Caterina Fede

Lumbar spinal stenosis (LSS) is a major cause of pain and disability, yet its pathophysiology remains incompletely understood. Although spinal decompression is the standard surgical treatment for LSS with disabling pain or with progressive neurological symptoms, clinical outcomes are often suboptimal, with reoperation required in 5–23% of cases. While degenerative changes in the vertebral canal have been extensively investigated, the potential contribution of the thoracolumbar fascia (TLF) has never been explored at the molecular level. We hypothesized that TLF undergoes extracellular matrix remodeling and inflammatory changes in LSS. Thoracolumbar fascia biopsies were collected from 14 patients undergoing spinal surgery (seven with LSS and seven controls with traumatic vertebral fractures). Total collagen content was quantified by hydroxyproline assay; collagen subtypes (I, III, VI and XII) by Western blotting; and inflammatory activity and extracellular matrix remodeling by ELISA quantification of TNF-α and MMP-2. LSS patients showed significantly higher hydroxyproline content (p = 0.026), indicating increased collagen deposition and fibrotic fascial remodeling, together with elevated MMP-2 levels (p = 0.038), consistent with active chronic extracellular matrix remodeling. TNF-α levels did not differ significantly between groups, although marked inter-individual variability was observed. Collagen subtype expression showed distinct trends but no significant differences. These findings provide the first molecular evidence of fibrotic remodeling and altered extracellular matrix turnover in TLF of LSS patients, supporting its role as an active contributor to disease pathophysiology and a potential diagnostic biomarker and therapeutic target.

Proprioceptive dysfunction is a common rehabilitation issue in neurological injury, and the muscle spindle (MS) is considered a critical structure in this dysfunction. The present study aimed to investigate the morphological alterations of MS in two classical neurological diseases: denervation and stroke, and to understand the role of MS in these two diseases preliminarily. The denervation and stroke model animals were constructed by using a surgical operation and middle cerebral artery occlusion (MCAO) protocol, respectively. The muscles from the affected-side limb and the healthy-side limb were harvested and then fixed, embedded, sliced, stained, and subjected to other laboratory analysis at the predetermined time point. The capsule thickness, cross-sectional area (CSA) of intrafusal fiber and extrafusal fiber, the collagen area percentage, and the hyaluronic acid were investigated in the denervation and stroke animal model. In denervation rats, the capsule thickness in the denervation-side limb increased significantly with the p value under 0.01, while the CSA of intrafusal fiber and extrafusal fiber both decreased with the p values under 0.01 and 0.0001, respectively, compared to the healthy-side. The collagen area percentage increased on the denervation side, with a p value under 0.01, but no difference was found in hyaluronic acid. In stroke mice, similar tendencies were found in the stroke-affected side regarding the capsule thickness and CSA of intrafusal fiber, but there was no statistical significance. The CSA of extrafusal fiber seems equal on the stroke-affected side and healthy-side as well as the collagen area percentage. The hyaluronic acid in the capsule of MS was higher in affected-side compared to healthy-side with a p value under 0.05. The alterations of MSs suggested that MS’s roles in proprioception are diverse in these two typical neurological diseases. The changes of MS in denervation are aligned with the alterations of muscle and intramuscular connective tissue, but are not aligned in stroke, especially the hyaluronic acid. The present study provides a novel MS-based view to understand proprioception dysfunction in stroke and peripheral nerve injury.

Lumbar spinal stenosis (LSS) is a major cause of pain and disability, yet its pathophysiology remains incompletely understood. Although spinal decompression is the standard surgical treatment for LSS with disabling pain or with progressive neurological symptoms, clinical outcomes are often suboptimal, with reoperation required in 5-23% of cases. While degenerative changes of the vertebral canal have been extensively investigated, the potential contribution of the thoracolumbar fascia (TLF) has never been explored at the molecular level. We hypothesized that the TLF undergoes extracellular matrix remodeling and inflammatory changes in LSS. Thoracolumbar fascia biopsies were collected from 14 patients undergoing spinal surgery (7 with LSS and 7 controls with traumatic vertebral fractures). Total collagen content was quantified by hydroxyproline assay, collagen subtypes (I, III, VI and XII) by Western blotting, and inflammatory remodeling by ELISA quantification of TNF-α and MMP-2. LSS patients showed significantly higher hydroxyproline content (p = 0.026), indicating increased collagen deposition and fascial fibrosis, together with elevated MMP-2 levels (p = 0.038), supporting the presence of active chronic extracellular matrix remodeling. TNF-α levels did not differ significantly between groups, although marked inter-individual variability was observed. Collagen subtype expression showed distinct trends but no significant differences. These findings provide the first molecular evidence of fibrotic remodeling and altered extracellular matrix turnover in the TLF of LSS patients, supporting its role as an active contributor to disease pathophysiology and a potential diagnostic biomarker and therapeutic target.

