Search Results (85)

Background: The primary effect of Botulinum toxin (BoNT) is to cause weakness in the injected muscles by inhibiting the release of acetyl choline from presynaptic nerve terminals. Its effect on sensorimotor integration (SMI) has largely been confined to small studies. The aim of this review is to highlight effect of BoNT on SMI in the context of Parkinson’s disease (PD), Cervical dystonia (CD), and Writer’s cramp (WC). Methods: Using keywords “Botulinum toxin” and “sensorimotor integration” or “Freezing of gait (FOG)” or ‘Tremor”or “Cervical dystonia” or “Parkinson’s disease”, or “Writer’s cramp”, PubMed database was searched for relevant articles supporting our view. The abstracts of all resultant articles (case reports, case series, randomized trials, observational studies) were reviewed to look for evidence of effects of botulinum toxin on SMI. The relevant articles were charted in excel sheet for further full text review. Results: In FOG, chronic BoNT injections may alter central motor patterns with inclusion of alternative striatal systems, cerebellum, and its connections. In tremor, the afferent proprioceptive input may be modified with reduction of intracortical facilitation and increment of intracortical inhibition. In CD, BoNT can restore disorganized cortical somatotrophy, the key pathophysiology behind cervical dystonia. Similarly, in WC, both the deficient sensory system and abnormal reorganization of the sensorimotor cortex may be altered following chronic BoNT injections. Conclusions: There is preliminary evidence that BoNT may modulate SMI in PD, CD, and WC by altering inputs from the muscle spindles in short term and modifying circuits/particular anatomic cerebral cortices in the long term. Properly conducted randomized trials comparing BoNT with placebo or prospective large-scale studies to look for effect on various surrogate markers reflective of changes in SMI should be the next step to confirm these findings. Targeting the system of afferents like spindles and golgi tendon organs in muscles may be a better way of injecting BoNT, with lower amounts of toxin needed and potential for lesser side-effects like weakness and atrophy. However, this needs to be proven in controlled trials. Full article

This work investigates the macroscopic behavior of skeletal muscles from a system-theoretic perspective. Based on data available in the literature, we propose an initial evaluation model for isometric force generation, i.e., force produced at a constant muscle length or in quasi-static conditions, as a function of muscle length and neuronal excitation frequency. This model enables a more physics-inspired representation of isometric force by employing a nonlinear spring framework with controllable properties such as stiffness and rest length. Finally, we introduce a hybrid dynamical filter model to describe components of the sensory system responsible for relaying information about muscle length and its rate of change back to the Central Nervous System. As an application case, we present the modeling of the oculomotor system, highlighting the relevance of the proposed modeling approach in a physiologically meaningful control task. Full article

Lacrimal cysts (dacryops), which involve lacrimal tissue, are uncommon in dogs with an obscure/unclear pathogenesis. Compared to the current available literature, this report describes the clinicopathologic and immunohistochemical features of two cases of unusual dacryops in brachycephalic dogs. A three-year-old male Cane Corso was referred with a 1-month history of swelling ventromedial to the left eye associated with blepharospasm and epiphora. Furthermore, a severe lower and upper eyelid entropion and a deep corneal ulcer were present. B-mode ultrasonography and a CT scan revealed a subcutaneous cyst, closely adherent to the maxillary bone. Surgical removal and the correction of entropion were performed. No recurrence and/or complication was detected by seven-year follow-up. Histopathology revealed a cystic structure with single- to double-cell-layered, nonciliated, cuboidal epithelia. Alcian blue stain revealed rare, disseminated goblet cells admixed with epithelial cells. The epithelium was strongly Cytokeratin-positive by immunohistochemistry and appeared lined by several layers of smooth muscle actin (SMA)-positive myoepithelial cells. A 1-year-old male French Bulldog with a 3-month lesion of the third eyelid of the right eye. The lesion (15 mm × 7 mm) beneath the conjunctiva appeared pale-pink, smooth, and multilobulated. Excision was performed by blunt dissection through the conjunctiva on the palpebral surface of the third eyelid. Recovery was uncomplicated, and no recurrence has been noted at three-year follow-up. Cytology of the cystic fluid and histopathology and immunohistochemistry of the cyst wall revealed findings for case 1. To further characterize the SMA-positive spindle cells located directly beneath the cyst-lining epithelium, double-color immunofluorescence for SMA and p63 (a myoepithelial cell marker) was performed on the sample from case 2. The analysis revealed that the SMA-positive cells lacked p63 expression, indicating a non-myoepithelial phenotype. The histological findings in our cases are consistent with previous reports of canine dacryops. The positivity of immunohistochemical staining for SMA in cells directly beneath the epithelium of dacryops in the cases here described in two brachycephalic dogs is consistent with previous reports in dogs and horses but in contrast with a retrospective study about a human dacryops. These results support the conclusion that the pathogenesis of dacryops in dogs should exclude failure of ductular “neuromuscular” contractility. Full article

