAS during the CPT. After treatment and at follow-up, function and mental health measures improved but not acute pain threshold. Conclusions: At treatment completion, function and mental health significantly improved but acute pain threshold and sleep quality were unchanged. These findings suggest that while chronic pain treatment improves overall function and mental health, acute pain thresholds may not be a suitable indicator for evaluating the efficacy of interventions. Full article

Background: Autosomal dominant intellectual developmental disorder 51 (MIM #617788) is caused by pathogenic variants in KMT5B, a histone methyltransferase essential for transcriptional repression and central nervous system development. The disorder manifests as a complex neurodevelopmental syndrome with variable neurological and systemic features. Methods: Two adolescents with nonsense KMT5B variants underwent detailed clinical, neuropsychological, and neuroimaging evaluations, including MRI and ¹⁸FDG PET/CT, analyzed with Statistical Parametric Mapping against matched controls. RNA sequencing was performed, and the literature was reviewed to assess genotype–phenotype correlations. Results: Both patients showed global developmental delay, progressing to autism spectrum disorder (ASD) and developmental coordination disorder (DCD), without intellectual disability (ID). The MRI was normal, but neuropsychological testing revealed executive function impairment, expressive language deficits, and behavioral disturbances. PET/CT consistently demonstrated cerebellar and temporal lobe hypometabolism, correlating with symptom severity. RNA sequencing identified shared dysregulated pathways, notably DDIT4 upregulation, linked to synaptic dysfunction and neuronal atrophy in animal models. Conclusions: The findings highlight cerebellar involvement in DCD and ASD, medial temporal lobe contribution to ASD and executive dysfunction, and DDIT4 as a possible molecular signature of KMT5B loss-of-function. An integrative multimodal approach refined genotype–phenotype correlations and revealed novel brain regions and pathways implicated in KMT5B-related disorders. Full article

This study applies psychological network analysis to explore the structure and dynamics of parental stress, offering a novel perspective beyond traditional latent variable approaches. Rather than treating parental stress as a unidimensional construct, network analysis conceptualizes it as a system of interrelated emotional, behavioral, and contextual symptoms. Using cross-sectional data from Latinx parents of children with intellectual and developmental disabilities (IDD), we compared and identified key central and bridge stress symptoms of Latinx parents of children with autism versus other disabilities that hold influential positions within the stress network. These findings suggest that certain stressors may act as hubs, reinforcing other stress components and potentially serving as high-impact targets for intervention. Network analysis also highlights how symptom relationships vary by types of disabilities, offering insight into tailored support strategies. Overall, this approach provides a dynamic and clinically actionable framework for understanding parental stress, with implications for assessment, early intervention, and personalized mental health care for parents. Full article

Chronic pelvic neuropathies involving the pudendal, ilioinguinal, and genitofemoral nerves are a major source of refractory pain and disability, yet conventional steroid injections typically provide only short-lived benefit. We retrospectively analyzed 78 patients: 49 with pudendal neuralgia treated by pulsed radiofrequency and 29 with ilioinguinal (n = 15) or genitofemoral (n = 14) neuropathies treated by continuous radiofrequency ablation. For pudendal neuropathy, pRF provided a mean pain relief of 9.48 ± 9.52 weeks versus 3.98 ± 3.56 weeks after the first steroid injection and 3.32 ± 3.21 weeks after the most recent (p < 0.0001 for both). Quality-of-life scores improved significantly through 3 months, and analgesic use declined during this period. No correlation was found between symptom duration and treatment response. For ilioinguinal and genitofemoral neuropathies, cRFA extended pain relief to 21.76 and 17.68 weeks, respectively. Mean VAS scores improved from 6.87 to 1.73 for ilioinguinal (p < 0.0001) and from 6.36 to 2.36 for genitofemoral (p = 0.0007) neuropathies. Quality-of-life scores improved through 3 months, with trends toward baseline by 6 months, while analgesic use decreased initially before returning to baseline. Across all nerves, no major complications occurred. Radiofrequency treatment offers safe, longer-lasting relief than steroid injections for refractory pelvic neuropathies. Full article

