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Search Results (1,164)

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Keywords = motoric deficit

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12 pages, 3003 KB  
Article
Efficacy of Forward and Reverse Suturing Techniques in Enhancing Neural Regeneration and Motor Function Recovery Following Facial Nerve Axotomy
by Jae Min Lee, Yeon Ju Oh, Sung Soo Kim, Youn-Jung Kim and Seung Geun Yeo
J. Clin. Med. 2026, 15(1), 96; https://doi.org/10.3390/jcm15010096 (registering DOI) - 23 Dec 2025
Abstract
Background/Objectives: Facial nerve injury from conditions such as Bell’s palsy, trauma, surgery, and infection leads to facial asymmetry and motor deficits. Axotomy models reproduce peripheral nerve disruption and consequent motor impairment. To compare the effects of forward versus reverse autologous nerve suturing [...] Read more.
Background/Objectives: Facial nerve injury from conditions such as Bell’s palsy, trauma, surgery, and infection leads to facial asymmetry and motor deficits. Axotomy models reproduce peripheral nerve disruption and consequent motor impairment. To compare the effects of forward versus reverse autologous nerve suturing on neural regeneration and motor recovery within the facial nucleus after axotomy. Methods: In rats subjected to facial nerve axotomy, motor recovery was assessed at 8 weeks using whisker movement and blink reflex tests. Immunohistochemistry quantified choline acetyltransferase (ChAT), sirtuin 1 (SIRT1), and Iba-1 as indices of cholinergic function, cellular stress/inflammation modulation, and microglial activation in the facial nucleus. Results: Axotomy significantly reduced whisker and blink scores compared with sham. Both forward and reverse suturing significantly improved these behavioral outcomes versus axotomy. Within the facial nucleus, axotomy decreased ChAT- and SIRT1-positive cells and increased Iba-1 expression, while both suturing techniques increased ChAT and SIRT1 and reduced Iba-1. These changes suggest enhanced cholinergic function, mitigation of stress/inflammatory responses, and attenuation of microglial activation following repair. Conclusions: Forward and reverse suturing were each associated with improved motor function and favorable molecular and cellular changes in the facial nucleus after facial nerve axotomy. These findings support the utility of surgical repair irrespective of graft orientation and highlight involvement of key pathways—cholinergic signaling, SIRT1-related regulation, and microglial activity—in nerve restoration. This work extends our previous study, which focused on peripheral nerve regeneration after forward and reverse suturing, by elucidating how graft orientation affects central facial nucleus responses. By integrating behavioral outcomes with ChAT, Iba-1, and SIRT1 expression, the present study provides novel insight into the central mechanisms underlying motor recovery after facial nerve repair and helps explain why comparable functional outcomes are achieved regardless of graft polarity. Full article
(This article belongs to the Section Otolaryngology)
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20 pages, 825 KB  
Review
Zinc Oxide Nanoparticle-Induced Neurotoxicity: Underlying Molecular Mechanisms and Future Perspectives
by Chun Chen, Xingyao Pei, Yonger Yu, Chang Gao, Jinran Wang, Rongyao Zhu, Shuxuan Liu, Shusheng Tang and Daowen Li
Toxics 2026, 14(1), 11; https://doi.org/10.3390/toxics14010011 - 20 Dec 2025
Abstract
The expanding application of zinc oxide nanoparticles (ZnO NPs) in consumer products, medicine, and the food industry has raised significant concerns regarding their potential neurotoxicity. This review synthesizes current understanding of the pathways by which ZnO NPs gain access to the central nervous [...] Read more.
