Search Results (80)

Background: Spasticity is a complex and multifactorial condition resulting from upper motor neuron injury. It manifests through muscle contractions, pain, limited range of motion, and clonus, which significantly impair daily activities and quality of life. High-frequency spinal cord stimulation (HF SCS) has shown optimal results in treating chronic neuropathic pain, but its potential role in spasticity remains underexplored. This study aimed to evaluate the efficacy of HF SCS in patients with spasticity. Methods: From April 2021 to July 2024, six patients with spasticity from various etiologies underwent SCS implantation at our institution. Clinical evaluations including the use of the Visual Analog Scale (VAS), Douleur Neuropathique 4 (DN4), and the Ashworth score, as well as ambulation ability and clonus episodes, were performed preoperatively and at a minimum of six months post-surgery. Subjective assessments of motor function, including coordination, movement efficiency, and postural transitions, were also recorded. Results: The mean age of patients was 50.12 ± 9.41 years, with follow-up averaging 24.32 ± 10.83 months. Statistically significant improvements were observed in VAS (p = 0.0412) and DN4 (p = 0.0422) scores, alongside a reduction in clonus episodes. All patients reported subjective improvements in coordination, movement efficiency, and postural transitions. Ambulation remained stable or improved in all cases. No perioperative complications or sensory/motor side effects were noted. Conclusions: HF SCS offers a promising approach to managing spasticity, with improvements in motor function, ambulation, and postural transitions. These findings support further investigation into HF SCS for spasticity, with multicenter trials needed to optimize treatment protocols and identify the most responsive patient populations. Full article

Neuropathic pain represents a critical challenge in medical research and clinical practice. Enhanced peripheral nerve activity and spinal dorsal horn neuronal firing are thought to contribute to the nociceptive hypersensitivities that are observed in chronic pain conditions, including those modeled by partial sciatic nerve ligation (PSNL). However, the detailed in vivo neuronal response dynamics and underlying mechanisms in the PSNL model remain to be fully clarified. To better understand these mechanisms, we evaluated dorsal root ganglion (DRG) and spinal dorsal horn neuronal activity in the PSNL model using in vivo approaches. Von Frey testing revealed sustained mechanical allodynia in PSNL animals; withdrawal thresholds were significantly reduced up to day 14 post-surgery. Immunohistochemistry revealed a stimulation-dependent increase in phosphorylated extracellular signal-regulated kinase (pERK)-positive neurons in the DRG, thereby indicating heightened peripheral nerve activity. Additionally, electrophysiological recordings demonstrated the enhanced firing of spinal dorsal horn neurons in response to the same stimuli. Notably, DRG pERK expression changes correlated with spinal neuronal firing frequency. Together, these findings suggest that peripheral nerve activity drives spinal neuronal sensitization, thus elucidating both pain mechanisms in the PSNL model and activity-dependent signaling in neuropathic pain. Full article