Schizophrenia (SZ) is a severe mental disorder associated with an array of symptoms characterized as positive, negative and cognitive dysfunctions. While SZ is a multifaceted disorder affecting several regions of the brain, altered thalamocortical systems have emerged as a leading contributor to SZ. Specifically, it has been shown that: (1) the thalamus is functionally disconnected from the prefrontal cortex (PFC) in SZ; (2) neural activity and blood flow to the PFC are greatly diminished in SZ (hypofrontality); and (3) delta oscillations are abnormally present in the PFC during the waking state in SZ. We suggest that the abnormal delta oscillations drive the other PFC signs of SZ. Specifically, decreases in energy required to maintain delta, would initiate the reduced PFC perfusion of SZ (hypofrontality), and contribute to the ‘mismatched’ thalamic and PFC activity of SZ. As SZ involves glutamate (NMDAR) hypofunction and dopamine hyperfunction, both NMDAR antagonists and dopamine agonists produce marked increases in delta oscillations in nucleus reuniens (RE) of the thalamus and its target structures, including the PFC. This would suggest that RE is a primary source for the elicitation of PFC delta activity, and the presence of delta during waking (together with associated signs) would indicate that the prefrontal cortex is disabled (or non-functional) in schizophrenia. Full article

Major depressive disorder (MDD) is a prevalent and disabling condition. Transcranial direct current stimulation (tDCS) may improve symptoms by modulating neuroplastic and inflammatory mechanisms. This randomized, double-blind, placebo-controlled trial will recruit adult outpatients with MDD showing residual symptoms despite at least four weeks of stable SSRI treatment. Participants will be randomized to active or sham add-on tDCS while continuing their antidepressant regimen. The intervention will consist of 15 sessions over 3 weeks, targeting the left dorsolateral prefrontal cortex (anode F3, cathode F4) at 2 mA for 30 min per session. The primary outcome is the reduction of depressive symptoms measured by the Hamilton Depression Rating Scale-17 (HDRS), with remission defined as HDRS-17 ≤ 7. Secondary outcomes include cognitive performance (attention, executive functioning, memory), serum biomarkers (BDNF, VEGF, NGF, NRG1, angiogenin, IGF1, IL-6, TNF-α), cortical excitability assessed by transcranial magnetic stimulation (motor threshold, silent period, intracortical inhibition/facilitation), and cerebral hemodynamics by transcranial Doppler sonography (blood flow velocity, pulsatility, resistivity). Assessments will occur at baseline, post-treatment, and 3- and 6-month follow-ups. This trial aims to evaluate the efficacy of adjunctive tDCS in MDD with residual symptoms and its biological correlates, bridging clinical improvement with electrophysiological and neurovascular mechanisms. Full article

Background/Objectives: This study aimed to establish a method for evaluating the pathology of lateral elbow tendinopathy (LET) using ultrasonography. Methods: The LET group consisted of 47 patients with 50 elbows, and the control group consisted of 50 healthy adults with 50 elbows. The variables used for the pathological classification of LET included the peak systolic velocity (PSV) of the radial recurrent artery (RRA), fiber orientation intensity, numeric rating scale (NRS), Disabilities of the Arm, Shoulder, and Hand (DASH) score, and duration of symptoms. Classification was performed using principal component and cluster analyses. Results: The PSV of the RRA was significantly higher in the LET group (19.10 ± 4.63 cm/s) than in the control group (16.04 ± 2.96 cm/s). The fiber orientation intensity was significantly lower in the LET group (1.62 ± 0.15) than in the control group (1.73 ± 0.12). LET can be classified into three clusters. Cluster 1 showed decreased fiber orientation and moderate NRS and DASH scores. Cluster 2 demonstrated increased PSV of the RRA and severe NRS and DASH scores. Cluster 3 maintained a normal PSV of the RRA and fiber orientation, with mild NRS and DASH scores. No statistically significant differences were noted in the duration of symptoms between clusters. However, symptom duration tended to be longer in Clusters 1, 2, and 3. Conclusions: This study suggests that LET can be classified into mild, inflammatory, and degenerative phases. Full article