The expanding application of zinc oxide nanoparticles (ZnO NPs) in consumer products, medicine, and the food industry has raised significant concerns regarding their potential neurotoxicity. This review synthesizes current understanding of the pathways by which ZnO NPs gain access to the central nervous system (CNS), their resulting neurotoxic effects, and the underlying molecular mechanisms. These nanoparticles primarily breach the CNS via translocation across the blood–brain barrier, axonal transport along sensory nerves, and disruption of the microbiota–gut–brain axis. Upon entry, ZnO NPs induce behavioral deficits, including impaired learning, memory, and motor function, alongside pathological brain damage. The neurotoxicity is driven by a multi-faceted mechanism involving mitochondrial dysfunction, oxidative stress, energy depletion, and neuroinflammation, often triggered by the release of Zn2+ ions. Furthermore, ZnO NPs can activate diverse cell death pathways, including apoptosis, ferroptosis, and pyroptosis. Critically, their neurotoxic potential is intrinsically linked to their physicochemical properties, such as size and shape. Emerging evidence also suggests that ZnO NP exposure may promote the aggregation of pathological proteins like Tau, thereby potentially increasing the risk for neurodegenerative diseases. Finally, we discuss potential mitigation strategies, such as surface modification and intervention with natural compounds. This review underscores the need for a refined risk assessment of ZnO NPs to ensure their safe deployment. Full article
22 pages, 3476 KB  
Article
Longitudinal Changes in Brain Network Metrics and Their Correlations with Spinal Cord Diffusion Tensor Imaging Parameters Following Spinal Cord Injury and Regenerative Therapy
by Ting Feng, Can Zhao, Wen-Nan Su, Yi-Meng Gao, Yuan-Yuan Wu, Wen Zhao, Jia-Sheng Rao, Zhao-Yang Yang and Xiao-Guang Li
Biomedicines 2025, 13(12), 3124; https://doi.org/10.3390/biomedicines13123124 - 18 Dec 2025
Viewed by 226
Abstract
Objectives: Spinal cord injury (SCI) disrupts the microstructure of the spinal cord, triggers reorganization of the brain network, and causes motor deficits. However, the temporal dynamics and interrelationships of these alterations remain unclear. Methods: Eight monkeys underwent spinal cord hemisection and were randomly [...] Read more.
Objectives: Spinal cord injury (SCI) disrupts the microstructure of the spinal cord, triggers reorganization of the brain network, and causes motor deficits. However, the temporal dynamics and interrelationships of these alterations remain unclear. Methods: Eight monkeys underwent spinal cord hemisection and were randomly assigned to either the SCI-only group or the treatment group that received neurotrophin-3-chitosan implants. Longitudinal brain structural/resting-state magnetic resonance imaging and spinal cord diffusion tensor imaging (DTI) were conducted. Concurrently, hindlimb motor function was assessed. The brain network topology was characterized through graph theory. The generalized additive mixed model (GAMM) was employed to analyze the longitudinal trajectories of network metrics, while the linear mixed-effects model (LMM) was used to evaluate the moderating effect of treatment on correlations between network metrics and motor/DTI parameters. Results: The SCI-only group exhibited sustained functional network segregation, aberrant structural topology, and lower fractional anisotropy (FA). These findings collectively reflect chronic maladaptive plasticity. In the treatment group, the therapy not only enhanced white matter integrity, reflected by increased FA values, but also reduced the clustering coefficient (Cp) in brain structural network, indicating a shift away from maladaptive segregation. Critically, the LMMs further revealed that treatment moderated the pathological correlations between global efficiency (Eg), local efficiency, Cp, and locomotor parameters. Moreover, spinal FA exerted a significant main effect on Eg of brain functional networks. Conclusions: These findings suggest that treatment-induced brain reorganization underlies motor function following SCI, and progressive brain reorganization correlates with changes in spinal cord microstructure, revealing a systems-level mechanism of neural repair. Full article
(This article belongs to the Special Issue Modern Applications of Advanced Imaging to Neurological Disease)
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11 pages, 951 KB  
Article
Sensor-Based Assessment of Post-Stroke Shoulder Pain and Balance
by Eda Salgut, Gökhan Özkoçak and Arzu Dinç Yavaş
Sensors 2025, 25(24), 7665; https://doi.org/10.3390/s25247665 - 18 Dec 2025
Viewed by 203
Abstract
Background/Objectives: Hemiplegic shoulder pain (HSP) is a frequent post-stroke complication affecting 30–65% of survivors, contributing to motor dysfunction and reduced quality of life. Balance impairment is another major concern that increases fall risk. This study aimed to examine the associations between HSP, [...] Read more.