The current opinion paper puts into perspective how altered microbiota transplanted from Alzheimer’s patients initiates the impairment of the microbiota–gut–brain axis of a healthy recipient, leading to impaired cognition primarily arising from the hippocampus, dysfunctional adult hippocampal neurogenesis, dysregulated systemic inflammation, long-term spatial memory impairment, or chronic pain with hippocampal involvement. This altered microbiota may induce acquired Piezo2 channelopathy on enterochromaffin cells, which, in turn, impairs the ultrafast long-range proton-based oscillatory synchronization to the hippocampus. Therefore, an intact microbiota–gut–brain axis could be responsible for the synchronization of ultradian and circadian rhythms, with the assistance of rhythmic bacteria within microbiota, to circadian regulation, and hippocampal learning and memory formation. Hippocampal ultradian clock encoding is proposed to be through a Piezo2-initiated proton-signaled manner via VGLUT3 allosteric transmission at a distance. Furthermore, this paper posits that these unaccounted-for ultrafast proton-based long-range oscillatory synchronizing ultradian axes may exist not only within the brain but also between the periphery and the brain in an analogous way, like in the case of this depicted microbiota–gut–brain axis. Accordingly, the irreversible Piezo2 channelopathy-induced loss of the Piezo2-initiated ultradian prefrontal–hippocampal axis leads to Alzheimer’s disease pathophysiology onset. Moreover, the same irreversible microdamage-induced loss of the Piezo2-initiated ultradian muscle spindle–hippocampal and cerebellum–hippocampal axes may lead to amyotrophic lateral sclerosis and Parkinson’s disease initiation, respectively. Full article

Gynecologic perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms characterized by the co-expression of melanocytic markers (HMB-45 and Melan-A) and smooth muscle markers (SMA, desmin, and caldesmon). The uterus is the most common organ affected, with approximately 110 cases reported worldwide, while occurrences in the cervix, vagina, ovary, and other gynecologic locations are exceptionally rare. These tumors typically present with nonspecific symptoms such as abnormal uterine bleeding and pelvic pain, often mimicking other uterine neoplasms. Histopathologically, PEComas exhibit epithelioid and spindle cell morphology with variable nuclear atypia, mitotic activity, and characteristic immunohistochemical profiles. Although most PEComas behave benignly, a subset demonstrates malignant potential, associated with larger tumor sizes, an increased mitotic index, necrosis, and vascular invasion; however, standardized diagnostic criteria remain scarce. Molecular alterations frequently involve the mTOR signaling pathway through tuberous sclerosis complex (TSC) 1 and TSC2 gene mutations, offering potential targets for therapy. Surgical resection with clear margins remains the cornerstone of treatment. For advanced or metastatic cases, mTOR inhibitors have shown promising efficacy, whereas the role of radiotherapy remains uncertain. This review aims to synthesize current knowledge regarding the epidemiology, clinical presentation, histologic features, malignant potential, and treatment of uterine PEComas, emphasizing the importance of accurate histopathological classification and molecular profiling to guide individualized therapeutic strategies. Full article