Background/Objectives: Spinal cord stimulation (SCS) is an established therapy for chronic pain, but uncertainties remain regarding long-term real-world outcomes and the role of standardized selection pathways. This study aimed to evaluate real-world, longitudinal outcomes of SCS over 24 months within a structured clinical pathway, focusing on pain intensity, neuropathic symptoms, and health-related quality of life. Methods: A single-center, retrospective observational cohort study was conducted at the Fondazione Istituto G. Giglio (Cefalù, Italy). Data were drawn from the continuing, prospective institutional “SCS Pathway” and included consecutive patients implanted between May 2021 and September 2024. Eligible patients were ≥18 years of age with chronic pain refractory to conventional medical management. Outcomes included pain intensity (VAS, visual analog scale), neuropathic features (DN4, douleur neuropathique 4), and health-related quality of life (EQ-5D, EuroQol 5 Dimensions), assessed at baseline and 3, 6, 12, 18, and 24 months post-implantation. Multilevel models with full information maximum likelihood (FIML) were applied to repeated measures. Results: Seventy-six patients were included (mean age 67.3 ± 10.3 years; 39.5% female). The most frequent diagnoses were post-surgical pain syndrome (42.1%, 32/76) and chronic back and leg pain (40.8%, 31/76). 42.1% (32/76) had previous spine surgery, and 78.9% (60/76) reported neuropathic pain. Across 452 observations, mean VAS scores decreased from 7.9 ± 0.7 at baseline to 3.1 ± 1.1 at 3 months (61% reduction, p < 0.001), with sustained benefit at 24 months (4.5 ± 1.5; 43% reduction, p < 0.001). DN4 scores improved from 7.4 ± 0.8 to 3.2 ± 1.0 at 3 months (56% reduction, p < 0.001), with persistent decreases at 24 months (4.2 ± 1.2; 43% reduction, p < 0.001). EQ-5D improved from 22.8 ± 6.6 at baseline to 70.2 ± 10.6 at 3 months (increase of 208%, p < 0.001), with clinically meaningful gains sustained at 24 months (55.4 ± 13.7, increase of 143%, p < 0.001). Conclusions: In this real-world cohort, SCS therapy results in sustained, clinically significant improvements in pain, neuropathic symptoms, and quality of life. Findings highlight the value of structured selection and follow-up pathways. These data provide a benchmark for multicenter studies linking standardized referral frameworks to long-term, patient-centered outcomes. Full article

We report a rare case of isolated bilateral pedicle fractures in the lumbar spine that occurred without any identifiable risk factors. Such fractures are uncommon, as they are typically accompanied by multiple other fractures. This type of fracture is commonly associated with widely acknowledged predisposing factors, including high-energy trauma, degenerative spine disease, previous spinal surgery, stress-related activities, or osteoporosis. Additionally, some reports suggest these fractures can result from low-energy trauma when underlying conditions such as osteoporosis are present. This report describes a 43-year-old female who presented with gradually aggravating low back pain in the absence of any significant trauma history. Initially, she denied any preceding injury, considering the event too trivial to mention. However, upon detailed history taking, she later recalled minor contact with the edge of her bed two days prior to symptom onset. Conservative management, consisting of administration of painkillers, adequate rest, the use of a brace, and rehabilitation exercises, led to significant improvement, with marked relief of clinical symptoms and fracture healing observed in follow-up imaging. Early identification and appropriate management of isolated pedicle fractures are essential, as delayed diagnosis may lead to chronic pain or long-term sequelae. Furthermore, unilateral fracture can increase mechanical loading on the contralateral pedicle, making it vulnerable to secondary stress injury. Therefore, clinicians must remain alert to the possibility of isolated pedicle fractures even in patients without risk factors. Thorough history taking is also essential, as unrecognized minor trauma may hinder timely diagnosis and optimal outcomes. Full article

Background/Objectives: Spinal decompression surgery shows variable outcomes, with reoperation rates up to 37.5%. Surgeons lack objective intraoperative tools to assess decompression adequacy. Mechanomyography (MMG) measures nerve excitability through mechanical muscle responses to electrical stimulation. While compressed nerves require higher stimulation thresholds, optimal quantification approaches remain undefined. We explored associations between intraoperative MMG threshold changes and six-week pain outcomes, comparing metrics anchored to a 2.0 mA reference threshold versus percentage-based measures. Methods: Prospective exploratory pilot study of 42 patients (112 nerves) undergoing lumbar or cervical decompression. MMG thresholds were recorded pre- and post-decompression. Numeric Pain Scale scores were obtained preoperatively and at six weeks. Three metrics were compared: percentage change, Threshold Reduction Ratio (TRR; measuring proportion of threshold elevation above 2.0 mA eliminated by decompression), and Threshold Excess (TE; residual threshold remaining above 2.0 mA), with TRR and TE anchored to 2.0 mA based on published normal ranges. Results: Among 40 patients with baseline pain, threshold-anchored metrics showed substantially stronger correlations with pain improvement than percentage-based measures (TRR: r = 0.656, p < 0.001 vs. percentage: r = 0.397, p = 0.011). Threshold Excess was associated with a linear dose–response: each 1 mA above 2.0 mA corresponded to 6.3% less pain improvement (p = 0.001). Patients achieving ≤2.0 mA had 6.1-fold increased odds of complete pain relief versus those above 2.0 mA (76.5% vs. 34.8%, p = 0.013). Internal leave-one-out cross-validation suggested internal stability (TRR shrinkage ≈ 9.3%; TE’s dose–response slope remained stable). Conclusions: In this exploratory pilot study, threshold-anchored MMG metrics (TRR and TE) showed stronger correlations with early pain outcomes than percentage-based measures. These exploratory findings require external validation in independent cohorts before clinical implementation. If validated prospectively, these metrics could provide objective, real-time feedback for clinical interpretation to inform surgical decision-making during spinal decompression, enabling surgeons to tailor decompression to individual physiology rather than relying on standardized anatomical criteria. Future work should explore patient-specific threshold targets that account for age, chronicity, and comorbidities. Full article