Background/Objectives: Hemiplegic shoulder pain (HSP) is a frequent post-stroke complication affecting 30–65% of survivors, contributing to motor dysfunction and reduced quality of life. Balance impairment is another major concern that increases fall risk. This study aimed to examine the associations between HSP, shoulder range-of-motion (ROM) limitations and balance performance using both clinical and sensor-based evaluations. Methods: In this cross-sectional study, 108 stroke survivors (54 with HSP, 54 without) were assessed. Pain intensity was evaluated using the Visual Analog Scale (VAS), balance with the Berg Balance Scale (BBS), and shoulder mobility and postural sway with the validated Euleria Lab IMU-based system integrated with a force platform. Between-group differences were analyzed using the Mann–Whitney U test, and correlations between pain, ROM, balance, and fall-risk indices were determined via Spearman coefficients. Results: Participants with HSP had significantly lower BBS scores (20.96 ± 8.71) than those without HSP (34.58 ± 11.71; p < 0.001). VAS activity scores were negatively correlated with BBS (r = −0.196, p = 0.043) and positively correlated with postural sway and fall-risk parameters, particularly under eyes-closed conditions. Shoulder ROM limitations were linked to poorer balance, and both static and dynamic fall-risk indices were strongly correlated with pain severity (r = 0.676 and r = 0.657; p < 0.001). Conclusions: HSP was associated with impaired balance and elevated fall risk in stroke survivors. The combination of clinical scales and wearable sensor-based measurements provides a comprehensive understanding of postural control deficits. These findings emphasize the need for rehabilitation strategies targeting pain reduction, shoulder mobility, and balance to support functional recovery. Full article
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15 pages, 1052 KB  
Systematic Review
Effects of Transcranial Neuromodulation on Rehabilitation Outcomes After Anterior Cruciate Ligament Injury: A Systematic Review of Randomized Controlled Trials
by Juan Vicente-Mampel, Mariola Belda-Antolí, Eloy Jaenada-Carrilero, Andrés Pascual-Leone, Luís Baraja-Vegas, Nicolás Pascual-Leone, Javier Ferrer-Torregrosa, Francisco J. Falaguera-Vera, Álvaro Pascual-Leone and José María Tormos-Muñoz
Biomedicines 2025, 13(12), 3068; https://doi.org/10.3390/biomedicines13123068 - 12 Dec 2025
Viewed by 266
Abstract
Background/Objectives: Anterior cruciate ligament (ACL) injuries frequently lead to long-term quadriceps impairments despite surgical repair. There is growing evidence that these deficits are caused in part by alterations in the central nervous system. Thus, transcranial neuromodulation (TNM) could be valuable in ACL [...] Read more.
Background/Objectives: Anterior cruciate ligament (ACL) injuries frequently lead to long-term quadriceps impairments despite surgical repair. There is growing evidence that these deficits are caused in part by alterations in the central nervous system. Thus, transcranial neuromodulation (TNM) could be valuable in ACL rehabilitation. To systematically review randomized controlled trials (RCTs) assessing the effects of TNM on neurophysiological, functional, and safety outcomes in patients with ACL injury or reconstruction. Methods: We conducted searches on PubMed, Scopus, Web of Science, and Cochrane. We considered all original studies evaluating TNM, including transcranial current stimulation (tCS) and transcranial magnetic stimulation (TMS), in patients with ACL reconstruction or injury. Measures of corticospinal excitability, safety, balance, and muscle strength were assessed. We employed the Cochrane RoB 2 method to assess the risk of bias. Results: Seven studies comprising 129 participants (64 TNM, 65 controls) were included. Most studies applied transcranial direct current stimulation (tDCS) over the primary motor cortex contralateral to the ACL injury in conjunction with physical rehabilitation. Single-session protocols demonstrated minimal effects, whereas repeated sessions resulted in improvements in corticospinal excitability, quadriceps strength, and balance. No serious adverse events were reported; minor effects included transient headache or scalp tingling. The risk of bias was assessed as low to moderate across the studies. Conclusions: TNM appears to be safe and may enhance functional recovery in individuals with ACL injuries when administered in multiple sessions alongside standard rehabilitation. Further high-quality trials are necessary to determine optimal protocols and long-term outcomes. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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11 pages, 239 KB  
Article
The Relationship Between Neurocognitive Function and Concussion in Women Professional Football Players: A Cross-Sectional Study
by Freja Fredrika Lähteenmäki, Steve den Hollander, Dina Christa Janse van Rensburg, Tuomas Brinck, Gino Kerkhoffs and Vincent Gouttebarge
Sports 2025, 13(12), 448; https://doi.org/10.3390/sports13120448 - 11 Dec 2025
Viewed by 283
Abstract
Objective: To determine the neurocognitive functions of women professional football players and explore their potential connection to concussions. Methods: An observational cross-sectional study was conducted via electronic questionnaires. Neurocognitive function was assessed with the “CNS Vital Signs” testing tool. Results: In total, 68 [...] Read more.
