Search Results (2,653)

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that utilizes magnetic fields to induce cortical electric currents, enabling both the measurement and modulation of neuronal activity. Initially developed as a diagnostic tool, TMS now serves dual roles in clinical neurology, offering insight into neurophysiological dysfunctions and the therapeutic modulation of abnormal cortical excitability. This review examines key TMS outcome measures, including motor thresholds (MT), input–output (I/O) curves, cortical silent periods (CSP), and paired-pulse paradigms such as short-interval intracortical inhibition (SICI), short-interval intracortical facilitation (SICF), intracortical facilitation (ICF), long interval cortical inhibition (LICI), interhemispheric inhibition (IHI), and short-latency afferent inhibition (SAI). These biomarkers reflect underlying neurotransmitter systems and can aid in differentiating neurological conditions. Diagnostic applications of TMS are explored in Parkinson’s disease (PD), dystonia, essential tremor (ET), Alzheimer’s disease (AD), and mild cognitive impairment (MCI). Each condition displays characteristic neurophysiological profiles, highlighting the potential for TMS-derived biomarkers in early or differential diagnosis. Therapeutically, repetitive TMS (rTMS) has shown promise in modulating cortical circuits and improving motor and cognitive symptoms. High- and low-frequency stimulation protocols have demonstrated efficacy in PD, dystonia, ET, AD, and MCI, targeting the specific cortical regions implicated in each disorder. Moreover, the successful application of TMS in differentiating and treating AD and MCI underscores its clinical utility and translational potential across all neurodegenerative conditions. As research advances, increased attention and investment in TMS could facilitate similar diagnostic and therapeutic breakthroughs for other neurological disorders that currently lack robust tools for early detection and effective intervention. Moreover, this review also aims to underscore the importance of maintaining standardized TMS protocols. By highlighting inconsistencies and variability in outcomes across studies, we emphasize that careful methodological design is critical for ensuring the reproducibility, comparability, and reliable interpretation of TMS findings. In summary, this review emphasizes the value of TMS as a distinctive, non-invasive approach to probing brain function and highlights its considerable promise as both a diagnostic and therapeutic modality in neurology—roles that are often considered separately. Full article

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by motor dysfunction and non-motor symptoms, including cognitive decline. Animal models that replicate PD’s clinical features are essential for therapeutic research. The widely used subacute 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-induced mouse model effectively mimics motor deficits but fails to fully represent aging-related non-motor symptoms. In this study, we established an aging-associated PD mouse model by combining MPTP with D-galactose treatment. Compared to mice treated with MPTP alone, MPTP + D-galactose-treated mice exhibited typical motor impairments alongside cognitive deficits in the Morris water maze and Y-maze tests. D-galactose alone induced cognitive impairment without motor dysfunction. Pathological analysis showed that the MPTP + D-galactose treatment caused tyrosine hydroxylase-positive neuron loss similar to MPTP, while D-galactose did not damage these neurons. Additionally, Micro-CT revealed bone loss in both the MPTP + D-galactose and D-galactose groups. This model recapitulates both the motor and aging-related non-motor symptoms of PD, including cognitive impairment and bone loss, providing a more comprehensive tool for studying PD pathogenesis and evaluating potential therapies. Full article

