Search Results (154)

The genus Acmella has received growing attention for its pharmacological properties, including its potential applications in musculoskeletal disorders (MSDs). Plants in this genus, such as Spilanthes acmella, Blainvillea acmella, Acmella uliginosa, and Acmella oleracea contain various bioactive compounds which have demonstrated anti-inflammatory, analgesic, and anti-arthritic properties. This systematic review evaluates the clinical and preclinical evidence supporting the use of plants from Acmella genus for the treatment of MSD, such as arthritis, osteoporosis, muscle injuries, joint inflammation, and other related pathologies. The methodology used in this study involved a systematic literature review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, along with synthesis analysis and quality appraisal. The articles were retrieved from Scopus, Google Scholar, and PubMed databases. Eleven articles were further analyzed to determine the therapeutic potential of Acmella genus plants for musculoskeletal disorders. The plants included were Spilanthes acmella, Blainvillea acmella, Acmella uliginosa, and Acmella olerecia. The musculoskeletal disorders investigated were osteoporosis, osteoarthritis, and myopathies. The extracts from these plants were shown to decrease inflammation, enhance joint health, relieve pain, and stimulate osteogenic activity. These effects may be attributed to several active compounds found in these plants. The available evidence suggests that Spilanthes acmella and Blainvillea acmella have the potential to treat osteoporosis. Acmella oleracea and Acmella uliginosa have the potential to be used for the treatment of osteoarthritis, while Spilanthes acmella is used to treat myopathies. Further research is needed to establish the efficacy, optimal dosing, and safety of these plants. Full article

Background/Objectives: Achilles tendon pathologies, such as Achilles tendinitis, tendinosis, ruptures, and equinus contracture, cause pain and functional impairment. While surgical intervention is indicated in some cases, many patients are successfully managed with nonoperative treatment. The goal of this review was to evaluate the current evidence-based treatments for the nonoperative management of Achilles tendon disorders, focusing on indications and clinical outcomes. Methods: A scoping review of the literature was conducted from 2015 to 2025 from the PubMed database. Research published in the last ten years was included if it addressed nonoperative treatments for Achilles tendinopathy, acute ruptures, and/or equinus contracture. The outcome measures of interest included functional outcomes, re-rupture rates, and overall patient satisfaction. Results: Nonoperative management results in favorable outcomes for a wide range of Achilles tendon pathologies. Eccentric loading is supported for chronic tendinopathy, and functional rehabilitation programs with early mobilization have shown comparable outcomes to surgical repair for acute tendon ruptures. Combination therapy for the nonoperative management of equinus is favored. These therapies include stretching protocols, casting, and the botulinum toxin. Conclusions: The literature supports the notion that nonoperative management strategies for Achilles tendon pathologies provide symptom relief and functional improvement in patients. However, these treatment plans should be individualized and tailored to patient-specific goals. Full article

Background/Objectives: Alkaptonuria (AKU) is a rare genetic disorder characterized by elevated levels of circulating homogentisic acid (HGA), which accumulates in connective tissues. The musculoskeletal system is particularly susceptible to HGA deposition, often resulting in severe ochronotic osteoarthropathy, especially in the hips, shoulders, knees, and spine. However, little is known about the effects of AKU on skeletal muscle tissue. The study aimed to evaluate changes in lower limb muscles associated with AKU. Methods: This case report describes the treatment of ochronotic osteoarthropathy in the knee of a 73-year-old male patient. Muscle properties were assessed using the MyotonPRO device. The rectus femoris, vastus medialis, and patellar tendon were examined both preoperatively and three months postoperatively. Results: Following total knee arthroplasty (TKA) of the right knee, the patient demonstrated significant improvement in functional outcomes. The MyotonPRO assessment revealed measurable differences in muscle properties between the operated and non-operated limbs. Postoperative measurements indicated improvements in muscle tone, elasticity, and viscoelastic parameters in the treated limb. Conclusions: This case report supports the effectiveness of TKA as a treatment for ochronotic osteoarthropathy. Furthermore, it is the first study to use the MyotonPRO to assess muscle and tendon properties in a patient with AKU. These findings highlight the need for further research into the muscular effects of this rare metabolic disorder. Full article

Hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are increasingly recognized as complex, multisystem connective tissue disorders characterized by joint hypermobility and instability, chronic pain, autonomic dysfunction, immune dysregulation, and structural fragility. Despite their clinical impact and prevalence, the underlying pathophysiology remains poorly understood, and diagnosis is frequently delayed or missed altogether. Emerging research highlights the fascia as a central player in the pathogenesis of these conditions. This narrative review synthesizes current molecular, histological, and biomechanical findings to propose a fascia-centered framework for understanding hEDS and HSD. Evidence from transcriptomic and imaging studies reveals consistent abnormalities in fascial thickness, interfascial gliding, myofibroblast activation, tendon elongation, and tissue stiffness—findings that mirror the functional impairments reported in clinical populations. We explore fascia as a dynamic tissue network and consider how dysregulation in these processes may contribute to the widespread symptoms seen in hypermobility disorders. By reframing hEDS and HSD as disorders of pathological fascial remodeling, this review offers an integrated model that connects molecular mechanisms with clinical expression. It underscores the urgent need for multidisciplinary research to define diagnostic biomarkers, clarify therapeutic targets, and support the development of more effective, personalized interventions. Full article

Background and Clinical Significance: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder caused by mutations in the CYP27A1 gene, leading to impaired bile acid synthesis and systemic cholesterol deposition. The condition presents with a broad spectrum of symptoms affecting multiple organs and systems, including the eyes, central nervous system, tendons, and skeletal muscles. Due to its heterogeneous and often ambiguous clinical manifestations, CTX is frequently misdiagnosed or remains undiagnosed for years. Case Presentation: We report the case of a 37-year-old male who was admitted to our university hospital with a long-standing history of progressive muscle weakness in the arms and legs. His medical history revealed bilateral cataract surgery in childhood, cognitive decline, epilepsy, and bilateral round swellings of the Achilles tendons, suspected to be xanthomas. A clinical diagnosis of CTX was established, and sequencing analysis confirmed the presence of a homozygous pathogenic variant in the CYP27A1 gene. Despite the unavailability of chenodeoxycholic acid (CDCA) therapy in Bulgaria, symptomatic management was provided. Conclusions: This case underscores the diagnostic challenges associated with CTX and highlights the prolonged diagnostic journey faced by patients with rare neurogenetic disorders. It also emphasizes the need for increased awareness and early recognition of such conditions to improve patient outcomes. Full article

Extracellular vesicles (EVs) are membrane-bound structures released by cells carrying diverse biomolecules involved in intercellular communication. Small EVs are abundant in body fluids, playing a key role in cell signaling. Their natural occurrence and therapeutic potential, especially in the context of muscular disorders, make them a significant area of research. Sarcopenia, characterized by progressive muscle fiber loss, represents a pathological state in which EVs could offer therapeutic benefits, reducing morbidity and mortality. Recent studies have proposed an interplay between adipose tissue (AT) and skeletal muscle regarding sarcopenia pathology. AT dysregulation, as seen in obesity, contributes to skeletal muscle loss in a multifactorial way. While AT-derived stem cell (ATDSC) small EVs have been implicated in musculoskeletal homeostasis, their precise action in muscle regeneration remains incompletely understood. In this context, ATDSC-derived small EVs can stimulate skeletal muscle regeneration through improved proliferation and migration of muscle cells, enhancement of muscular perfusion, improvement of tendon and nerve regeneration, stimulation of angiogenesis, and promotion of myogenic differentiation. However, they can also increase skeletal muscle loss. Notably, this is the first comprehensive review to systematically examine the role of ATDSC-derived small EVs in sarcopenia. Full article

Background/Objectives: Hereditary spastic paraplegia type 52 (SPG52) is a rare, inherited neurodevelopmental condition passed down in an autosomal recessive pattern. In this report, we describe two siblings from Rwanda who exhibited classic signs of the disorder, including progressive lower-limb spasticity, significant delays in motor development, and exaggerated deep tendon reflexes. Methods: Genetic testing through Whole-Exome Sequencing (WES) reveals a rare homozygous splice-site variant (NM_001128126.3:c.295-3C>A) in the AP4S1 gene. Results: Despite the severity of symptoms, both children responded positively to treatment with muscle relaxants and regular physiotherapy. Notably, MRI scans of the brain and spine showed no structural abnormalities. Conclusions: By documenting this case, we add to the growing understanding of SPG52, particularly within under-represented Sub-Saharan African populations, and underscore the critical role of early genetic testing in guiding timely diagnosis and intervention. Full article

