Search Results (455)

A 9-year-old Yorkshire terrier was brought to the emergency department for inability to maintain the correct station with acute onset. Neurological examination showed a non-ambulatory tetraparesis, spontaneous proprioceptive deficit in all limbs, and decreased flexor reflex in the forelimbs. The neurological symptoms suggested a cranial cervical spinal cord with suspicion of spinal shock. The clinical differential diagnoses included degenerative (intervertebral disc extrusion), vascular, inflammatory, or neoplastic disease. No pathological findings were evident in the hematobiochemical tests or in the radiograph examination. MRI examination of the cervical spine showed the presence of two adjacent hydrated nucleus pulposus extrusions at C3-C4 and C4-C5 tracts. Treatment included analgesic and non-steroidal anti-inflammatory therapy; movement restriction was initially necessary, followed by physiotherapy. Follow-up at 4 weeks showed complete recovery. A telephone follow-up after 3 months with the owner confirmed the absence of symptoms. This article reports the first double cervical HNPE case in a dog, adding the possibility that the disease may present in this form and the success of conservative treatment as described in the literature. Full article

Discogenic low back pain (LBP) is a significant clinical condition arising from degeneration of the intervertebral disc, a common yet complex cause of chronic pain, defined by fissuring in the annulus fibrosus resulting in vascularization of growing granulation tissue and growth of nociceptive nerve fibers along the laceration area. This paper delves into the anatomical and pathophysiological underpinnings of discogenic LBP, emphasizing the role of intervertebral disc degeneration in the onset of pain. The pathogenesis is multifactorial, involving processes like mitochondrial dysfunction, accumulation of advanced glycation end products, and pyroptosis, all contributing to disc degeneration and subsequent pain. Despite its prevalence, diagnosing discogenic LBP is challenging due to the overlapping symptoms with other forms of LBP and the absence of definitive diagnostic criteria. Current diagnostic approaches include clinical evaluations, imaging techniques, and the exploration of potential biomarkers. Treatment strategies range from conservative management, such as physical therapy and pharmacological interventions, to more invasive procedures such as spinal injections and surgery. Emerging therapies targeting molecular pathways involved in disc degeneration are under investigation and hold potential for future clinical application. This paper highlights the necessity of a multidisciplinary approach combining clinical, imaging, and molecular data to enhance the accuracy of diagnosis and the effectiveness of treatment for discogenic LBP, ultimately aiming to improve patient outcomes. Full article

Background/Objectives: Biological products are emerging as therapeutic management options for intervertebral disc (IVD) degenerative affections and lower back pain. Autologous and allogeneic cell therapy protocols have been clinically implemented for IVD repair. Therein, several manufacturing process design considerations were shown to significantly influence clinical outcomes. The primary objective of this study was to preclinically qualify (chondrogenic potential, safety, resistance to hypoxic and inflammatory stimuli) cryopreserved primary progenitor cells (clinical grade FE002-Disc cells) as a potential cell source in IVD repair/regeneration. The secondary objective of this study was to assess the cell source’s delivery potential as cell spheroids (optimization of culture conditions, potential storage solutions). Methods/Results: Safety (soft agar transformation, β-galactosidase, telomerase activity) and functionality-related assays (hypoxic and inflammatory challenge) confirmed that the investigated cellular active substance was highly sustainable in defined cell banking workflows, despite possessing a finite in vitro lifespan. Functionality-related assays confirmed that the retained manufacturing process yielded strong collagen II and glycosaminoglycan (GAG) synthesis in the spheroids in 3-week chondrogenic induction. Then, the impacts of various process parameters (induction medium composition, hypoxic incubation, terminal spheroid lyophilization) were studied to gain insights on their criticality. Finally, an optimal set of technical specifications (use of 10 nM dexamethasone for chondrogenic induction, 2% O₂ incubation of spheroids) was set forth, based on specific fine tuning of finished product critical functional attributes. Conclusions: Generally, this study qualified the considered FE002-Disc progenitor cell source for further preclinical investigation based on safety, quality, and functionality datasets. The novelty and significance of this study resided in the establishment of defined processes for preparing fresh, off-the-freezer, or off-the-shelf IVD spheroids using a preclinically qualified allogeneic human cell source. Overall, this study underscored the importance of using robust product components and optimal manufacturing process variants for maximization of finished cell-based formulation quality attributes. Full article