Background: Craniocervical pain and temporomandibular disorders (TMDs) are prevalent, interconnected conditions. While Movement Representation Techniques (MRTs) are cognitive interventions targeting central pain mechanisms, their specific efficacy here lacks synthesis. This study systematically analyzes the effectiveness of MRTs, such as motor imagery (MI) and action observation (AO), on pain and function in individuals with craniocervical and orofacial pain. Methods: A systematic review of RCTs (PROSPERO: CRD420251155428) was conducted following PRISMA guidelines. Four databases were searched for studies applying MRTs (MI, AO, laterality discrimination) to adults with craniocervical or orofacial pain. Primary outcomes were pain and functionality. Methodological quality was assessed using the PEDro scale and Cochrane RoB 2 tool. Results: Eight RCTs (n = 362) were included. Methodological quality was high (PEDro scores 8–9). MRTs significantly increased Pressure Pain Threshold (PPT) in the masseter, trapezius, and cervical regions. Functional improvements included enhanced cervical range of motion and sensorimotor control. AO consistently demonstrated superior outcomes. However, results for orofacial variables were derived from asymptomatic subjects. Results for cervical muscle strength were inconsistent. Conclusions: MRTs, especially AO, show potential to reduce pain and improve function in craniocervical disorders. Evidence in symptomatic orofacial pain populations is non-existent. Protocol heterogeneity and limited research groups necessitate further high-quality, multicenter RCTs to establish robust clinical guidelines. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by the degeneration of dopaminergic neurons in the substantia nigra, resulting in cardinal motor symptoms such as tremor, rigidity, and bradykinesia. Neuroinflammation is increasingly recognized as a central driver of PD onset and progression in which oligodendrocytes, astrocytes, and microglia engage in complex bidirectional crosstalk that shapes the inflammatory milieu of the central nervous system. Pathological activation of glial cells triggers the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species, thereby exacerbating neuronal injury and contributing to sustained disease progression. Modulating maladaptive glial activation states and their intercellular communication represents a promising therapeutic avenue aimed at mitigating neuroinflammation and slowing PD pathology. This review synthesizes current knowledge on neuroinflammation in PD, focusing on the distinct roles of microglia, astrocytes, and oligodendrocytes, their interaction networks, and emerging therapeutic strategies. Full article

Vision is fundamental to the acquisition of motor, cognitive, and social skills, playing a crucial role in typical development. Early visual impairments are associated with various neurodevelopmental conditions, including Autism Spectrum Disorder (ASD). The (Brain-specific serine/threonine-protein kinase 2, BRSK2) gene has been identified as a high-risk gene for ASD. This study aims to investigate the role of brsk2 in retinal photoreceptor development and visual function in zebrafish. Using behavioral assays, histological analysis, and transcriptomic profiling, we assessed the impact of brsk2 deletion on retinal structure and function. The results showed that brsk2ab^−/− zebrafish larvae exhibited significantly enhanced light perception compared to wild-type (WT) controls. Structural analysis of the retina revealed disruptions in the layered organization, along with up-regulated rhodopsin expression in retinal cells. Additionally, transcriptomic analysis indicated that key opsins and genes involved in visual development and phototransduction pathways were markedly up-regulated following brsk2 deletion. This research highlights the importance of brsk2 in early retinal circuit development and its potential implications for understanding sensory processing deficits in neurodevelopmental disorders. By linking BRSK2 to specific sensory phenotypes, this study addresses a critical gap in knowledge regarding the mechanisms underlying sensory abnormalities in ASD and related conditions. Full article