Objective: To determine the neurocognitive functions of women professional football players and explore their potential connection to concussions. Methods: An observational cross-sectional study was conducted via electronic questionnaires. Neurocognitive function was assessed with the “CNS Vital Signs” testing tool. Results: In total, 68 participants performed the neurocognitive function testing. Compared with the reference population, players scored within the average range (≥90) for 11 of 12 neurocognitive domains. Motor speed was above average (SS = 111.7). Overall, no significant neurocognitive deficits were observed. Thirty-two participants (43%) reported one or more concussions, with defenders being most affected (50%). Among defenders, 64% (n = 16) have a history of one or multiple concussions. Players with a history of three concussions showed significant deficits in the simple attention domain. Conclusion: Professional women footballers did not show significant signs of neurocognitive function deficits. However, a history of three concussions was significantly associated with lower standard scores for the simple attention neurocognitive domain. Full article
25 pages, 1163 KB  
Review
Sexual Dimorphisms in Neurodevelopment May Affect TBI Recovery in Pediatric Patients
by Moira F. Taber, Franklin D. West and Erin E. Kaiser
Biomedicines 2025, 13(12), 3033; https://doi.org/10.3390/biomedicines13123033 - 10 Dec 2025
Viewed by 186
Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability, with broad heterogeneity in recovery outcomes particularly noted in pediatric patients. Children post-TBI are vulnerable to aberrant neurodevelopment, specifically in structural and functional neural networks as they correlate with cognitive, behavioral, [...] Read more.
Traumatic brain injury (TBI) is a leading cause of death and disability, with broad heterogeneity in recovery outcomes particularly noted in pediatric patients. Children post-TBI are vulnerable to aberrant neurodevelopment, specifically in structural and functional neural networks as they correlate with cognitive, behavioral, and motor function outcomes. Consideration for sex as a biological variable which innately influences neuroanatomy, neurodevelopment, and functional organization may elucidate risk factors for negative outcomes in pediatric TBI. For example, TBI damage in sexually dimorphic neural structures and networks may explain deficits in social cognition, working memory, as well as internalizing and externalizing behaviors, which differentially impact the quality of life in male versus female TBI patients. However, characterization of sex in conjunction with developmental patterns in normal and injured pediatric populations is limited due to small sample sizes, the low representation of females, a lack of longitudinal data, and the utilization of analyses that are not sensitive enough to detect subtle differences in TBI pathologies and recovery between the sexes. This review aims to analyze and synthesize the existing evidence regarding the influence of sex on the developmental trajectories of neuroanatomical structures, white and gray matter compartments, and the network disruptions that align with sex-specific functional recovery outcomes following pediatric TBI. The delineation of these sex influences will facilitate better precision-based medicine approaches to improve patient outcomes. Full article
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11 pages, 234 KB  
Article
Long-Term Results of a Propensity Score Analysis Comparing 5 × 5 Gy and 10 × 3 Gy of Radiotherapy Alone for Malignant Spinal Cord Compression
by Dirk Rades, Darejan Lomidze, Carlos Ferrer-Albiach, Antonio Jose Conde-Moreno, Barbara Segedin, Blaz Groselj, Raquel Ciérvide Jurio, Fernando López Campos, Charlotte Kristiansen, Kristopher Dennis and Jon Cacicedo
J. Clin. Med. 2025, 14(24), 8741; https://doi.org/10.3390/jcm14248741 - 10 Dec 2025
Viewed by 167
Abstract
Background/Objectives: For many patients with malignant spinal cord compression (MSCC) not suitable for surgery, irradiation alone is the preferred treatment. A dose-fractionation regimen of 10 × 3 Gy is common for this situation. Since most patients suffer from motor deficits and pain, the [...] Read more.