Artificial intelligence has garnered significant attention in recent years as a rapidly advancing field of computer technology. With the continual advancement of computer hardware, deep learning has made breakthrough developments within the realm of artificial intelligence. Over the past few years, applying deep learning architecture in medicine and industrial anomaly inspection has significantly contributed to solving numerous challenges related to efficiency and accuracy. For excellent results in radiological, pathological, endoscopic, ultrasonic, and biochemical examinations, this paper utilizes deep learning combined with image processing to identify spinal canal and vertebral foramen dimensions. In existing research, technologies such as corrosion and expansion in magnetic resonance image (MRI) processing have also strengthened the accuracy of results. Indicators such as area and Intersection over Union (IoU) are also provided for assessment. Among them, the mean Average Precision (mAP) for identifying intervertebral foramen (IVF) and intervertebral disc (IVD) through YOLOv4 is 95.6%. Resnet50 mixing U-Net was employed to identify the spinal canal and intervertebral foramen and achieved IoU scores of 79.11% and 80.89%. Full article

Background/Objectives: Cutibacterium acnes (C. acnes), formerly known as Propionibacterium acnes (P. acnes), is an anaerobic, low-virulent bacterium that has been associated with postoperative infections of the shoulder, knee, and cervical spine. Recent studies have highlighted an association between C. acnes and the development of degenerative disc disease (DDD). The aim of this study is to ascertain whether C. acnes increases the risk of subsidence following anterior cervical discectomy and fusion (ACDF). Methods: After IRB approval, consecutive patients undergoing elective ACDF for DDD from 2017 to 2018 were enrolled in this prospective cohort study. Intervertebral disc samples were taken at each affected level and cultured. A total of 66 patients with radiographic follow-ups were included in the final analysis. The extent of subsidence and cervical lordosis was determined immediately postoperatively and at the 3- and 6-month follow-ups. Results: No significant difference in subsidence was observed at 3 months (p = 0.07) or 6 months (p = 0.11) between culture-positive and -negative cohorts. Additionally, there was no significant difference detected in the change in cervical lordosis observed at 3 months (p = 0.16) or 6 months (p = 0.27) between culture-positive and -negative cohorts. For the most inferiorly fused segment, there was a significant difference in subsidence observed at 3 months (1.5 mm, 95% CI: 0.2–2.7 mm, p = 0.02) but not at 6 months (p = 0.17). Conclusions: Intervertebral discs with a positive C. acnes culture were not associated with greater levels of subsidence at 3 or 6 months following ACDF for DDD. Further research is necessary to endorse these results and to gauge the clinical significance of C. acnes infection. Full article

Intervertebral disc disease (IVDD) is a very common cause of spinal cord compression in dogs. The errors of human surgeons operating on the wrong level or wrong side is a recognized problem and has been largely analyzed. To date, little information is available regarding these errors in dogs. The objective of this study was to assess the accuracy of disc localization prior to possible surgery for IVDD to ensure the surgeon begins their incision directly over the extruded disc. Eighty-five chondrodystrophic or brachycephalic dogs that presented with IVDD confirmed by CT or MRI scan were included in the study. Two small Backhaus clamps were placed cranial and caudal to the lesion site and a control clamp placed at the wing of the ilium. The main interest was whether the surgeon was able to preoperatively pinpoint the correct site for the surgery. Dorsoventral radiographs were taken to verify by another person if the clamps had been placed in the correct position. If the result was incorrect, the surgeon was asked to try again without knowing that the clamps were incorrect, and another radiograph was taken. This was repeated until the position was correct. The results were recorded as correct or incorrect and the number of attempts were registered. The results suggested no significant trend over time for any of the outcomes examined. There were some slight improvements over time, but none of the results was close to statistical significance. The findings of the study showed that in the thoracolumbar region the surgeon has a higher chance of incorrectly marking the exact site for surgery. Full article