New wearable technology opens new possibilities for low-cost, easily accessible home-based interventions as a supplement to typical clinical rehabilitation therapy. In this pilot study, we tested a new interactive adjustable Feedback training system on 14 infants at high risk of cerebral palsy between 2 and 12 months of age to facilitate increased movements. The system consists of four wireless motion sensors placed on the infant’s limbs. Inertial sensors track the infant’s movements which control auditory and visual stimuli that act as motivational feedback. A 15 min usage of the Feedback training system four days a week for approximately six months was aimed for. None of the participants reached the recommended amount of intervention, due to time limitations. Seven of the twelve participating infants (58%) achieved at least 50% of the recommended training amount. Parents found the Feedback training system easy to use with minimal need for technical assistance. Preliminary data suggest that infants engaged more actively during training sessions where their movements actively controlled the presentation of the stimuli. The Feedback training system is promising as a user-friendly add-on to the playful and interactive stimulation of motor and cognitive development in infants with neurodevelopmental disorders. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by age-dependent degeneration of dopaminergic neurons in the substantia nigra, a process mediated by α-synuclein aggregation, mitochondrial dysfunction, and impaired proteostasis. While BAP31—an endoplasmic reticulum protein critical for protein trafficking and degradation—has been implicated in neuronal processes, its role in PD pathogenesis remains poorly understood. To investigate the impact of BAP31 deficiency on PD progression, we generated dopamine neuron-specific BAP31 conditional knockout with DAT-Cre (cKO) mice (Slc6a3cre-BAP31^fl/fl) and subjected them to MPTP-lesioned Parkinsonian models. Compared to BAP31^fl/fl controls, Slc6a3cre-BAP31^fl/fl mice exhibited exacerbated motor deficits following MPTP treatment, including impaired rotarod performance, reduced balance beam traversal time, and diminished climbing and voluntary motor capacity abilities. BAP31 conditional deletion showed no baseline phenotype, with deficits emerging only after MPTP. Our results indicate that these behavioral impairments correlated with neuropathological hallmarks: decreased NeuN neuronal counts, elevated GFAP astrogliosis, reduced tyrosine hydroxylase levels in the substantia nigra, and aggravated dopaminergic neurodegeneration. Mechanistically, BAP31 deficiency disrupted mitochondrial homeostasis by suppressing the PINK1–Parkin mitophagy pathway. Further analysis revealed that BAP31 regulates PINK1 transcription via the transcription factor Engrailed Homeobox 1. Collectively, our findings identify BAP31 as a neuroprotective modulator that mitigates PD-associated motor dysfunction by preserving mitochondrial stability, underscoring its therapeutic potential as a target for neurodegenerative disorders. Full article

Analyzing the dynamics of muscle activation patterns and joint range of motion is essential to understanding human movement during complex tasks such as tooth brushing Activities of Daily Living (ADLs). In individuals with neuromotor impairments, accurate assessment of upper limb motor patterns plays a critical role in rehabilitation, supporting the identification of compensatory strategies and informing clinical interventions. This study presents the validation of a previously developed novel, low-cost, wearable, and portable multimodal prototype that integrates inertial measurement units (IMU) and surface electromyography (sEMG) sensors into a single device. The system enables bilateral monitoring of arm segment kinematics and muscle activation amplitudes from six major agonist muscles during ADLs. Eleven healthy participants performed a functional task, tooth brushing, while wearing the prototype. The recorded data were compared with two established gold-standard systems, Qualisys^® motion capture system and Biosignalsplux^®, for validation of kinematic and electrophysiological measurements, respectively. This study provides technical insights into the device’s architecture. The developed system demonstrates potential for clinical and research applications, particularly for monitoring upper limb function and evaluating rehabilitation outcomes in populations with neurological disorders. Full article

Down Syndrome Regression Disorder (DSRD) is a rare but severe neuropsychiatric condition characterized by abrupt loss of speech, autonomy, and cognitive abilities in individuals with Down syndrome, often associated with immune dysregulation and gut–brain axis dysfunction. We report the case of an 11-year-old girl with Down syndrome who developed developmental regression at age five, in temporal proximity to a family transition (the birth of a younger sibling), with loss of continence, language, and comprehension, alongside persistent behavioral agitation and gastrointestinal symptoms. Laboratory assessment revealed Giardia duodenalis infection, elevated fecal calprotectin and secretory IgA, and microbial imbalance with overgrowth of Streptococcus anginosus and S. sobrinus. The patient received a single oral dose of tinidazole (2 g), daily folinic acid (1 mg/kg), and a 90-day course of transcranial and abdominal photobiomodulation (PBM) (1064 nm, 10 min per site). Post-treatment, stool analysis showed normalized inflammation markers and restoration of beneficial bacterial genera (Bacteroides, Bifidobacterium, Lactobacillus) with absence of Enterococcus growth. Behaviorally, she exhibited marked recovery: CARS-2-QPC decreased from 106 to 91, ABC from 63 to 31, and ATEC from 62 to 57, alongside regained continence, speech, and fine-motor coordination. These outcomes suggest that abdominal and transcranial PBM, by modulating mitochondrial metabolism, mucosal immunity, and microbiota composition, may facilitate systemic and neurobehavioral recovery in DSRD. This translational case supports further investigation of PBM as a non-invasive, multimodal therapy for neuroimmune regression in genetic and developmental disorders including validation through future randomized controlled clinical trials. Full article