Background and Objectives: The thoracolumbar fascia (TLF) has been implicated in low back pain, but imaging-based characterization in degenerative lumbar disorders, particularly in surgical cohorts, remains limited. To describe MRI-derived and US-derived TLF thickness estimates in a heterogeneous degenerative lumbar surgical cohort and explore preliminary imaging patterns and associations with selected clinical variables. Materials and Methods: In this prospective single-center cohort, adults scheduled for elective lumbar surgery underwent preoperative US (short- and long-axis at L3) and review of routine lumbar MRI (axial and sagittal T1-weighted measurements at L3) using standardized protocols. Twenty-six patients were included (15 with lumbar spinal stenosis, five with lumbar disc herniation, four with spondylolisthesis, and two with scoliosis). Disability was assessed using the Oswestry Disability Index (ODI). Exploratory subgroup comparisons, correlation analyses, and Bland–Altman agreement analysis were used to examine subgroup patterns, patient–factor associations, and MRI–US agreement. Results: Interpretable data were available for 19 axial MRI, 18 sagittal MRI, 19 short-axis US, 15 long-axis US, and 19 ODI assessments; paired MRI–US measurements were available in 11 cases for sagittal/long-axis analysis and 12 for axial/short-axis analysis. Mean TLF thickness was 0.89 ± 0.33 mm on axial MRI, 1.16 ± 0.48 mm on sagittal MRI, 2.53 ± 1.44 mm on short-axis US, and 2.49 ± 1.14 mm on long-axis US. Exploratory subgroup analyses showed a between-diagnosis difference only for axial-MRI-derived TLF thickness (p = 0.007), with lower thickness in disc herniation than in stenosis (p = 0.008), while sagittal MRI and US thickness measures did not differ between groups (p ≥ 0.301). ODI was not consistently associated with TLF thickness on MRI or US. Conclusions: In this exploratory surgical cohort, US-derived TLF thickness values were higher than those previously reported in the literature, suggesting possible fascial alteration in degenerative lumbar disease. However, TLF thickness was not consistently associated with disability, and MRI- and US-derived measurements should be interpreted as modality-specific estimates rather than interchangeable values. Given the small heterogeneous cohort and measurement constraints, these findings are descriptive and preliminary, but they provide an imaging framework to guide future standardized studies.

This narrative review synthesizes evidence from 108 studies to provide the first comprehensive overview of extracorporeal shockwave therapy (ESWT) for plantar fasciitis across three key domains. First, assessment methodologies were evaluated, identifying 36 distinct tools classified into six categories, including pain (with the Visual Analog Scale being the most frequently used), function (most commonly the Foot Function Index), plantar fascia thickness, and other measures. Second, treatment protocols were analyzed, revealing commonly applied parameters of 2000 impulses per session and an energy flux density of 0.2 mJ/mm² or 3.0 bar. Third, the comparative status of ESWT relative to other interventions was examined. Across 18 alternative treatments, corticosteroid injections, platelet-rich plasma (PRP), dextrose prolotherapy, laser therapy, and ultrasound were the most frequently compared modalities. ESWT and comparator interventions demonstrated differential advantages across specific outcomes; however, these findings cannot be directly translated into clinical recommendations, due to the limitations of the available evidence. By consolidating fragmented data, the present review clarifies the current research landscape and provides a foundational reference to support outcome evaluation and individualized treatment selection.