In this paper, we present three log-linear models for comparing spectral density functions (SDFs) of neural spike sequences (NSSs). The logarithmic (ln) ratios of the estimated SDFs are modeled as polynomial expressions with respect to angular frequencies plus residual series with autocorrelated errors. The advantage of the proposed models is that they can be applied within certain frequency ranges. Analysis of point processes in the frequency domain can be performed to obtain estimates of the SDFs of NSSs by smoothing the mean-corrected periodograms using moving average weighting schemes. The weighting schemes may differ in the estimated SDFs. To decorrelate the error terms in the log models, we apply a two-stage method: in the first stage, the error terms are identified by choosing a suitable model, while in the second stage, the reliable estimates of the unknown parameters involved in the polynomial expressions are derived by decorrelating the data. An illustrative example from the field of neurophysiology is described, in which the neuromuscular system of the muscle spindle is affected by three different stimuli: (a) a gamma motoneuron, (b) an alpha motoneuron, and (c) a combination of gamma and alpha motoneurons. It is shown that the effect of the gamma motoneuron on the muscle spindle is shifted by the presence of the alpha motoneuron to lower frequencies in the range of [1.03, 7.6] Hz, whereas the presence of the gamma motoneuron shifts the effect of the alpha motoneuron in two bands of frequencies: one in the range of [13.5, 19.9) Hz and the other in the range of [19.9, 30.8] Hz. Full article

Background: Myopericytoma is a rare benign vascular tumour characterised by concentric spindle cell proliferation around blood vessels, often misdiagnosed due to its resemblance to other soft tissue masses. Dupuytren’s disease (DD), a fibroproliferative disorder of the palmar fascia, causes progressive contractures, typically affecting the ring and little fingers. While these conditions are well-documented individually, their coexistence in the same region is rare and diagnostically challenging. Case Presentation: This report highlights a 67-year-old male with longstanding DD and a recurrent palmar mass initially attributed to fibrosis. Magnetic resonance imaging revealed hallmark vascular features suggestive of myopericytoma, confirmed by histopathological analysis showing spindle cell proliferation and immunohistochemical positivity for alpha-smooth muscle actin and h-caldesmon. Concurrent DD, characterised by fibrosis and activated myofibroblasts, further complicated the clinical picture. Methodology: PubMed, Scopus, Web of Science, and Embase databases were searched from January 1901 to December 2024, and 20 studies were found, reporting 41 cases of myopericytoma in hand and upper extremity. Histopathological analysis consistently showed spindle cell proliferation and smooth muscle actin positivity. Coexistence with DD was rare, highlighting the need for detailed imaging and histological evaluation for accurate diagnosis. Conclusions: This case emphasises the complexity of differentiating overlapping pathologies. Surgical excision of myopericytoma and tailored DD management yielded favourable outcomes. Further research into shared fibroinflammatory pathways, including tumour necrosis factor-alpha and interleukin-6, may enhance diagnostic accuracy and treatment strategies for overlapping conditions. Full article