Platelet-rich plasma (PRP) therapy is increasingly recognized as a promising treatment for musculoskeletal disorders, including osteoarthritis (OA), tendinopathy, and muscle injuries. This narrative review synthesizes the current literature to evaluate the efficacy of PRP, with a focus on platelet dosing strategies, leukocyte composition, and preparation protocols. Evidence suggests that optimal therapeutic outcomes are achieved when platelet doses exceed 3.5 billion per injection, with cumulative doses of 10–12 billion across multiple treatments. In intra-articular applications, leukocyte-poor PRP (LP-PRP), characterized by reduced neutrophil content, demonstrates superior efficacy compared to leukocyte-rich PRP (LR-PRP). However, its effectiveness in tendon and muscle regeneration remains a subject of debate. Preliminary data suggest that the inclusion of peripheral blood mononuclear cells (PBMNCs) may enhance PRP efficacy, though robust clinical trials are required to confirm these findings. Furthermore, red blood cell contamination and pre-activation have been identified as detrimental to PRP effectiveness, highlighting the need for standardized preparation protocols. This review emphasizes the importance of tailoring PRP formulations to patient-specific factors and musculoskeletal conditions. Future research should focus on refining PRP preparation techniques, identifying optimal leukocyte compositions, and establishing standardized guidelines to enhance clinical outcomes. Full article

Introduction: Hereditary transthyretin amyloidosis (ATTRv) is a severe, multisystemic, autosomal dominant disease with variable penetrance caused by mutations in the TTR gene generating protein misfolding and accumulation of amyloid fibrils. The diagnosis is usually challenging because ATTRv may initially manifest with nonspecific multisystemic symptoms. Conversely, an early diagnosis is needed to start timely appropriate therapy. Hence, screening models have been proposed to improve ATTRv diagnosis. In this study, we propose a genetic screening model based on predefined “red flags” followed by “cascading screening” on first-degree relatives of patients who tested positive. Materials and methods: After obtaining written informed consent, genetic testing on salivary swabs was performed in individuals who met at least two major red flags for ATTRv (age > 65 years old, progressive sensory or sensorimotor neuropathy not responsive to steroids or immunomodulant therapies, recent and unexplained weight loss associated with gastrointestinal signs and symptoms, diagnosis of cardiac amyloidosis, bilateral or relapsing carpal tunnel syndrome, unexplained autonomic dysfunction) or one major flag and two minor flags (family history of neuropathy, ambulation disorders or cardiopathy, sudden cardiac death, a bedridden, wheelchaired patient without specific diagnosis excluding upper motor neuron diseases, infections, juvenile cardiac disease, ocular disorders, lumbar spine stenosis, biceps tendon rupture). Results: In the first screening phase, 29 suspected cases (individuals meeting at least two major red flags or one major red flag and two minor red flags) underwent genetic testing. One patient (3.5%) was diagnosed with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), carrying the Phe64Leu mutation. Then, cascade screening allowed for early recognition of two additional individuals (two pre-symptomatic carriers) among two first-degree relatives (100%). The identified patient was a 72-year-old man who had a family history of both cardiopathy, neuropathy, and a diagnosis of juvenile cardiac disease and progressive sensorimotor neuropathy unresponsive to steroids or immunomodulant therapies. Conclusions: ATTRv is a progressive and often fatal disease that should be promptly diagnosed and treated to stop progression and reduce mortality. Systematic screening for ATTRv yielded increased recognition of the disease in our neurological clinic. A focused approach for the screening of ATTRv-PN could lead to an earlier diagnosis and identification of asymptomatic carriers, enabling timely intervention through close clinical monitoring and early treatment initiation at symptom onset. Full article