Dysphagia and dysarthria are common, co-occurring manifestations in neurodegenerative diseases, resulting from damage to distributed neural networks involving cortical, subcortical, cerebellar, and brainstem regions. These disorders profoundly affect patient health and quality of life through complex sensorimotor impairments. Objective: The aims was to provide a comprehensive, evidence-based review of the neuroanatomical substrates, pathophysiology, diagnostic approaches, and management strategies for dysphagia and dysarthria in neurodegenerative diseases with emphasis on their multisystem nature and integrated treatment approaches. Methods: A narrative literature review was conducted using PubMed, Scopus, and Web of Science databases (2000–2024), focusing on Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). Search terms included “dysphagia”, “dysarthria”, “neurodegenerative diseases”, “neural networks”, “swallowing control” and “speech production.” Studies on neuroanatomy, pathophysiology, diagnostic tools, and therapeutic interventions were included. Results: Contemporary neuroscience demonstrates that swallowing and speech control involve extensive neural networks beyond the brainstem, including bilateral sensorimotor cortex, insula, cingulate gyrus, basal ganglia, and cerebellum. Disease-specific patterns reflect multisystem involvement: PD affects basal ganglia and multiple brainstem nuclei; ALS involves cortical and brainstem motor neurons; MSA causes widespread autonomic and motor degeneration; PSP produces tau-related damage across multiple brain regions. Diagnostic approaches combining fiberoptic endoscopic evaluation, videofluoroscopy, acoustic analysis, and neuroimaging enable precise characterization. Management requires multidisciplinary Integrated teams implementing coordinated speech-swallowing therapy, pharmacological interventions, and assistive technologies. Conclusions: Dysphagia and dysarthria in neurodegenerative diseases result from multifocal brain damage affecting distributed neural networks. Understanding this multisystem pathophysiology enables more effective integrated assessment and treatment approaches, enhancing patient outcomes and quality of life. Full article

Background and Objectives: Evidence on motor performance in children with autism spectrum disorder (ASD) is scarce and inconsistent. The association of motor impairments with autism severity and intelligence remains insufficiently studied. We aimed to examine motor performance parameters in children with ASD compared with typically developing (TD) peers. Materials and Methods: In this cross-sectional study, a convenience sample of 26 children with ASD, aged 4–10 years, was recruited from specialized centers in KSA, alongside 27 age- and sex-matched TD children. For the ASD group, severity (Childhood Autism Rating Scale, CARS-2) and intelligence quotient (Stanford–Binet Intelligence Scale, SB5) were extracted from medical records. CARS-2 score was utilized to categorize children with ASD into two groups (mild-to-moderate and severe groups). All study children were assessed for gross and fine motor skills using the Movement Assessment Battery for Children-2 (MABC-2), balance, muscle strength, endurance, and flexibility. Results: ASD groups recorded significantly lower scores in all MABC-2 component areas when compared to the TD group (p < 0.001). Aiming and catching percentile was significantly lower in the severe ASD group compared to the mild-to-moderate group (p = 0.05). Furthermore, children with ASD exhibited increased hypermobility, predominantly at the elbow joints, reduced grip strength, shorter distance in the modified 6 min walk test, and lower standing long-jump performance (p < 0.001) when compared to TD group; however, no significant difference was recorded between the ASD groups. Spearman correlation revealed that aiming and catching was negatively correlated with autism severity (CARS-2) (r = −0.38, p = 0.05) and positively with IQ (r = 0.51, p = 0.03). Aiming and catching was positively correlated with grip strength (r = 0.55, p = 0.003), endurance (r = 0.58, p = 0.002), and jump distance (r = 0.44, p = 0.03), while balance was positively correlated with grip strength (r = 0.44, p = 0.02). Conclusions: Children with ASD exhibit significant impairments in gross and fine motor performance compared with TD peers, accompanied by hypermobility, reduced strength, and diminished endurance. Notably, aiming and catching ability correlated with both IQ and autism severity as well as specific motor parameters, suggesting its potential as a clinical marker of motor–cognitive interaction in ASD. Full article