The intensification of human activities in recent years has led to significant overexploitation of Triplophysa strauchii populations, resulting in a decline in the species’ natural stocks. This underscores the need for research and development initiatives aimed at supporting the recovery and sustainable management of the species. Therefore, this study investigated its biological traits and isozyme characteristics in detail. First, throutigations of fish ecology, the age and growth patterns of T. strauchii were examined. The results revealed that the length of the otoliths was greater than the width and that the intermajor groove was indistinct. The age range of the fish was 0–4 years. A correlation between body length and weight revealed that T. strauchii exhibited isometric growth patterns. In terms of growth parameters, the inflection point in age for T. strauchii was t_i = 3.23. Additionally, to analyze the enzymes lactate dehydrogenase (LDH), malate dehydrogenase (MDH), and esterase (EST) in ten tissues of T. strauchii (liver, muscle, heart, gills, eye, brain, fins, kidneys, gonads, and intestines), vertical plate electrophoresis was performed via polyacrylamide gels. The results of isoenzyme analysis revealed that the LDHA (lactate dehydrogenase A subunit) gene was predominant in all tissues. A maximum of two s-MDH enzyme bands with three m-MDH enzyme bands were detected, with a classic enzyme profile and no gene mutation. The EST enzyme was highly expressed in the liver and kidney and was less polymorphic. In general, T. strauchii exhibited a spindle-like body shape and isometric growth patterns in the Turks River. It exhibited a narrow age range, strong adaptability, and stable genetic traits. This species has high development potential, utilization value and ecological significance. Full article

Background/Objectives: Tentonin-3/TMEM150C is a pore-forming protein of a mechanically activated channel recently identified that typically displays rapid activation followed by slow inactivation. It has been detected in murine dorsal root ganglia, nodose ganglion baroreceptors, and muscle spindles. Nevertheless, primary sensory neurons expressing tentonin-3/TMEM150C fall into the categories of nociceptors, mechanoreceptors, and proprioceptors. Methods: We used immunohistochemistry and image analysis (examining the size of the neuronal bodies in the dorsal root ganglia) to investigate the distribution of tentonin-3/TMEM150C in human cervical dorsal root ganglia, sensory nerve formations in the glabrous skin, especially cutaneous end-organ complexes or sensory corpuscles, and muscle spindles. Results: In dorsal root ganglia, 41% of neurons were tentonin-3/TMEM150C-positive, with a distribution of small (12.0%), intermediate (18.1%), and large (10.9%). In the glabrous skin, tentonin-3/TMEM150C was observed in the axon of Meissner, Pacinian, and Ruffini corpuscles as well as in the axon of the Merkel cell–axon complexes. Furthermore, tentonin-3/TMEM150C-positive axons were observed in muscle spindles. No free nerve endings displaying immunoreactivity were found. Conclusions: This is the first report on the distribution of tentonin-3/TMEM150C immunoreactivity in the human peripheral somatosensory system, and although it is a brief preliminary study, it opens new perspectives for the study of this new mechano-gated ion channel. Full article

Unaccustomed and/or strenuous eccentric contractions are known to cause delayed-onset muscle soreness. In spite of this fact, their exact cause and mechanism have been unknown for more than 120 years. The exploration of the diverse functionality of the Piezo2 ion channel, as the principal proprioceptive component, and its autonomously acquired channelopathy may bring light to this apparently simple but mysterious pain condition. Correspondingly, the neurocentric non-contact acute compression axonopathy theory of delayed-onset muscle soreness suggests two damage phases affecting two muscle compartments, including the intrafusal (within the muscle spindle) and the extrafusal (outside the muscle spindle) ones. The secondary damage phase in the extrafusal muscle space is relatively well explored. However, the suggested primary damage phase within the muscle spindle is far from being entirely known. The current manuscript describes how the proposed autonomously acquired Piezo2 channelopathy-induced primary damage could be the initiating transient neural switch in the unfolding of delayed-onset muscle soreness. This primary damage results in a transient proprioceptive neural switch and in a switch from quantum mechanical free energy-stimulated ultrafast proton-coupled signaling to rapid glutamate-based signaling along the muscle–brain axis. In addition, it induces a transient metabolic switch or, even more importantly, an energy generation switch in Type Ia proprioceptive terminals that eventually leads to a transient glutaminolysis deficit and mitochondrial deficiency, not to mention a force generation switch. In summary, the primary damage or switch is likely an inward unidirectional proton pathway reversal between Piezo2 and its auxiliary ligands, leading to acquired Piezo2 channelopathy. Full article