Background/Objectives: For many patients with malignant spinal cord compression (MSCC) not suitable for surgery, irradiation alone is the preferred treatment. A dose-fractionation regimen of 10 × 3 Gy is common for this situation. Since most patients suffer from motor deficits and pain, the number of radiotherapy sessions should be as low as possible. A secondary analysis of a phase 2 trial compared 5 × 5 Gy to a historical control group treated with 10 × 3 Gy. After 1:2 matching, 5  ×  5 Gy appeared similarly effective regarding local progression-free survival (LPFS) at 6 months, motor function, walking ability, and overall survival. Methods: This retrospective study investigated whether these findings are consistent in a larger cohort and after longer follow-up. Additional data were gathered for the phase 2 cohort, follow-up in the control group was not limited to 6 months, and the number of patients in the control group increased from 213 to 728. Results: After propensity-score matching, no significant differences were found regarding LPFS after 12 (p = 0.198), 18 (p = 0.139), and 24 (p = 0.117) months, effect on motor function (p = 0.393), walking ability (p = 0.079), 24-month local control (p = 0.655), and 24-month OS (p = 0.403). Conclusions: Given the limitations of this study, 5 × 5 Gy appears preferable to 10 × 3 Gy in selected patients receiving irradiation without upfront surgery. Clinicians should balance initial convenience for the patients and future limitations when re-irradiation in the same part of the spine is required. Full article
(This article belongs to the Special Issue Clinical Advances in Radiation Therapy for Cancers)
12 pages, 796 KB  
Systematic Review
Epidemiological, Diagnostic, and Clinical Features of Intracranial Cystic Echinococcosis: A Systematic Review
by Songul Meltem Can, Feza Irem Aldi, Muhammed Burak Sarikaya, Pelin Sari Serin and Nermin Sakru
Pathogens 2025, 14(12), 1264; https://doi.org/10.3390/pathogens14121264 - 10 Dec 2025
Viewed by 215
Abstract
Cystic Echinococcosis (CE) is a rare but serious parasitic disease caused by Echinococcus granulosus sensu lato, representing only 1–2% of all hydatid disease cases. Due to its nonspecific clinical presentation, its diagnosis and management pose significant challenges. This study aimed to provide [...] Read more.
Cystic Echinococcosis (CE) is a rare but serious parasitic disease caused by Echinococcus granulosus sensu lato, representing only 1–2% of all hydatid disease cases. Due to its nonspecific clinical presentation, its diagnosis and management pose significant challenges. This study aimed to provide a comprehensive overview of intracranial CE cases reported globally over the past 35 years, focusing on demographic characteristics, clinical presentation, diagnostic approaches, treatment modalities, and outcomes. Methods: A systematic review was conducted in accordance with PRISMA guidelines and was registered in PROSPERO (CRD 42024608624). Relevant studies published between 1990 and 2024 were identified from PubMed, Scopus, and Web of Science databases. Results: After screening and eligibility assessment, 392 studies involving 718 intracranial CE cases were included. The majority of patients were children (65%) and male (59.2%). The most frequent presenting symptoms were signs of increased intracranial pressure (79.4%), followed by motor deficits (37.9%) and visual disturbances (23.2%). Most cysts were located in the supratentorial region (88.9%), predominantly in the parietal lobe, and were solitary (88.4%). Surgical intervention was performed in 95.8% of cases, often combined with albendazole therapy. Complete recovery was observed in 85.5% of patients, while 8.7% died—primarily due to cyst rupture-related complications such as septicemia and anaphylaxis. Recurrence was reported in 26% of cases with follow-up. Conclusions: This review presents one of the most extensive analyses of intracranial CE to date. Despite being a rare manifestation, intracranial CE should be considered in the differential diagnosis of space-occupying brain lesions in endemic areas, particularly in paediatric patients. Full article
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13 pages, 815 KB  
Article
The Contribution of Paresis, Age, and the Effect of Short Training on Cognitive–Motor Dual-Task Interference After Stroke: A Pilot Study
by Judit Málly, Orsolya Karácsony, Bernadette Kálmán and Trevor W. Stone
Life 2025, 15(12), 1881; https://doi.org/10.3390/life15121881 - 9 Dec 2025
Viewed by 249
Abstract
Simultaneously performing cognitive and motor tasks after a stroke interfered with each other. Considering the competing deficits of cognition and motor paresis, we aimed here to assess the overall functional impairments of patients after stroke injury. A range of dual-task (DT) assessments was [...] Read more.
