Paratonia, a movement disorder characterized by involuntary muscle resistance, affects nearly all people with advanced dementia and contributes to caregiver burden, hygiene complications, pressure injuries, and pain. With Alzheimer's disease and related dementias affecting 7.2 million Americans and projected to reach nearly 14 million by 2060, the clinical impact of paratonia will expand proportionally. Because the involuntary muscle resistance of paratonia is frequently misinterpreted as deliberate noncompliance, individuals may receive inappropriate pharmacologic management rather than targeted treatment of the underlying movement disorder. No treatments are currently approved specifically for paratonia-induced muscle postures. Passive motion therapy, which the Centers for Medicare & Medicaid Services quality standards promote for contracture prevention in nursing homes, showed no benefit for paratonia in a randomized controlled trial of individuals with advanced dementia. Furthermore, passive movement therapy may paradoxically reinforce abnormal motor patterns by triggering increased involuntary resistance, the defining feature of paratonia. Botulinum toxin A, in therapeutic use since 1989, with Food and Drug Administration approval, is an established treatment for post-stroke spasticity and cervical dystonia. These conditions, like paratonia, arise from distinct central nervous system pathologies but share a peripheral manifestation of involuntary sustained muscle contraction. Preliminary clinical evidence suggests potential safety and efficacy for paratonia-induced muscle postures. Despite the therapeutic rationale and preliminary evidence for safety and efficacy, pharmaceutical companies have not pursued regulatory approval for the paratonia indication. This article examines barriers to clinical development, including scientific uncertainties, knowledge gaps, infrastructure limitations, therapeutic nihilism, policy barriers, and pharmaceutical industry considerations. We propose coordinated stakeholder action across research, education, policy, and regulatory domains to establish pathways toward further research and, if warranted, clinical implementation.

Paratonia is a movement disorder characterized by involuntary muscle stiffening that affects nearly all individuals with advanced dementia, yet it remains poorly recognized in routine clinical practice. Often misinterpreted as intentional resistance to care, untreated paratonia may progress to muscle contractures with secondary consequences, including pressure injuries, pain, and difficulty with caregiving. This clinical review provides clinicians with practical guidance in recognizing paratonia as a reflexive phenomenon rather than a behavioral disturbance. Three illustrative cases demonstrate presentations across care settings and clinical presentations. The article addresses bedside assessment, medications to avoid, indications for specialist referral, and both pharmacologic and nonpharmacologic management options.

Huntington's disease (HD) is an inherited hyperkinetic movement disorder allied with chorea, cognitive impairment, and psychological disorders. Nerolidol (NRD) is a natural sesquiterpene alcohol obtained from many plants that has been shown to display neuroprotective properties. The current study focused on investigating the mechanism behind the neuroprotective role of NRD against 3-nitropropionic acid (3-NP)-induced neurotoxicity in experimental animals. Initial prediction was carried out through computational modeling (in silico), followed by a series of in vitro and in vivo experiments utilizing batteries of behavioral and molecular tests. Molecular docking was performed using Schrödinger (Maestro 2.0) to further explore NRD's neuroprotective capacity against 3-NP-induced neurotoxicity in SH-SY5Y cell lines and rats. For the in vivo study, 24 adult Wistar rats were randomly divided into four different groups, while NRD (50 and 100 mg/kg) was chosen to study their neuroprotective impact against HD-like symptoms utilizing different behavioral, biochemical, and histopathological parameters. In silico studies demonstrated that NRD has a high binding affinity for active sites of targeted enzymes, while in vitro data showed that NRD can counteract the neurotoxic effects of 3-NP in SH-SY5Y cells. NRD therapy (50 and 100 mg/kg) significantly improved motor activity, levels of malondialdehyde and glutathione, and histopathological changes. The findings revealed that NRD offers antioxidant and neuroprotective effects against 3-NP-induced neurotoxicity. The observed results indicated that NRD may exert its effects by activating the Nrf2 and heme oxygenase-1 pathways. Thus, it is suggested that it may be employed as an alternative treatment to fight against neurotoxicity.

Minimally invasive neurosurgical techniques have emerged as a transformative paradigm, offering alternatives to conventional open approaches. The demand for safer, less invasive procedures accelerated the development of laser interstitial thermal therapy (LITT), focused ultrasound (FUS), and radiofrequency ablation (RFA), each employing a distinct mechanism with unique clinical implications. The objective was to critically evaluate and contextualize LITT, FUS, and RFA with emphasis on their comparative efficacy, safety, and roles as competing or complementary technologies in minimally invasive neurosurgery. Literature published between 2005 and 2025 was identified through PubMed, Scopus, and Web of Science, using keywords "LITT," "FUS," "RFA," "minimally invasive neurosurgery," "epilepsy," "glioma," and "movement disorders." Eligible English studies included clinical trials, systematic reviews, meta-analyses, and large observational studies. The extracted data were synthesized narratively, focusing on clinical indications, efficacy, safety, and patient-centered outcomes. Evidence highlights the roles of LITT, FUS, and RFA across tumors, epilepsy, and movement disorders with differing efficacy and safety indications. LITT is most effective in gliomas and metastases, FUS shows its strongest evidence in movement disorders, whereas LITT and RFA via stereo-electroencephalography-guided thermocoagulation remain relevant in epilepsy. Reported safety outcomes include edema with LITT, skull heating with FUS, and hemorrhage with RFA. Patient-centered outcomes across modalities suggest shorter recovery periods, improved cosmesis and quality of life, and favorable cost-effectiveness. LITT, FUS, and RFA represent complementary rather than competitive modalities in minimally invasive neurosurgery. Advances in imaging, navigation, thermal technologies, and patient-centered approaches are likely to accelerate their integration into cohesive, multimodal neurosurgical strategies.