Objective: The aim of this case report is to show the surgical treatment of cranial fasciitis in a 2-year-old patient. Cranial fasciitis is an uncommon, nonmalignant, and swiftly proliferating lesion that primarily involves the cranium, predominantly in the temporoparietal area. It mostly comprises smooth muscle tissue, connective tissue, and diverse immune cells. The lesion often manifests as an indurated, asymptomatic mass, averaging approximately 2.5 cm in size, although it may exceed 15 cm. Cranial fasciitis predominantly manifests in children below the age of 6. The diagnosis is validated via histological investigation, which identifies a benign tumor defined by the proliferation of spindle-shaped cells organized in a myxoid matrix, frequently displaying a storiform pattern. Methods: We present a case of cranial fasciitis in a 2-year-old pediatric patient, characterized by an atypical manifestation in the maxillary region. The lesion underwent surgical intervention resulting in total excision. Results: Three years after the surgery, the patient is asymptomatic and shows no signs of recurrence. Regular clinical follow-up and imaging are scheduled biannually, and the patient is anticipated to have a favorable long-term prognosis. Conclusions: Cranial fasciitis is a very rare benign lesion that occurs more commonly in childhood. In this case, surgical resection was effective, and three years later, the patient remains asymptomatic and free of recurrence, with a favorable long-term prognosis. Full article

Infantile Fibrosarcoma is a malignant tumor of fibroblastic origin, typically found in early childhood, locally aggressive, and characterized by molecular alterations that activate tyrosine kinase signaling, primarily the ETV6::NTRK3 fusion. In recent years, a series of fusions different from the classic one have been described, including NTRK1, RAF1, and BRAF. In this paper, we present a case of IFS with a novel EVI5::BRAF fusion. We observed a spindle cell neoplasm growing in intertwined fascicles within a fibrous stroma, without the formation of an immature osteoid matrix. Weak and focal immunoreactivity for S100 was observed. SATB2 exhibited diffuse and intense staining, with focal expression of osteonectin and negativity for caldesmon, Smooth Muscle Actin, desmin, GFAP, SOX10, MelanA, panTRK, and HMB45. The Ki67 index was 7%, and the tumor harbored an EVI5::BRAF genetic fusion. To the best of our knowledge, the EVI5::BRAF fusion has not yet been described in BRAF fusions in IFS. Nevertheless, further studies are needed to define the prognostic features of these emerging BRAF sarcomas, along with new anti-BRAF therapeutic approaches. Full article

Objective: Botulinum neurotoxin type A (BoNT/A) injections and the new vibration ergometry training (VET) are studied for their combined effect on improving functional mobility in patients with asymmetric lower limb spasticity. Method: Gait was analyzed using the Infotronic^® system, which measures ground reaction forces and foot contact patterns by means of special force-sensitive shoes strapped over feet or street shoes. Gait was measured several times, depending on the protocol patients underwent. Seven patients with asymmetric lower limb spasticity were analyzed according to the control protocol (CG-group): after a baseline walk of 20 m (NV-W1) patients received their routine BoNT/A injection and had to walk the same distance a second time (NV-W2). Approximately 3–5 weeks later, they had to walk a third time (NV-W3). A further seven patients (VG-group) were analyzed according to the vibration protocol: after a baseline walk (V-W1), patients underwent a first vibration training (VET1), walked a second time (V-W2), received their routine BoNT/A injection, and walked a third time (V-W3). About four weeks later, they had to walk again (V-W4), received another vibration training (VET3), and walked a fifth time (V-W5). At least six months after the analysis according to the vibration protocol, these patients were also analyzed according to the control protocol. Eleven gait parameters were compared between the CG- and VG-group, and within the VG-group. Result: Patients in the VG-group experienced a significant improvement in gait four weeks after BoNT/A injection, unlike the patients in the CG-group. VG-patients also showed improved gait after two VET sessions. However, there was no further functional improvement of gait when BoNT/A injections and VET sessions were combined. Conclusions: BoNT/A injections enhance functional mobility in patients with mild asymmetric leg spasticity. VET also induces an immediate gait improvement and offers a further treatment approach for leg spasticity. Whether combining BoNT treatment and vibration training offers superior outcomes compared to either treatment alone requires further investigation. Full article