Background and Objectives: The thoracolumbar fascia (TLF) has been implicated in low back pain, but imaging-based characterization in specific degenerative lumbar pathologies—particularly in surgical cohorts—remains limited. To evaluate TLF thickness on Magnetic resonance imaging (MRI) and Ultrasound (US) across common lumbar pathologies, examine associations with age, body mass index, disability, and assess MRI–US agreement for TLF thickness. Materials and Methods: In this prospective single-centre cohort, adults scheduled for elective lumbar surgery underwent preoperative US (short- and long-axis at L3) and review of routine lumbar MRI (axial and sagittal T1-weighted measurements at L3) using standardized protocols. Disability was assessed using the Oswestry Disability Index (ODI). Group comparisons, correlation analyses, and intraclass correlation coefficients were used to evaluate between-diagnosis differences, patient-factor associations, and MRI–US agreement. Results: Thirty-seven patients were eligible (15 lumbar spinal stenosis, 5 discs herniations, 4 spondylolisthesis, 2 scoliosis, 9 revision surgeries, 2 trauma comparators). Median TLF thickness was 0.86 mm (0.16–1.40) on axial MRI, 1.12 mm (0.47–2.33) on sagittal MRI, 2.38 mm (1.01–5.91) on US short-axis, and 2.87 mm (1.12–5.74) on US long-axis. Axial MRI thickness differed across groups (p=0.010), driven by thinner measurements in trauma versus disc herniation (p=0.031); no significant group effects were observed on sagittal MRI or US. Age correlated positively with axial MRI thickness (p=0.021). No significant correlations were detected between ODI and TLF thickness on MRI or US. MRI–US agreement was poor, indicating the modalities are not interchangeable for TLF thickness measurement. Conclusions: TLF thickness measured on MRI and US did not consistently differentiate diagnostic groups and was not associated with disability. Thickness estimates differed substantially by modality, with poor MRI–US agreement. Larger studies with standardized acquisition and reliability testing are needed to clarify the clinical and mechanistic relevance of TLF imaging in degenerative lumbar disease and to determine whether it can support phenotype-based stratification within degenerative spine disease.

Fascia has traditionally been described as a passive connective tissue mainly composed of collagen types I and III. Recent research, however, has revealed its structural and functional complexity, suggesting the possible presence of additional collagen types. This study aimed to quantify the presence and distribution of collagen types I, III, VI, and XII in human superficial and deep fasciae to improve understanding of fascial extracellular matrix composition. Superficial and deep fascia samples were collected from 19 adult patients (ages 20–83 years; thigh and lumbar area). Histology, Azan Mallory staining, hydroxyproline quantification, Western blotting, and immunohistochemistry were performed. The results indicated that deep fascia contained significantly more total collagen than superficial fascia (0.55 ± 0.17 µg/mg vs. 0.36 ± 0.14 µg/mg, p < 0.01). Collagen type VI was the most abundant and widely distributed subtype in both superficial and deep fasciae (mean ratio equal to 0.24 ± 0.13 and 0.27 ± 0.10, respectively), nearly double that of collagen types I (0.12 ± 0.07 and 0.11 ± 0.08), III (0.13 ± 0.09 and 0.17 ± 0.11), and XII (0.13 ± 0.11 and 0.13 ± 0.04). Moreover, statistically significant anatomical differences were observed, despite considerable interindividual variability. Fasciae from the thigh showed higher levels of collagen types I and III (mean ratio of 0.17 and 0.27, respectively, in deep fascia; 0.14 for both types in superficial fascia), whereas fasciae of the lumbar region exhibited greater levels of collagen types VI and XII (ratio equal to 0.33 and 0.15, respectively, in deep fascia; 0.36 and 0.20 in superficial fascia). Overall, these findings highlighted the structural complexity and regional specialization of human fasciae, with potential functional implications for mechanotransduction and tissue adaptation.