The regeneration of orodental and craniofacial tissues remains a primary clinical challenge owing to the requirement of harmonized integration of hard-soft tissues, immune modulation, neurogenesis, angiogenesis, and osteogenesis. Extracellular vesicles (EVs) are nanoparticles containing RNAs, metabolites, lipids, and proteins that have surfaced as vital paracrine regulators able to coordinate these intricate mechanisms without the intrinsic risks associated with cell transplantation. This review synthesizes extensive in vivo evidence and evolving clinical findings highlighting that EVs from immune cells, mesenchymal stem cells, dental stem cells, and engineered origins regulate periodontal and dental pulp regeneration, peri-implant osseointegration, temporomandibular joint disorders, root resorption, orthodontic tooth movement, and craniomaxillofacial bone repair. EVs function as context-based biological regulators: regenerative EVs enhance M2 (anti-inflammatory) macrophage polarization, neurogenesis, angiogenesis, and odonto-osteogenesis, while EVs from pathogenic, mechanically stressed, or inflamed cells can initiate inflammation, osteoclastogenesis, and tissue damage. EV long noncoding RNAs and microRNAs play a critical part in dictating reparative versus destructive outcomes by regulating the TGF-β/SMAD, PI3K/protein kinase B, NF-κB, and immune-metabolic cascades. Biomaterial-based delivery platforms and engineered EVs, such as surface-modified dental implants, scaffolds, and hydrogels, consistently improved local retention, efficacy, and multi-tissue repair. Crucially, human studies indicate clinically significant enhancements in periodontal and alveolar bone regeneration, emphasizing their translational promise. Nonetheless, clinical implementation is restricted by heterogeneity in EV origins, cargo variability, manufacturing methods, dosage, and delivery approaches, together with an incomplete comprehension of how to predict their bioactivity. Future advances will mandate Minimal Information for Studies of Extracellular Vesicles (MISEV)-guided optimization, functional release criteria, localized delivery systems, potency-driven classification, and scalable Good Manufacturing Practices production. Overall, current evidence positions EVs as cell-free, adaptable mediators with transformative potential for precision-guided craniofacial therapy and regenerative dentistry.

Cognitive impairment (CI) is a significant non-motor symptom of Parkinson's disease (PD), necessitating effective assessment tools to evaluate treatment efficacy. Minimal Clinically Important Difference (MCID) thresholds provide critical benchmarks for interpreting cognitive intervention outcomes. This study establishes MCID values for PD Cognitive Rating Scale (PD-CRS), Scales for Outcomes in PD-Cognition (SCOPA-COG), and Montreal Cognitive Assessment (MoCA) in PD-CI. A total of 110 patients with PD-CI were recruited; 105 (mean age 71.96 ± 2.40 years) completed the 12-week Dual-Task Training (DTT) program and were included in the final analyses. Cognitive function was assessed using PD-CRS, SCOPA-COG, and MoCA at baseline and post-intervention, with the Global Rating of Change (GRoC) questionnaire serving as an anchor. The MCID value was determined using anchor-based and distribution-based approaches. Receiver Operating Characteristic (ROC) analysis was employed to evaluate these thresholds. Significant improvements were observed across all cognitive measures post-intervention. The anchor-based MCID values were 7.70 points for PD-CRS, 3.11 points for SCOPA-COG, and 2.05 points for MoCA, respectively. Additionally, ROC curve analysis further determined that MCID cut-off points were > 3 points for the PD-CRS, > 2 points for the SCOPA-COG, and > 1 point for the MoCA. The distribution-based MCID values ranged from 1.48 to 4.10 points for PD-CRS, 1.37 to 5.95 points for SCOPA-COG, and 0.54 to 3.71 points for MoCA. This study established MCID thresholds for PD-CRS, SCOPA-COG, and MoCA in PD-CI, providing essential tools for clinicians and researchers to assess clinically meaningful changes after cognitive intervention.

Human social interactions rely on the ability to reflect on one's own and others' internal states and traits-a process known as mentalizing. Impaired or altered mentalizing is a hallmark of multiple psychiatric and neurodevelopmental conditions. Yet, replicable and easily testable brain markers of mentalizing have so far been lacking. Here, we apply an interpretable machine learning approach to multiple datasets (total n = 390) to train and validate fMRI brain signatures that predict i) mentalizing about the self, ii) mentalizing about another person, and iii) both types of mentalizing. Self-mentalizing and other-mentalizing classifiers had positive weights in anterior/medial and posterior/lateral brain areas, respectively, with accuracy rates of 82% and 77% for out-of-sample prediction. The classifier trained across both types of mentalizing showed 98% predictive accuracy and separated (mental) attributional from factual inferences. Classifier patterns revealed better self/other separation in healthy adults compared to individuals with schizophrenia and with increasing age in adolescence. Together, our findings reveal consistent and separable neural patterns subserving trait-based mentalizing about self and others-present at least from the age of adolescence and functionally altered in severe neuropsychiatric disorders. These mentalizing signatures hold promise as candidate neuromarkers of social-cognitive processes in different contexts and clinical conditions.