Background: Pancreatic cancer is among the malignancies with the poorest prognosis, largely due to its aggressive nature and resistance to conventional therapies. Case Summary: This report describes the case of a 69-year-old male patient with stage IV primary lung adenocarcinoma presenting with high levels of programmed death-ligand 1 (PD-L1). Simultaneously, abdominal computed tomography (CT) showed a dilated pancreatic duct at the level of the pancreatic head and a hypodense lesion in the uncinate process involving the superior mesenteric artery. Fine-needle aspiration (FNA) of the pancreatic lesions was negative. After three cycles of chemoimmunotherapy, positron emission tomography–computed tomography (PET-CT) showed complete remission of the lung nodules, lymphadenopathy, and pleural thickening, as well as a decrease in the size of the pancreatic lesion. After another six months, a PET-CT scan showed a focal increased uptake in the pancreatic mass in the same location, indicating disease progression. A core biopsy of the pancreatic tumor showed atypical spindle cell morphology with positive staining for vimentin, characteristic of mesenchymal differentiation with no apparent epithelial features. Comprehensive molecular profiling through Caris Molecular Intelligence^® revealed four genes with actionable mutations in the pancreatic tissue, including KRAS (p.G12D) and TP53 (p.R175H). These molecular findings suggested the diagnoses of sarcomatoid carcinoma and conventional pancreatic ductal adenocarcinoma with epithelial–mesenchymal transition. Primary mesenchymal tumors and neuroendocrine neoplasms were excluded because immunohistochemistry was negative for anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA), desmin, CD34, signal transducer and activator of transcription 6 (STAT6), S100, HMB45, CD117, discovered on GIST-1 (DOG1), CD56, progesterone, and synaptophysin. However, despite multiple rounds of systemic chemotherapy, immunotherapy, and radiation, his pancreatic disease rapidly deteriorated and metastasized to the liver and bone. Conclusions: Despite multiple lines of treatment, the patient’s condition worsened and he succumbed to his pancreatic malignancy. This study highlights the clinical characteristics, diagnosis, and treatment of rare pancreatic cancer, emphasizing the importance of molecular testing and histopathological biomarkers in personalizing treatment. It also provides insights into promising therapeutic approaches for similar cases with an unusual presentation. Full article

Background/Objective: Short hamstring syndrome is common in the general population and can lead to impaired balance, function, and posture, and increased risk of injuries. Local treatments have obtained controversial results, so it is necessary to evaluate the effectiveness of other types of therapy such as osteopathic treatment. To evaluate the efficacy of osteopathic techniques in increasing the elasticity of the hamstring musculature in short hamstring syndrome. Methods: A systematic review of randomised controlled trials was conducted in PubMed, Medline, Cinhal, Scopus, WOS, SPORTDiscuss, and PEDro. The PEDro scale was used to evaluate the methodological quality and the RoB2 for the evaluation of biases. Results: A total of eight articles were selected. Most of the participants were assessed with the Active Knee Extension or Straight Leg Raise tests. The osteopathic techniques used were the muscle energy technique, suboccipital inhibition, and vertebral mobilisations. As for the control interventions, they mainly included passive stretching and placebo. Conclusions: The results suggest that osteopathic techniques are more effective than placebo or other interventions in increasing flexibility in adult patients with short hamstring syndrome. This effect can be explained by neurophysiological (Golgi apparatus, neuromuscular spindle activity, and Hoffmann reflex) and structural factors (dura mater, posture, and myofascial chains). Nevertheless, the evidence suggests that it would be beneficial to incorporate this type of treatment into flexibility improvement programmes. Full article