Intervertebral disc degeneration in dogs occurs in an accelerated way and involves calcification, which is associated with disc herniation or extrusion. The degenerative process is complex and involves the transformation of collagen fibres, loss of proteoglycans and notochord cells and a reduction in water content; however, how these processes are linked to future disc extrusion remains unknown. We have employed techniques including Fourier Transform Infra-red Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Uniaxial Compression Loading and Atomic Force Microscopy (AFM) in an attempt to gain a greater understanding of the degenerative process and its consequences on the physical properties of the disc. FTIR verified by TEM demonstrated that calcium phosphate exists in an amorphous state within the disc and that the formation of crystalline particles of hydroxyapatite occurs prior to disc extrusion. AFM identified crystalline agglomerates consistent with hydroxyapatite as well as individual collagen fibres. SEM enabled the identification of regions rich in calcium, phosphorous and oxygen and allowed the visualization of the topographical landscape of the disc. Compression testing generated stress/strain curves which will facilitate investigation into disc stiffness. Ongoing work is aimed at identifying potential areas of intervention in the degenerative process as well as further characterizing the role of calcification in disc extrusion. Full article

As part of the spine, the vertebral canal represents a central structure protecting the spinal cord running within it. Since alterations to the spinal canal and adjacent structures can have a significant impact on the spinal cord, knowledge of the physiological vertebral canal dimensions is essential. Compression of spinal nerves at the lumbosacral junction is the primary cause of cauda equina syndrome (CES). Although CES is common in dogs, it is rarely documented in cats. Given the lack of information on normal vertebral canal dimensions in cats, it is necessary to collect data and verify currently used measurements, to determine if and to what extent comparisons with dogs are valid. In 50 cats, interpedicular (ID) and midsagittal (SD) diameters were examined from the first thoracic (Th1) to the first sacral vertebra (S1). In 28 of these animals, the intervertebral disc width (IVDW) was measured. All data were gathered through gross anatomical dissection of the cats. Significant lumen reduction was evident in all cats from L6 to S1 with the narrowest point at S1. Narrowings were also found in the thoracic spine. The widest points coincide with the spinal cord enlargements. IVDW shows relatively constant values up to Th10–Th11 and peaks at L7–S1 in 95.65% of cats. While distinct similarities to dogs were observed, differences exist. The findings allow conclusions as to whether relations between the parameters and resulting predispositions to pathological changes can be derived. This could help the understanding of the pathogenesis of feline spinal diseases, particularly compressive myelopathies. Further studies are necessary to investigate the impact of age, sex and breed. Full article

Several authors have advocated for the role of physiotherapy in canine intervertebral disc extrusion, and it is routinely recommended by various veterinary neurologists. However, veterinary literature does not unanimously support the routine use of physiotherapy to ensure an increase in locomotor return in dogs with IVDE. The aim of the study was to investigate whether physiotherapy can influence the functional recovery of paraplegic dogs with loss of nociception (LN) affected by thoracolumbar IVDE (Hansen type I) and treated surgically. The animals were divided into two groups: the physiotherapy group (PG), which included those that underwent decompressive surgery and postoperative physiotherapy; and the control group (CG), which included dogs that did not undergo any physiotherapy after surgery. A total of 51 dogs were included, with 30 in the PG and 21 in the CG. The number of physiotherapy sessions ranged from 6 to 60. The rate of functional recovery in dogs within 21 days postoperatively (PO) was 10% (3/30) in the PG and 19% (4/21) in the CG. After 21 days PO, the recovery rate was 43.33% (13/30) in the PG and 61.9% (13/21) in the CG, with no significant difference observed between the groups (p = 0.258). Based on the findings of this study, it was concluded that physiotherapy in paraplegic dogs with LN due to thoracolumbar IVDE does not appear to influence functional recovery compared to the group without physiotherapy. Full article