Diabetic neuropathy is characterized by nerve damage and chronic neuropathic pain and lacks effective treatment. Botulinum neurotoxin type A (BoNT/A), a neurotoxin with established therapeutic use in neurological disorders, has emerged as a potential analgesic agent. This study investigated the effects of a recombinant form of BoNT/A1 (rBoNT/A1) on neuropathic pain induced by spared nerve injury (SNI) in a diabetic mouse model. Thirty-two adult male C57BL/6JRj diabetic mice were subjected to SNI or sham surgery. Fourteen days post surgery, mice received an intraplantar dose of rBoNT/A1 or vehicle. Mechanical allodynia was assessed using von Frey filaments, and spinal cord and sciatic nerve tissues were analyzed via immunohistochemistry and transmission electron microscopy to evaluate glial activation, neurotransmitter receptor expression, and axonal morphology. The results demonstrated that rBoNT/A1 significantly alleviated mechanical allodynia and caused a marked reduction in Iba1-positive microglial activation in the spinal cord, whereas no significant changes were observed in astrocyte (GFAP) density or GABAAR subunit expression. Additionally, rBoNT/A1 treatment did not significantly alter axon diameter, myelin thickness, or C-fiber morphology. In conclusion, intraplantar administration of rBoNT/A1 reduced SNI-induced mechanical allodynia in diabetic mice, potentially by attenuating spinal microglial activation, supporting the therapeutic promise of rBoNT/A1 in managing diabetic neuropathic pain. Full article

Background/Objectives: Lumbosacral transitional vertebra (LSTV) is a common anatomical variant, but its identification on plain radiographs is often inconsistent. This inconsistency can lead to clinical complications such as chronic low back pain, misinterpretation of spinal parameters, and an increased risk of wrong-level surgery. This study aimed to develop and validate a deep learning-based artificial intelligence (AI) model for the automated detection of LSTV on plain lumbar radiographs. Methods: This retrospective observational study included a total of 3116 standing lumbar lateral radiographs. The presence or absence of lumbosacral transitional vertebra (LSTV) was definitively established using whole-spine imaging, CT, or MRI. Multiple deep learning architectures, including DINOv2, CLIP (ViT-B/32), and ResNet-50, were initially evaluated for binary classification of LSTV. Among these, the ResNet-50 model with partial fine-tuning achieved the best test performance and was subsequently selected for fivefold cross-validation using the training set. Model performance was assessed using accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC), and interpretability was evaluated using gradient-weighted class activation mapping (Grad-CAM). Results: On the independent test set of 313 radiographs, the final model demonstrated robust diagnostic performance. It achieved an accuracy of 76.4%, a sensitivity of 85.1%, a specificity of 61.9%, and an AUC of 0.84. The model correctly identified 166 out of 195 LSTV cases and 73 out of 118 normal cases. Conclusions: This AI-based system offers a highly accurate and reliable method for the automated detection of LSTV on plain radiographs. It shows strong potential as a clinical decision-support tool to reduce diagnostic errors, improve pre-operative planning, and enhance patient safety. Full article