Total hip arthroplasty (THA) is a widely performed procedure that significantly enhances patients’ quality of life. However, nerve injury remains a concerning complication, with an incidence ranging from 0.6% to 3.7%, depending on patient and surgical variables. This narrative review provides a comprehensive overview of nerve injuries associated with THA, focusing on etiology, risk factors, clinical manifestations, prevention, and treatment strategies. The most affected nerves include the sciatic, femoral, lateral femoral cutaneous (LFCN), superior gluteal, and obturator nerves. Anatomical factors such as developmental hip dysplasia (DDH), limb length discrepancy, and aberrant nerve courses, along with patient-specific conditions like female sex, obesity, and pre-existing spinal disorders, increase the risk of nerve damage. Surgical complexity, revision procedures, and surgeon experience also influence injury likelihood. Clinical manifestations range from sensory disturbances to motor deficits including foot drop, Trendelenburg gait, or impaired knee extension, depending on the nerve involved. Diagnosis is primarily clinical, supported by electrophysiological studies and imaging when needed. Prevention hinges on careful preoperative planning, appropriate surgical approach selection, meticulous intraoperative technique, and attention to limb positioning. Treatment is typically conservative, involving pain control, physical therapy, and neurostimulation. In refractory or severe cases, interventions such as nerve decompression, repair, or tendon transfer may be considered. Pharmacological agents including vitamin B12, tacrolimus, and melatonin show potential in promoting nerve regeneration. Although most nerve injuries resolve spontaneously or with conservative measures, some cases may result in long-term deficits. Understanding the mechanisms, risk factors, and management strategies is essential to mitigating complications and optimizing functional outcomes in patients undergoing THA. Full article

Background: Irisin, an exercise-induced myokine, has emerged as a potent neuroprotective factor, though a systematic synthesis of its role across neurological disorders is lacking. This review systematically evaluates clinical and preclinical evidence on irisin’s association with neurological diseases and its underlying mechanisms. Methods: Following PRISMA 2020 guidelines, a systematic search of PubMed/MEDLINE, Scopus, Web of Science, Embase, and Cochrane Library was conducted. The review protocol was prospectively registered in PROSPERO. Twenty-one studies were included, comprising predominantly preclinical evidence (n = 14), alongside clinical observational studies (n = 6), and a single randomized controlled trial (RCT) investigating irisin in cerebrovascular diseases, Parkinson’s disease (PD), Alzheimer’s disease (AD), and other neurological conditions. Eligible studies were original English-language research on irisin or FNDC5 and their neuroprotective effects, excluding reviews and studies without direct neuronal outcomes. Risk of bias was independently assessed using SYRCLE, the Newcastle–Ottawa Scale, and RoB 2, where disagreements between reviewers were resolved through discussion and consensus. Results were synthesized narratively, integrating mechanistic, pre-clinical, and clinical evidence to highlight consistent neuroprotective patterns of irisin across disease categories. Results: Clinical studies consistently demonstrated that reduced circulating irisin levels predict poorer outcomes. Lower serum irisin was associated with worse functional recovery and post-stroke depression after ischemic stroke, while decreased plasma irisin in PD correlated with greater motor severity, higher α-synuclein, and reduced dopamine uptake. In AD, cerebrospinal fluid irisin levels were significantly correlated with global cognitive efficiency and specific domain performance, and correlation analyses within studies suggested a closer association with amyloid-β pathology than with markers of general neurodegeneration. However, diagnostic accuracy metrics (e.g., AUC, sensitivity, specificity) for irisin as a standalone biomarker are not yet established. Preclinical findings revealed that irisin exerts neuroprotection through multiple mechanisms: modulating microglial polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype, suppressing NLRP3 inflammasome activation, enhancing autophagy, activating integrin αVβ5/AMPK/SIRT1 signaling, improving mitochondrial function, and reducing neuronal apoptosis. Irisin administration improved outcomes across models of stroke, PD, AD, postoperative cognitive dysfunction, and epilepsy. Conclusions: Irisin represents a critical mediator linking exercise to brain health, with consistent neuroprotective effects across diverse neurological conditions. Its dual ability to combat neuroinflammation and directly protect neurons, demonstrated in preclinical models, positions it as a promising therapeutic candidate for future investigation. Future research must prioritize the resolution of fundamental methodological challenges in irisin measurement, alongside investigating pharmacokinetics and sex-specific effects, to advance irisin toward rigorous clinical evaluation. Full article