Intervertebral disc (IVD) degeneration is one of the primary causes of low back pain, causing disability; hence, there is no regenerative nature of the current treatments. Hyaluronic acid (HA) was reported to facilitate tissue repair and alleviate pain. Herein, we determined the therapeutic effect of HA and type II collagen (COLII) hydrogel for tissue repair targeting pain in IVD degeneration. We implanted HA/COLII hydrogel following surgically induced disc injury at coccygeal levels in the rat tail model of pain. We assessed the efficacy of the HA/COLII hydrogel in reducing pain behaviour by using the von Frey assessment, protein expression of growth-associated protein (GAP) 43 for sensory nerve innervation, and disc hydration by magnetic resonance imaging (MRI). We observed the anti-nociceptive effect of the HA/COLII hydrogel in alleviating mechanical allodynia in rats. There was an inhibition of sensory hyperinnervation indicated by the GAP43 protein in the treatment group. We revealed an increase in T1ρ mapping of MRI, indicating that the hydrogel restored disc hydration in vivo. Our findings suggest the HA/COLII hydrogel alleviates pain behaviour, inhibits hyperinnervation and promotes disc hydration for tissue repair, implying that it is a potential candidate for the treatment of degenerative disc-associated low back pain. Full article

Background: While MRI is the primary diagnostic tool for the diagnosis of spondylodiscitis, the role of [¹⁸F]-fluorodeoxyglucose ([¹⁸F]FDG) PET/CT is gaining prominence. This study aimed to determine the frequency of [¹⁸F]FDG PET/CT usage and its impact on the in-hospital mortality rate in patients with spondylodiscitis, particularly in the geriatric population. Methods: We conducted a Germany-wide cross-sectional study from 2019 to 2021 using an open-access, Germany-wide database, analyzing cases with ICD-10 codes M46.2-, M46.3-, and M46.4- (‘Osteomyelitis of vertebrae’, ‘Infection of intervertebral disc (pyogenic)’, and ‘Discitis unspecified’). Diagnostic modalities were compared for their association with in-hospital mortality, with a focus on [¹⁸F]FDG PET/CT. Results: In total, 29,362 hospital admissions from 2019 to 2021 were analyzed. Of these, 60.1% were male and 39.9% were female, and 71.8% of the patients were aged 65 years and above. The overall in-hospital mortality rate was 6.5% for the entire cohort and 8.2% for the geriatric subgroup (p < 0.001). Contrast-enhanced (ce) MRI (48.1%) and native CT (39.4%) of the spine were the most frequently conducted diagnostic modalities. [¹⁸F]FDG PET/CT was performed in 2.7% of cases. CeCT was associated with increased in-hospital mortality (OR = 2.03, 95% CI: 1.90–2.17, p < 0.001). Cases with documented [¹⁸F]FDG PET/CT showed a lower frequency of in-hospital deaths (OR = 0.58, 95% CI: 0.18–0.50; p = 0.002). This finding was more pronounced in patients aged 65 and above (OR = 0.42, 95% CI: 0.27–0.65, p = 0.001). Conclusions: Despite its infrequent use, [¹⁸F]FDG PET/CT was associated with a lower in-hospital mortality rate in patients with spondylodiscitis, particularly in the geriatric cohort. This study is limited by only considering data on hospitalized patients and relying on the assumption of error-free coding. Further research is needed to optimize diagnostic approaches for spondylodiscitis. Full article