Background: Distal intersection tenosynovitis (DIT) is a rare and recently described condition that affects the extensor pollicis longus (EPL), extensor carpi radialis brevis (ECRB), and longus (ECRL). Based on surgical observations, this study aimed to provide new insights into its physiopathology. Methods: This was a retrospective study of all patients who underwent surgery for DIT at our institution from 2015 to 2024. Five patients were included in the study. Results: Wrist joint issues clearly explained the occurrence of DIT in three cases. Tendon lesions were observed either on the extensor carpi radialis brevis or extensor pollicis longus. Conclusions: These additional data complement the existing literature, which primarily focuses on the anatomical mechanisms of DIT without fully explaining its causes. Our observations suggest that wrist joint or bone disorders may play a significant role in its occurrence. Lesions in different tendons suggest the involvement of distinct pathological mechanisms. Full article

Background and Objectives: Hemiplegic shoulder pain (HSP) is a common and disabling complication in stroke patients, yet its pathogenesis remains unclear. This longitudinal study aimed to investigate the clinical and ultrasound characteristics of HSP emerging within the first 72 h (T0) post-stroke, with follow-ups at one month (T1) and three months (T2). Materials and Methods: A total of 28 stroke patients with hemiparesis were assessed for HSP. Evaluations included pain severity during passive shoulder mobilization, passive and active range of motion, muscle strength, spasticity, and functional disability. Ultrasound examinations were conducted to assess tendon disorders, bursitis, effusion, glenohumeral subluxation, and adhesive capsulitis. Results: HSP prevalence increased over time, affecting 11% of patients at T0, 32% at T1, and 57% at T2. Higher baseline scores on the National Institutes of Health Stroke Scale (NIHSS), an established marker of stroke severity, were significantly associated with HSP (p < 0.05). At T2, patients with HSP exhibited greater impairment, including restricted passive and active range of movement, pronounced muscle weakness, and increased spasticity (p < 0.05). Ultrasound findings at T2 revealed that adhesive capsulitis and glenohumeral subluxation were significantly more frequent in HSP patients (p < 0.05). Adhesive capsulitis showed a significant increase from 0% at T0 to 21% at T2 (p = 0.031), while glenohumeral subluxation exhibited a non-significant rise from 4% to 21% (p = 0.063). Patients with these conditions experienced significantly greater pain progression (p < 0.001). Conclusions: These findings suggest that capsular pathology plays a key role in the development of HSP within the first three months after stroke. The results highlight the need for targeted interventions addressing glenohumeral subluxation and adhesive capsulitis to alleviate pain and improve rehabilitation outcomes. Full article

Tendons are connective tissues that join muscles and bones and are rich in glycosaminoglycans (GAGs). Decorin is a proteoglycan with one dermatan sulfate (DS) or chondroitin sulfate (CS) chain (a type of GAG) attached to its core protein and is involved in regulating the assembly of collagen fibrils in the tendon extracellular matrix (ECM). Calcium-activated nucleotidase 1 (CANT1), a nucleotidase that hydrolyzes uridine diphosphate into uridine monophosphate and phosphate, plays an important role in GAG synthesis in cartilage. In the present study, we performed detailed histological and biochemical analyses of the tendons from Cant1 knockout (Cant1^−/−) mice. No abnormalities were observed in the tendons on postnatal day 1 (P1); however, remarkable hypoplasia was observed on P30 and P180. The collagen fibrils were more angular and larger in the Cant1^−/− tendons than in the control (Ctrl) tendons. In the Cant1^−/− tendons, the DS/CS content was significantly reduced, and the DC/CS chains attached to the decorin core protein became shorter than those in the Ctrl tendons. No abnormalities were observed in the proliferation and differentiation of tendon fibroblasts (tenocytes) in the Cant1^−/− mice. These results strongly suggest that CANT1 dysfunction causes defective DS/CS synthesis, followed by impairment of decorin function, which regulates collagen fibrogenesis in the tendon ECM. Multiple joint dislocations are a clinical feature of Desbuquois dysplasia type 1 caused by human CANT1 mutations. The multiple joint dislocations associated with this genetic disorder may be attributed to tendon fragility resulting from CANT1 dysfunction. Full article