Background: Bertolotti syndrome describes a painful lumbosacral transitional vertebra (LSTV) with a pseudoarticulation between an enlarged lateral process of the caudal lumbar vertebra (L5) and ilium or sacrum. It often presents with chronic lower back pain with or without radiculopathy. The current literature emphasizes Bertolotti as a differential diagnosis in young adults. However, it is presumably underdiagnosed in middle-aged and older patients. Treatment ranges from conservative treatment with physiotherapy, infiltration, and radiofrequency ablation to surgical interventions. Case Description: In this case illustration, we present the diagnostic and therapeutic challenges in a 48-year-old female triathlete with persistent left gluteal pain caused by Bertolotti syndrome. When conservative treatment with physiotherapy, infiltrations, thermocoagulation, and radiofrequency ablation of the pseudoarticulation failed, microsurgical reduction of the hypertrophic transverse process was performed. This minimally invasive intervention achieved satisfactory pain relief of at least 70% one year after surgery, allowing the patient to resume her athletic activities. Conclusions: Bertolotti syndrome should be considered a potential differential diagnosis in patients of all ages. Since many patients endure years of misdiagnosis, adequate treatment is crucial upon diagnosis. If conservative measures fail, surgical treatment such as “processectomy” or spinal fusion should be evaluated. This case follows the CARE reporting guidelines. Full article

Background: Chronic postsurgical pain (CPSP) poses a major clinical challenge due to unresolved links between neurotrophic pathways and endoplasmic reticulum (ER) stress. While Neurotrophic Tyrosine Kinase Receptor Type 1 (NTRK1) modulates ER stress in neuropathic pain, its interaction with Insulin-Like Growth Factor II (IGF2) in CPSP remains uncharacterized, impeding targeted therapy. This study defined the spinal NTRK1-IGF2-ER stress axis in CPSP. Methods: Using a skin/muscle incision–retraction (SMIR) rat model, we integrated molecular analyses and intrathecal targeting of NTRK1 (GW441756) or IGF2 (siRNA). Results: SMIR surgery upregulated spinal NTRK1, IGF2, and ER stress mediators. NTRK1 inhibition reduced both NTRK1/IGF2 expression and ER stress, reversing mechanical allodynia. IGF2 silencing attenuated ER stress and pain but did not affect NTRK1, revealing a unidirectional signaling cascade where NTRK1 drives IGF2-dependent ER stress amplification. These findings expand understanding of stress-response networks in chronic pain. Conclusions: We show that spinal NTRK1 drives IGF2-mediated ER stress to sustain CPSP. The NTRK1-IGF2-ER stress axis represents a novel therapeutic target; NTRK1 inhibitors and IGF2 biologics offer non-opioid strategies for precision analgesia. This work advances CPSP management and demonstrates how decoding unidirectional signaling hierarchies can transform neurological disorder interventions. Full article

Background: Transcutaneous Randomized Pulsed Radiofrequency (TCPRF-STP) is a non-invasive therapeutic approach increasingly explored for managing spine-related pain, particularly in cases involving disc herniations and degenerative spine conditions. Objectives: To evaluate the use of transcutaneous PRF-STP in the treatment of spine pathologies and its evolution in short-term follow-up. Methods: This case series examines the outcomes of three patients treated with TCPRF-STP for varying spine pathologies, including lumbar and cervical disc herniations, lumbar stenosis, and radiculopathy. All patients had previously undergone conventional conservative therapies without a satisfactory improvement and were unwilling or unable to undergo invasive procedures. The treatment involved the application of electromagnetic fields through adhesive skin patches at targeted sites. Patients underwent three sessions of TCPRF-STP, with follow-up assessments evaluating pain and MRI. Results: Transcutaneous PRF-STP showed notable reductions in pain (VAS 0 in most cases), improvements in movement, and the restoration of normal daily activities. Follow-up MRI scans demonstrated positive structural changes in the treated discs. Although long-term recurrence occurred in one case, the patient remained active without functional limitations. Conclusions: Transcutaneous PRF-STP offers a promising, minimally invasive alternative for patients seeking to avoid surgery, though further studies with larger cohorts and longer follow-up periods are necessary to establish more robust evidence of its efficacy. This technique could become an important adjunct in managing chronic spinal pain conditions, offering patients an option with minimal risk and hospital demands. Full article