Background/Objectives: Juvenile Idiopathic Arthritis (JIA) is the most common autoimmune rheumatic disease in children and can vary in presentation based on the properties of the JIA subtypes. Timely diagnosis and intervention are essential for maximizing quality of life, healthy growth and development, and prevention of long-term disability. This review aims to provide a clinically practical framework for the core elements important in recognition, monitoring, and management of JIA. Methods: We performed a narrative review of the current literature, complemented by real-world clinical experience from academic rheumatology practice. The review synthesizes evidence-based knowledge with practical insights to develop an approach that can be applied in daily clinical decision-making. Results: We propose a structured, stepwise method for evaluating suspected JIA, emphasizing the integration of pattern recognition with differential diagnosis. Our framework emphasizes two principal parameters: (1) the distribution of joint involvement (peripheral vs. axial) and (2) the presence of extra-articular manifestations, including uveitis, cutaneous findings, and gastrointestinal symptoms. This format aids in distinguishing major JIA subtypes and highlights their distinctive features. In addition, we review overarching principles for monitoring, assessing risk for uveitis, and treatment, and the importance of multidisciplinary care. Conclusions: This structured approach is intended to support clinicians in the accurate recognition of JIA and its subtypes, facilitate early diagnosis, and provide insights on management strategies that improve patient outcomes. Full article

Knee osteoarthritis (OA) is a complex condition with varying pain, functional limitations, and structural changes. Traditional classification using radiographic grades may not fully reflect individual patient experiences. This study aimed to establish WOMAC score cut-offs for KL grades and identify knee OA phenotypes through cluster analysis in a cohort of 99 adults, examining functional and radiological status, factors such as age, sex, body mass index (BMI), comorbidities, and psychological status. Receiver operating characteristic (ROC) analysis helped establish WOMAC cut-off scores related to KL grades, and cluster analysis identified phenotypic subgroups. The analysis showed that higher WOMAC scores correlated with advanced KL grades, leading to a five-tier classification of symptomatic severity: minimal or no symptoms (≤24), mild (25–41), moderate (42–69), severe (70–86), and extreme (≥87). Cluster analysis identified four distinct phenotypic groups: (1) younger patients exhibiting minimal symptoms and low KL grades; (2) individuals with moderate disease are characterized by functional deficits; (3) patients presenting with moderate-to-severe symptoms and significant joint narrowing; and (4) a subgroup experiencing severe pain, high levels of disability, advanced KL grades, elevated psychological distress, and an increased BMI. The study supports WOMAC cut-offs as key indicators of knee OA severity and shows that cluster analysis can reveal distinct phenotypes, underscoring the need for personalized management strategies in knee OA treatment. Full article

Background/Objectives: Behavioral variant frontotemporal dementia (bvFTD), the most prevalent clinical subtype within the frontotemporal lobar degeneration spectrum disorders, is characterized by early and prominent changes that significantly disrupt everyday functioning. This study aims to identify the key correlates of functional status in bvFTD by investigating the relative contributions of cognitive deficits, behavioral disturbances, personality changes, and brain perfusion abnormalities. Additionally, it seeks to develop a theoretical framework to elucidate how these factors may interconnect and shape unique functional profiles. Methods: A total of 26 individuals diagnosed with bvFTD were recruited from the 2nd Neurology Clinic of “AHEPA” University Hospital in Thessaloniki, Greece, and underwent a comprehensive neuropsychological assessment to evaluate their cognitive functions. Behavioral disturbances, personality traits, and functional status were rated using informant-based measures. Regional cerebral blood flow was assessed using Single Photon Emission Computed Tomography (SPECT) imaging to evaluate brain perfusion patterns. Penalized Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was performed to identify the most robust correlates of functional impairment, followed by path analyses using structural equation modeling to explore how these factors may interrelate and contribute to functional disability. Results: The severity of negative behavioral symptoms (e.g., apathy), conscientiousness levels, and performance on neuropsychological measures of semantic verbal fluency, visual attention, visuomotor speed, and global cognition were identified as the strongest correlates of performance in activities of daily living. Neuroimaging analysis revealed hypoperfusion in the right prefrontal (Brodmann area 8) and inferior parietal (Brodmann area 40) cortices as statistically significant neural correlates of functional impairment in bvFTD. Path analyses indicated that reduced brain perfusion was associated with attentional and processing speed deficits, which were further linked to more severe negative behavioral symptoms. These behavioral disturbances were subsequently correlated with declines in global cognition and conscientiousness, which were ultimately associated with poorer daily functioning. Conclusions: Hypoperfusion in key prefrontal and parietal regions, along with the subsequent cognitive and neuropsychiatric manifestations, appears to be associated with the pronounced functional limitations observed in individuals with bvFTD, even in early stages. Understanding the key determinants of the disease can inform the development of more targeted, personalized treatment strategies aimed at mitigating functional deterioration and enhancing the quality of life for affected individuals. Full article

γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS), regulates neuronal excitability, synaptic plasticity, and oscillatory activity essential for cognition, emotion, and behavior. Disruptions in GABAergic signaling are increasingly recognized as key contributors to a range of neurodevelopmental disorders (NDDs), including schizophrenia (SZ), autism spectrum disorder (ASD), major depressive disorder (MDD), bipolar disorder (BD), and intellectual disability (ID). In this review, we analyze the data available from the literature concerning the components of the GABA pathway. We describe the main steps of GABA metabolism, including GABA synthesis and release, GABA receptors neurotransmission, GABA reuptake and catabolism, and evaluate their involvement in the pathogenesis of neurodevelopmental disorders. We suggest the possibility of existence of so far undescribed mechanisms which maintain the concentrations of GABA at a relatively physiological level when the function of glutamic acid decarboxylases is compromised by mutations. Searching for these mechanisms could be important for better understanding neurodevelopment and could give a clue for future searches for new therapeutic approaches for treating or alleviating the symptoms of BD and SZ. We also argue that the metabolic stage of the GABA pathway has only a minor direct effect on GABA signaling and rather causes clinical effects due to accumulation of neurotoxic byproducts. Full article

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder in which early diagnosis improves quality of life and reduces disability. However, diagnostic delays remain common, particularly in low- and middle-income countries. This study investigated clinical and system-level factors contributing to diagnostic delay in Thailand. Methods: A retrospective chart review was conducted on patients newly diagnosed with PD at Thammasat University Hospital between June 2020 and June 2024. Demographic, clinical, and healthcare access data were analyzed. Diagnostic intervals were defined as onset-to-visit (OTV), visit-to-diagnosis (VTD), and onset-to-diagnosis (OTD). Age-at-onset groups included early-onset Parkinson’s disease (EOPD, <50 years), regular-onset PD, and very-late-onset PD (≥80 years). Results: Of 1093 patients screened, 109 newly diagnosed PD cases met the inclusion criteria. The median OTV was 360 days, and the median VTD was 10 days. Tremor was the most frequent initial symptom (75%). Patients with higher education and extended family support sought care earlier, whereas those under the Universal Coverage Scheme (UCS) experienced longer OTD durations (median, 541 vs. 181 days in privately insured patients). More than half of patients were initially misdiagnosed, especially when first evaluated by non-neurologists. Conclusions: Diagnostic delay in Thai PD patients stems mainly from late help-seeking and inequities in healthcare access. Addressing these gaps requires public awareness, physician training, streamlined UCS referral pathways, and adoption of biomarker-supported digital tools to ensure earlier and more equitable diagnosis. Full article

Background/Objectives: Multiple sclerosis (MS) is an autoimmune disorder affecting the central nervous system, characterised by the degradation of myelin, which results in various neurological symptoms. This study aims to utilise radiomics features to evaluate the predictive value of IVIM diffusion parameters, namely, the true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f), in relation to disability severity, assessed using the Expanded Disability Status Scale (EDSS), and mobility in patients with relapsing–remitting MS. Methods: This retrospective cross-sectional study analysed MRI data from 197 patients diagnosed with multiple sclerosis (MS). Quantitative intravoxel incoherent motion (IVIM) parameters were obtained using a 1.5 Tesla MRI scanner. Clinical information collected included age, disease duration, number of relapses, status of disease-modifying therapy (DMT), and the need for mobility assistance. Machine learning (ML) techniques, such as XGB, Random Forest, and ANN, were employed to explore the relationships between radiomic IVIM parameters and these clinical variables. Results: IVIM radiomics achieved high accuracy in lesion phenotyping. Random Forest distinguished enhancements from non-enhancing lesions with 96% accuracy and AUC = 0.99 with IVIM-f and D* maps. CNN also reached ~92% accuracy (AUC 0.97) with IVIM-f. For disability prediction, IVIM-D and D* radiomics strongly correlated with EDSS: Random Forest achieved 89% accuracy (AUC = 0.90), while CNN achieved 90% accuracy (AUC = 0.95). Mobility impairment was predicted with the highest performance—RNN achieved 96% accuracy (AUC = 0.99) across IVIM-f features. In contrast, relapse history, disease duration, and treatment status were poorly predicted (<75% accuracy). Conclusions: ML analyses of IVIM metrics provided independent predictors of functional impairment and disability in MS. Our novel approach may be used to improve diagnostic accuracy and develop personalised treatment strategies for MS patients. Full article