Background/Objectives: Cluttering in childhood and adolescence is characterised by unstable speech timing, excessive coarticulation, irregular rate and reduced intelligibility, yet the developmental mechanisms underpinning these behaviours remain partially understood. This review synthesises empirical and conceptual evidence to examine cluttering through the lenses of speech motor development, neurocognitive mechanisms, task demands and allied-health practice. Four research questions guided the review, focusing on motor characteristics, developmental and neurocognitive mechanisms, task dependence and clinical implications. Methods: Following the PRISMA guidelines, a comprehensive search across seven databases identified studies examining cluttering in children and adolescents. Screening and full-text review were conducted in Covidence by two reviewers, with disagreements resolved by the first author. Twelve studies met the inclusion criteria. Data were extracted into a structured evidence table, and findings were synthesised. Results: Across studies, cluttering emerged as a developmental motor–cognitive integration disorder. Speech motor systems, linguistic formulation and executive control showed difficulty aligning under real-world communicative demands, leading to timing instability, articulatory blurring and reduced intelligibility. Symptoms were strongly influenced by task complexity, with spontaneous and extended discourse eliciting the most pronounced breakdowns. Conclusions: Cluttering reflects a developmental vulnerability in coordinating speech motor, linguistic and executive processes. Understanding cluttering in this way challenges narrow rate-based definitions and supports more nuanced approaches to assessment and intervention. Significant evidence gaps remain, particularly in longitudinal, mechanistic, multilingual and ecologically valid research. This developmental motor–cognitive framework strengthens the conceptual foundations of cluttering and clarifies its relevance to children’s motor development. Full article

Motor disorders are increasingly recognized as a significant complication of chronic kidney disease (CKD), yet they remain underdiagnosed, undertreated, and often overlooked in clinical practice. Patients with CKD experience a broad spectrum of motor disturbances, including restless legs syndrome, myoclonus, flapping tremor, periodic limb movements in sleep, Parkinsonism, and peripheral neuropathy. These disorders arise from complex and often overlapping mechanisms such as uremic neurotoxicity, vascular injury, electrolyte and hormonal imbalances, or inflammatory processes, reflecting the systemic impact of impaired renal function on the central and peripheral nervous systems. The presence of motor disorders in CKD is associated with substantial clinical consequences for quality of life, contributing to impaired mobility, persistent insomnia, daytime fatigue, higher fall risk, and diminished independence. Moreover, these disturbances have been linked to increased cardiovascular morbidity and mortality, further exacerbating the already high burden of disease in this population. Current management approaches focus on optimizing kidney function through dialysis or transplantation, pharmacological therapies such as dopaminergic agents, gabapentinoids, and iron supplementation, as well as non-pharmacological interventions including structured exercise programs and sleep hygiene measures. Despite these strategies, robust evidence on long-term outcomes, comparative effectiveness, and optimal treatment algorithms remains limited. Greater recognition of the clinical impact of motor disorders in CKD, combined with targeted research efforts, is urgently needed to improve patient-centered outcomes and guide evidence-based care. Full article