Simultaneously performing cognitive and motor tasks after a stroke interfered with each other. Considering the competing deficits of cognition and motor paresis, we aimed here to assess the overall functional impairments of patients after stroke injury. A range of dual-task (DT) assessments was made on 63 post-stroke patients (PS) and 49 healthy age-matched controls. Patients with paresis (P) and without paresis (NP) were compared with controls before and after DT training. Differences between the NP patients and controls confirmed the cognitive decline, while the comparison between the NP and P patients strengthened the motor damage in P patients. The elderly patients performed worse. According to the ArtANOVA analysis, age was more important than paresis in DT performance. Short-term training modified the test results, especially in P patients. In conclusion, paresis and older age significantly worsen the outcomes of the cognitive dual-task tests. The age-dependent results may reflect cognitive decline, especially in NP patients. Consequently, the dual-task test results may represent global cognitive deterioration after stroke. Short-term dual-task training improves dual-task performance, especially in the P groups. Full article
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15 pages, 2315 KB  
Review
Degenerative Cervical Myelopathy Diagnosis and Its Differentiation from Neurological Mimics, MS and ALS: A Literature Review
by Sydney Klumb, Lauren Haley, Chase Hathaway, Jonathan Irby, Johnny Cheng and Jacob Rumley
J. Clin. Med. 2025, 14(24), 8711; https://doi.org/10.3390/jcm14248711 - 9 Dec 2025
Viewed by 510
Abstract
Multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and degenerative cervical myelopathy (DCM) share features that may confound diagnosis. DCM is caused by degenerative changes in the cervical spine leading to spinal cord compression and injury, resulting in significant disability. Misdiagnosis of DCM for [...] Read more.
Multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and degenerative cervical myelopathy (DCM) share features that may confound diagnosis. DCM is caused by degenerative changes in the cervical spine leading to spinal cord compression and injury, resulting in significant disability. Misdiagnosis of DCM for a similar neurological condition can lead to further spinal cord damage from delayed surgical treatment. Here we review the diagnostic criteria, clinical signs and symptoms, and imaging typical for DCM, and two of its clinical mimics, MS and ALS. Shared motor symptoms of all three conditions can make diagnosis difficult, especially early in disease course. Noteworthy differences include neck and shoulder pain in DCM, visual disturbances in MS, and bulbar symptoms and the absence of sensory deficits in ALS. In DCM and MS, MRI is used to support the diagnosis, with specific findings on MRI that differentiate DCM versus MS. In ALS, MRI is used to rule out differential diagnoses. Applying the diagnostic criteria for MS and ALS, as well as understanding the typical presentation and MRI findings of DCM, is crucial. Through discussion of these conditions, this review aims to help limit misdiagnosis rates, allowing for early management, which can improve long-term patient outcomes. Full article
(This article belongs to the Section Clinical Neurology)
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14 pages, 3314 KB  
Review
Immunotherapy and Radiation for Clinical Perineural Invasion in Cutaneous Squamous Cell Carcinoma
by Renee A. Morecroft, Jordan S. Phillipps, Lang Gou, Alok A. Bhatt, Sungjune Kim, Homan Mohammadi, Roxana S. Dronca, Bently Doonan, Ruqin Chen, Yujie Zhao, Hye Seon Kang, Shenduo Li, Jeffrey R. Janus, Phillip Pirgousis, Samip Patel, Oluwafunmilola T. Okuyemi, Elisha M. Singer, Leila M. Tolaymat, Ashley Wysong, Catherine A. Degesys, Naiara Barbosa and Adam L. Holtzmanadd Show full author list remove Hide full author list
Cancers 2025, 17(24), 3921; https://doi.org/10.3390/cancers17243921 - 8 Dec 2025
Viewed by 279
Abstract
Localized cutaneous squamous cell carcinoma (cSCC) has a favorable prognosis, unlike advanced disease, especially with clinical perineural invasion (PNI), which poses substantial management challenges due to aggressivity and higher recurrence, metastasis, and mortality risks. PNI, a high-risk staging feature, has worse outcomes, particularly [...] Read more.