The bidirectional relationship between chronic pain and poor sleep are well reported. Disrupted sleep and chronic pain, either alone or in conjunction, are often associated with poor post-surgical outcomes. However, the relationship between peripheral blood biomarkers and chronic pain and sleep disturbances after orthopedic surgery has not been extensively studied. The goal of this observational prospective study was to conduct an analysis on the relationship of blood cytokines and chemokines with chronic pain and sleep outcomes among US service members undergoing orthopedic surgery. Active-duty service members (N = 114) who underwent orthopedic extremity or spinal surgery were recruited, of whom 69 completed pre-surgery and 64 completed 6-week post-surgery surveys and blood draws. Blood cytokine and chemokine analyses were performed using multiplex immunoassays. Non-parametric correlations with blood cytokine and chemokine showed significant associations with both pre- and post-surgical pain scores whereas no significant correlations were observed with sleep disturbance scores. Increased pain intensity 6 weeks after surgery was positively associated with increased hepatocyte growth factor (ρ_s = 0.11; p < 0.05) and negatively correlated with interleukin-2r (ρ_s= −0.42; p < 0.001). This study found that inflammatory biomarkers are associated with pre- and post-surgical pain but not sleep disturbances. Full article

Effective postoperative pain management remains a major clinical challenge in spinal surgery, with poorly controlled pain affecting up to 50% of patients and contributing to delayed mobilization, prolonged hospitalization, and risk of chronic postsurgical pain. This review synthesizes current and emerging strategies in postoperative spinal pain management, tracing the evolution from opioid-centric paradigms to individualized, multimodal approaches. Multimodal analgesia (MMA) has become the cornerstone of contemporary care, combining pharmacologic agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and gabapentinoids, with regional anesthesia techniques, including erector spinae plane blocks and liposomal bupivacaine. Adjunctive nonpharmacologic modalities like early mobilization, cognitive behavioral therapy, and mindfulness-based interventions further optimize recovery and address the biopsychosocial dimensions of pain. For patients with refractory pain, neuromodulation techniques such as spinal cord and peripheral nerve stimulation offer promising results. Advances in artificial intelligence (AI), biomarker discovery, and nanotechnology are poised to enhance personalized pain protocols through predictive modeling and targeted drug delivery. Enhanced recovery after surgery protocols, which integrate many of these strategies, have been shown to reduce opioid use, hospital length of stay, and complication rates. Nevertheless, variability in implementation and the need for individualized protocols remain key challenges. Future directions include AI-guided analytics, regenerative therapies, and expanded research on long-term functional outcomes. This review provides an evidence-based framework for pain control following spinal surgery, emphasizing integration of multimodal and innovative approaches tailored to diverse patient populations. Full article

Background and Clinical Significance: The coexistence of spinal hemangiomas and dural arteriovenous fistula (SDAVF) is uncommon. Unclear imaging and progressive neurological impairment require early surgical management. Case Presentation: A 76-year-old woman presented with progressive thoracolumbar pain and worsening bladder dysfunction. Magnetic resonance imaging (MRI) of the thoracic spine revealed a round-shape expansive lesion at T11 with spinal cord edema and homogeneous contrast enhancement. Despite a chronic presentation, the subacute progression of bladder dysfunction and spinal cord edema warranted timely intervention. Intraoperatively, a vascular malformation resembling a dural arteriovenous fistula (SDAVF), unrecognized at pre-operative imaging, was found in association, and histological examination confirmed the diagnosis of hemangioma. The mechanism of coexistence remains unclear, although venous hypertension due to fistula could induce vascular malformations. Conclusions: This case emphasizes the importance of thorough imaging, timely intervention and intraoperative assessment in patients presenting with a suspicion of spinal hemangioma; it may also provide awareness of potentially associated concurrent lesions such as SDAVFs, unrecognized at pre-operative imaging, and technical insights during surgery. Full article