Some musculoskeletal disorders, including osteoarthritis; arthrosis; post-traumatic injuries; and other inflammatory tendon, joint and muscular afflictions, still represent unmet medical needs. Cetylated fatty acids (CFAs) are key components of widely distributed over-the-counter products, especially for topical use, which are intended to reduce symptoms associated with these conditions. Nevertheless, the mechanism of action of CFAs’ analgesic and anti-inflammatory properties has not yet been clearly established. Endocannabinoids, such as 2-arachidonoylglycerol (2-AG) and anandamide (AEA), are known to produce analgesic and anti-inflammatory effects. These compounds undergo physiological inactivation operated by several enzymes, including monoacylglycerol lipase (MAGL). We herein demonstrate for the first time that the therapeutic effects of CFAs may be attributable, at least in part, to their MAGL inhibition activities, which induce a local increase in analgesic/anti-inflammatory endocannabinoids in close proximity to the site of administration. These findings pave the way for the development of new potent local analgesic agents, whose action is based on an indirect cannabinoid effect. Full article

Tendinopathy is often described as a complex and multifactorial condition which affects tendons. Tendon disorders are marked by a reduction in mechanical function, accompanied by pain and swelling. At the molecular level, tendinopathy leads to oxidative stress-driven inflammation, increased cell death, disruption of extracellular matrix balance, abnormal growth of capillaries and arteries, and degeneration of collagen formation. Here, we report an innovative approach to modulate oxidative stress during tendinopathy based on sulfonamide-based Carbonic Anhydrase Inhibitors—carbon monoxide releasing molecules (CAI–CORMs) hybrids endowed with dual carbon monoxide (CO) releasing activity and carbonic anhydrase (CA) inhibition. The synthesised compounds have been studied in a model of human Achilles tendon-derived cells stimulated by H₂O₂. Among the library, compound 1c and, to a greater extent, compound 1a, showed to be extremely effective in terms of restoration of cell metabolic activity and cell proliferation due to their capacity to release CO and inhibit the CA isoforms involved in inflammatory processes in the nanomolar range. Moreover, 1a can restore collagen type 1 secretion under pro-oxidant conditions. Full article

Background: Non-calcific supraspinatus tendinopathy (SNCCT) is a frequent cause of shoulder pain, often associated with functional impairment and reduced quality of life. Recent advancements in diagnostic imaging, including shear wave elastography (SWE), provide quantitative data on tendon stiffness and thickness, facilitating more precise evaluations. Extracorporeal shockwave therapy (ESWT) has emerged as a minimally invasive and effective treatment for SNCCT, but its effects on tendon properties measured through SWE require further investigation. Objective: This retrospective observational study aimed to evaluate the impact of ESWT on supraspinatus tendon characteristics in patients with SNCCT by assessing tendon thickness, SWE velocity, and clinical outcomes. Methods: This observational study enrolled 39 patients with SNCCT, aged 30–75 years, who received three ESWT sessions over 3 weeks. The intervention was delivered using a Modulith SLK system at an energy level of 0.20 mJ/mm² with 2400 pulses per session. SWE and conventional ultrasound were used to measure tendon thickness and SWEv at baseline (T0) and 6 months post-treatment (T1). Clinical outcomes were assessed using the Visual Analog Scale (VAS), Constant and Murley Score (CMS), and modified Roles and Maudsley scale. Data were analyzed using paired t-tests and correlation analyses. Results: At baseline, affected tendons exhibited increased thickness (7.5 ± 0.9 mm) and reduced SWEv (3.1 ± 0.7 m/s) compared to healthy tendons (4.5 ± 0.7 mm and 6.9 ± 1 m/s, respectively; p < 0.05). Six months after ESWT, tendon thickness decreased significantly (6.2 ± 0.9 mm, p < 0.05), and SWEv increased (5.7 ± 1.8 m/s, p < 0.05), indicating improved elasticity. Clinical outcomes improved significantly, with the VAS scores decreasing from 6.5 ± 1.4 to 3.2 ± 2.1, the CMS score rising from 59.1 ± 17.3 to 78.2 ± 17.7, and the modified Roles and Maudsley scale improving from 2.3 ± 0.6 to 1.5 ± 0.8 (p < 0.05 for all). SWEv positively correlated with the CMS (r = 0.4) and negatively with the VAS and the modified Roles and Maudsley scale (r = −0.6 and r = −0.5, respectively). Conclusions: ESWT significantly reduces tendon thickness and enhances elasticity, correlating with improvements in pain and functional scores. SWE proved to be a reliable method for monitoring structural and clinical changes in SNCCT. Further research, including randomized controlled trials, is recommended to confirm these findings and explore longer-term outcomes. Full article