Localized cutaneous squamous cell carcinoma (cSCC) has a favorable prognosis, unlike advanced disease, especially with clinical perineural invasion (PNI), which poses substantial management challenges due to aggressivity and higher recurrence, metastasis, and mortality risks. PNI, a high-risk staging feature, has worse outcomes, particularly when clinically evident rather than incidental. Clinical PNI (cPNI) is evident by clinical symptoms (such as pain, paresthesia, or motor deficits) or radiologic findings, whereas incidental PNI (iPNI) is identified only histologically without associated symptoms or radiologic evidence. PNI remains a novel area with varying practice patterns across institutions. Improving risk stratification and tailoring multidisciplinary approaches are critical for optimizing outcomes. Our review outlines clinical practice patterns at our institution, providing insights into managing cSCC with PNI, focusing on diagnosis, imaging, staging, and emerging immunotherapies. A structured search was conducted using the terms “perineural invasion,” “cutaneous squamous cell carcinoma,” and “immunotherapy.” cPNI has a poor prognosis and requires nuanced clinical decision-making. Surgery and radiation remain central to management. Adjuvant therapy offers substantial survival benefit in cSCC with PNI, with improved disease-free and overall survival compared with surgery alone, supporting its use in appropriately selected high-risk patients. Traditional systemic therapies, including cisplatin and cetuximab, remain foundational but have shown only moderate response rates and limited durability in advanced or neurotropic cSCC. In contrast, immunotherapy—now preferred for advanced or unresectable cases—has transformed management, with programmed cell death protein-1 (PD-1) inhibitors showing promising results (up to 69% response rate) and disease stabilization. Neoadjuvant immunotherapy may enable tumor downstaging, improve radiation planning, and reduce surgical morbidity. Imaging for squamous cell carcinoma (SCC) with PNI aids staging and surveillance, but symptoms remain key for detecting recurrence. Our multidisciplinary approach emphasizes personalized care. Larger trials are needed to define the optimal role and sequencing of immunotherapy in this high-risk patient population. Full article
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13 pages, 916 KB  
Case Report
Balance, Gait Kinematics, and Fear of Falling After a Four-Month Targeted Training Program in a Patient with Cervical Dystonia: A Case Report
by Oscar Crisafulli, Marta Sarrocco, Matteo Fortunati, Marco Serra, Venere Quintiero and Giuseppe D’Antona
Int. J. Environ. Res. Public Health 2025, 22(12), 1831; https://doi.org/10.3390/ijerph22121831 - 6 Dec 2025
Viewed by 405
Abstract
In cervical dystonia (CD), balance and gait impairments can compromise daily activities and negatively affect quality of life. However, interventions addressing these deficits remain poorly investigated. A 54-year-old woman with CD, presenting balance and gait difficulties that interfered with work-related motor tasks, underwent [...] Read more.
In cervical dystonia (CD), balance and gait impairments can compromise daily activities and negatively affect quality of life. However, interventions addressing these deficits remain poorly investigated. A 54-year-old woman with CD, presenting balance and gait difficulties that interfered with work-related motor tasks, underwent a four-month training program. Sessions (40 min, three times per week) combined lower-limb strengthening, proprioceptive and balance exercises, and integrated motor–cognitive tasks. Pre- and post-intervention assessments included gait speed (GS), stride length (SL), and stance time (ST) under usual (UW), fast (FW), and dual-task (DT) walking conditions, measured with an inertial sensor (BTS G-Walk). DT cost was calculated for GS and SL. Balance was evaluated with the Mini-BEST and Four-Square Step Test (FSST), while fear of falling was measured with the Falls Efficacy Scale-International (FES-I). Of note, both assessment sessions were conducted in the absence of botulinum toxin effects, whereas the training was performed, at least in part, under its influence. After training, increase were observed in GS and SL, with reductions in ST across all gait conditions. DT cost decreased for both GS and SL. Balance performance increased, and fear of falling was reduced. Importantly, the patient reported a marked improvement in work-related performance. This case suggests that a specific training program may effectively ameliorate balance and gait in CD, with positive effects on functional mobility. Further studies on larger samples are warranted to confirm efficacy. Full article
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11 pages, 1335 KB  
Article
Combined Histological and Proteomic Analysis Reveals Muscle Denervation in KMT5B-Related Neurodevelopmental Disorder: A Case Report
by Ozge Aksel Kilicarslan, Andrea Gangfuß, Heike Kölbel, David Muhmann, Kiran Polavarapu, Rachel Thompson, Linda-Isabell Schmitt, Lola Lessard, Lei Chen, Astrid Eisenkölbl, Ulrike Schara-Schmidt, Andreas Hentschel, Hanns Lochmüller and Andreas Roos
J. Clin. Med. 2025, 14(24), 8636; https://doi.org/10.3390/jcm14248636 - 5 Dec 2025
Viewed by 241
Abstract
Background: Patients with neurodevelopmental and neuromuscular disorders often show overlapping clinical phenotypes. Pathogenic variants in KMT5B, a histone lysine methyltransferase, have been linked to neurodevelopmental disorders, yet their effects on human skeletal muscle remain unexplored. We report on a patient with [...] Read more.