Background: Wound healing contributes to restoring skin integrity. However, scars affect soft tissue in all its layers, including the superficial and deep fascia; moreover, it has been demonstrated that the fibroblasts leading the scarring process develop from progenitors located in the superficial fascia. In the past, research into scar etiology has focused primarily on the dermal and epidermal layers, leaving the role of the fasciae largely overlooked. Many patients presenting with surgical or traumatic scars complain of the increased stiffness and thickness of the scar, reduced extensibility of the area surrounding it, and chronic pain persisting even after the healing process has been completed. The purpose of this systematic review is to investigate the non-invasive tools and methods employed for the objective evaluation of scars that involve fascial layers. Methods: A systematic literature search was conducted on PubMed and WOS. Registration DOI: 10.17605/OSF.IO/SDR3Q. Results: A total of 11 articles were selected; the etiologies of scars were surgical, traumatic, and other (keloids). The investigations were conducted using ultrasound, magnetic resonance imaging, strain elastography, and shear wave elastography on the visceral fasciae, superficial fascia, hypodermis, and musculoskeletal fasciae. Sliding of fasciae was assessed by ultrasound; thickness of fasciae was assessed by ultrasound and magnetic resonance imaging; stiffness was assessed by shear wave elastography and strain elastography; and the qualitative assessment was performed via ultrasound. Conclusions: Our literature review showed that ultrasound, magnetic resonance imaging, strain elastography, and shear wave elastography are currently adopted for investigating the sliding, thickness, stiffness, and qualitative features of scars involving fascial layers. Moreover, our research showed the existence of a gap in the scientific literature on this topic.

Introduction: Muscle hypertonia is a common symptom in patients with upper motor neuron disorders. To date, the role of intramuscular connective tissue (IMCT) alterations in hypertonic muscle has not been fully explored. This review aimed to identify and characterize alterations in IMCT components in hypertonic muscle in central neurological disorders. Methods: This scoping review included studies investigating IMCT alterations in hypertonic muscles resulting from central neurological disorders. Four electronic databases, including PubMed/Medline, CINAHL, Web of Science, and Scopus, were searched to identify relevant studies published prior to 20 July 2025. The review followed the Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist. The risk of bias was evaluated using ROBINS-E. Data were extracted and narratively synthesized according to IMCT categories. Results: Twelve studies were included. Among the included studies, increased collagen, glycosaminoglycan content, fascia thickness, and fibroblasts, as well as altered IMCT structural properties, were found in hypertonic muscles. The collagen content was found to be positively correlated with spasticity and stiffness. A key limitation of these studies is that all participants were in the chronic stage of the neurological disease. Conclusion: This scoping review provides evidence that alterations in IMCT components in muscle with hypertonia occur across different neurological conditions. Targeting these changes may provide a new intervention strategy to reduce muscle stiffness and improve the muscle function of patients with hypertonia secondary to neurological disease.

Fascia has traditionally been described as a passive connective tissue mainly composed of Collagen types I and III. Recent research, however, has revealed its structural and functional complexity, suggesting the possible presence of additional collagen types. This study aimed to quantify the presence and distribution of Collagen types I, III, VI, and XII in human superficial and deep fascia to improve understanding of fascial extracellular matrix composition. Superficial and deep fascia samples were collected from 19 adult patients (ages 20–83 years; thigh and lower back). Histology, Azan Mallory staining, hydroxyproline quantification, Western blotting, and immunohistochemistry were performed. Results indicated that deep fascia contained significantly more total collagen than superficial fascia (0.55 ± 0.17 µg/mg vs. 0.36 ± 0.14 µg/mg, p<0.01). Collagen type VI was the most abundant and diffusely distributed subtype in both superficial and deep fascia (mean ratio equal to 0.24 ± 0.13 and 0.27 ± 0.10, respectively), nearly double that of Collagen types I (0.12 ± 0.07 and 0.11 ± 0.08), III (0.13 ± 0.09 and 0.17 ± 0.11), and XII (0.13 ± 0.11 and 0.13 ± 0.04). Moreover, statistically significant anatomical differences were observed, although individual variability remained considerable. Fasciae from the thigh showed higher levels of Collagen types I and III (mean ratio of 0.17 and 0.27, respectively, in deep fascia; 0.14 for both types in superficial fascia), whereas fasciae of the low back region exhibited greater levels of Collagen types VI and XII (ratio equal to 0.33 and 0.15, respectively, in deep fascia; 0.36 and 0.20 in superficial fascia). Overall, these findings highlighted the structural complexity and regional specialization of human fasciae, with potential functional implications for mechanotransduction and tissue adaptation.