Background/Objectives: Lumbosacral spinal stenosis (LSS) is a degenerative condition characterized by narrowing of the spinal canal and associated neuropathic pain. While mechanical compression is well-characterized, the molecular mechanisms contributing to symptom severity remain poorly understood. Neurturin (NRTN), a member of the glial cell line-derived neurotrophic factor family, has emerged as a potential mediator of neural plasticity and nociception, but its role in spinal stenosis is largely unexplored. Methods: We analyzed NRTN mRNA and protein expression in ligamentum flavum samples from 96 patients undergoing surgery for LSS and 85 non-degenerative postmortem controls. Quantification was performed using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry. Pain severity Visual Analog Scale (VAS), body mass index (BMI), diabetes, smoking, and alcohol use were assessed as modulators of NRTN expression. Results: NRTN expression was significantly elevated in LSS patients versus controls at both transcript and protein levels (p < 0.05). NRTN levels positively correlated with pain intensity (VAS; ANOVA p = 0.032 for mRNA, p = 0.041 for protein). Multivariate regression identified BMI (β = 0.50, p = 0.015) and diabetes (β = 0.39, p = 0.017) as independent predictors of increased NRTN expression. Alcohol use also showed a positive association (p = 0.046), while smoking showed no significant independent effect. Conclusions: Neurturin is upregulated in ligamentum flavum tissue from LSS patients and correlates with pain severity and metabolic risk factors. These findings suggest NRTN as a potential biomarker and therapeutic target in degenerative spine disease. Further longitudinal and mechanistic studies are warranted to elucidate its role in chronic pain and neuroinflammation. Full article

Minimal facet and lateral mass fractures of the subaxial cervical spine (C3–C7) are a distinct subset of spinal injuries that present diagnostic and therapeutic challenges. These fractures often result from low-energy trauma or hyperextension mechanisms. They are frequently stable. However, subtle fracture instability and associated soft tissue injuries may lead to delayed instability, neurological compromise, and/or chronic severe pain if not properly identified. Accurate diagnosis relies on a combination of plain radiography, high-resolution computed tomography (CT), and magnetic resonance imaging (MRI) to assess bony and ligamentous integrity. Treatment strategy is determined based on fracture stability, neurological status, and radiographic findings. Most stable fractures can be effectively treated with conservative treatment, allowing for natural healing while minimizing complications. However, when instability is suspected—such as those with significant disc and ligamentous injuries, progressive deformity, or neurological deficits—surgical stabilization may be considered. The presence of vertebral artery injury (VAI) can further complicate management. To mitigate the risk of stroke, a multidisciplinary approach that includes neurosurgery, vascular surgery, and interventional radiology is needed. Surgical treatment aims to restore spinal alignment, maintain stability, and prevent further neurological deterioration with approaches tailored to individual fracture patterns and patient-specific factors. Advances in surgical techniques, perioperative management, and endovascular interventions for VAI continue refining treatment options to improve clinical outcomes while minimizing complications. Despite increasing knowledge of these fractures and associated vascular injuries, optimal treatment strategies remain unclear due to limited high-quality evidence. This review provides a comprehensive analysis of the anatomy, biomechanics, classification, imaging modalities, and treatment strategies for minimal facet and lateral mass fractures in the subaxial cervical spine, highlighting recent advancements in diagnostic tools, therapeutic approaches, and managing vertebral artery injuries. A more precise understanding of the natural history and optimal management of these injuries will help spine specialists refine clinical decision-making and improve patient outcomes. Full article