Background: Patients with neurodevelopmental and neuromuscular disorders often show overlapping clinical phenotypes. Pathogenic variants in KMT5B, a histone lysine methyltransferase, have been linked to neurodevelopmental disorders, yet their effects on human skeletal muscle remain unexplored. We report on a patient with KMT5B-linked disease who presented to a neuromuscular specialty clinic with significant involvement of skeletal muscle, where a multi-omics approach established the genetic diagnosis and revealed neuromuscular findings relevant for diagnosis, care and rehabilitation. Methods: Whole-exome sequencing was performed from blood and data was analyzed using the RD-Connect Genome Phenome Analysis Platform. Histological analysis and proteomic profiling were performed on muscle tissue. Results: Whole-exome sequencing revealed a pathogenic heterozygous variant (c.554_557del, p.Tyr185Cysfs*27) in KMT5B. Histological examination revealed fiber-type grouping, angular fibers, increased fast-twitch fiber proportion, and lipid droplet accumulation, indicative of muscle denervation. Proteomic profiling identified 77 dysregulated proteins, including upregulation of sarcomeric proteins, mitochondrial and glycolytic enzymes, acute-phase and complement factors, and extracellular matrix components, reflecting structural remodeling, metabolic adaptation, and inflammatory activation. These findings align with the role types observed in Kmt5b mouse models, supporting a role of KMT5B in neuromuscular function. Conclusions: We present the first combined histological and proteomic analysis of quadriceps muscle from a patient carrying a pathogenic KMT5B variant with a neuromuscular phenotype. The convergence of histological and proteomic alterations suggests that KMT5B haploinsufficiency may be associated with fiber-type shifts, denervation, and metabolic stress in human skeletal muscle. Understanding these processes provides mechanistic insight into motor deficits and informs targeted therapeutic strategies, including physiotherapeutic interventions, and early compensatory measures. Full article
(This article belongs to the Special Issue Clinical Care and Rehabilitation for Neuromuscular Diseases)
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13 pages, 294 KB  
Article
Gait and Dual-Task Performance in Older Adults with Suspected Cognitive Impairment: Effects of an 8-Week Exercise Program
by João Galrinho, Marco Batista, Marta Gonçalves-Montera, Orlando Fernandes and Ana Rita Matias
Healthcare 2025, 13(24), 3190; https://doi.org/10.3390/healthcare13243190 - 5 Dec 2025
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Abstract
Background/Objectives: Gait performance in aging relies heavily on cognitive resources, yet the extent to which short-term interventions can mitigate dual-task costs in institutionalized populations remains understudied. This study aimed to compare single and dual-task gait performance between older adults with and without suspected [...] Read more.
Background/Objectives: Gait performance in aging relies heavily on cognitive resources, yet the extent to which short-term interventions can mitigate dual-task costs in institutionalized populations remains understudied. This study aimed to compare single and dual-task gait performance between older adults with and without suspected cognitive impairment and to evaluate the effects of an 8-week multicomponent exercise program on functional mobility. Methods: Institutionalized older adults (n = 42) were stratified into two groups: suspected cognitive impairment (n = 26) and no suspected impairment (n = 16), based on MMSE and Clock Drawing Test screening. Participants performed the Timed Up and Go (TUG) and Dual-Task TUG (TUG-DT) at baseline and post-intervention. Results: At baseline, the suspected impairment group exhibited significantly poorer performance on both tests (p < 0.001) compared to the non-impaired group. Following the 8-week intervention, the suspected impairment group demonstrated large, significant improvements in both TUG (r = −0.73) and TUG-DT (r = −0.59), whereas the non-impaired group remained stable. Notably, while the single-task TUG showed the greatest responsiveness to the exercise program, the TUG-DT continued to reveal a significant cognitive-motor load. Conclusions: Multicomponent exercise effectively enhances functional mobility in cognitively vulnerable older adults, reversing declines in both single and dual-task conditions. Significance: These findings support the implementation of dual-task screening to unmask latent functional deficits and validate the use of accessible, short-term multicomponent exercise programs as a vital strategy to preserve autonomy in institutionalized older adults. Full article
(This article belongs to the Special Issue Cutting-Edge Approaches in Neurological Disease Treatment)
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