Intervertebral disc disease (IDD) is a debilitating spine condition that can be caused by intervertebral disc (IVD) damage which progresses towards IVD degeneration and dysfunction. Recently, human pluripotent stem cells (hPSCs) were recognized as a valuable resource for cell-based regenerative medicine in skeletal diseases. Therefore, adult somatic cells reprogrammed into human induced pluripotent stem cells (hiPSCs) represent an attractive cell source for the derivation of notochordal-like cells (NCs) as a first step towards the development of a regenerative therapy for IDD. Utilizing a differentiation method involving treatment with a four-factor cocktail targeting the BMP, FGF, retinoic acid, and Wnt signaling pathways, we differentiate CRISPR/Cas9-generated mCherry-reporter knock-in hiPSCs into notochordal-like cells. Comprehensive analysis of transcriptomic changes throughout the differentiation process identified regulation of histone methylation as a pivotal driver facilitating the differentiation of hiPSCs into notochordal-like cells. We further provide evidence that specific inhibition of histone demethylases KDM2A and KDM7A/B enhanced the lineage commitment of hiPSCs towards notochordal-like cells. Our results suggest that inhibition of KDMs could be leveraged to alter the epigenetic landscape of hiPSCs to control notochord-specific gene expression. Thus, our study highlights the importance of epigenetic regulators in stem cell-based regenerative approaches for the treatment of disc degeneration. Full article

Biomaterials, such as hydrogels, have an increasingly important role in the development of regenerative approaches for the intervertebral disc. Since animal models usually resist biomaterial injection due to high intradiscal pressure, preclinical testing of the biomechanical performance of biomaterials after implantation remains difficult. Papain reduces the intradiscal pressure, creates cavities within the disc, and allows for biomaterial injections. But papain digestion needs time, and cadaver experiments that are limited to 24 h for measuring range of motion (ROM) cannot not be combined with papain digestion just yet. In this study, we successfully demonstrate a new organ culture approach, facilitating papain digestion to create cavities in the disc and the testing of ROM, neutral zone (NZ), and disc height. Papain treatment increased the ROM by up to 109.5%, extended NZ by up to 210.9%, and decreased disc height by 1.96 ± 0.74 mm. A median volume of 0.73 mL hydrogel could be injected after papain treatment, and histology revealed a strong loss of proteoglycans in the remaining nucleus tissue. Papain has the same biomechanical effects as known from nucleotomies or herniations and thus creates a disc model to study such pathologies in vitro. This new model can now be used to test the performance of biomaterials. Full article

Introduction: The vertebral cartilage endplate (CEP), crucial for intervertebral disc health, is prone to degeneration linked to chronic low back pain, disc degeneration, and Modic changes (MC). While it is known that disc cells express toll-like receptors (TLRs) that recognize pathogen- and damage-associated molecular patterns (PAMPs and DAMPs), it is unclear if CEP cells (CEPCs) share this trait. The CEP has a higher cell density than the disc, making CEPCs an important contributor. This study aimed to identify TLRs on CEPCs and their role in pro-inflammatory and catabolic gene expression. Methods: Gene expression of TLR1–10 was measured in human CEPs and expanded CEPCs using quantitative polymerase chain reaction. Additionally, surface TLR expression was measured in CEPs grouped into non-MC and MC. CEPCs were stimulated with tumor necrosis factor alpha, interleukin 1 beta, small-molecule TLR agonists, or the 30 kDa N-terminal fibronectin fragment. TLR2 signaling was inhibited with TL2-C29, and TLR2 protein expression was measured with flow cytometry. Results: Ex vivo analysis found all 10 TLRs expressed, while cultured CEPCs lost TLR8 and TLR9 expression. TLR2 expression was significantly increased in MC1 CEPCs, and its expression increased significantly after pro-inflammatory stimulation. Stimulation of the TLR2/6 heterodimer upregulated TLR2 protein expression. The TLR2/1 and TLR2/6 ligands upregulated pro-inflammatory genes and matrix metalloproteases (MMP1, MMP3, and MMP13), and TLR2 inhibition inhibited their upregulation. Endplate resorptive capacity of TLR2 activation was confirmed in a CEP explant model. Conclusions: The expression of TLR1–10 in CEPCs suggests that the CEP is susceptible to PAMP and DAMP stimulation. Enhanced TLR2 expression in MC1, and generally in CEPCs under inflammatory conditions, has pro-inflammatory and pro-catabolic effects, suggesting a potential role in disc degeneration and MC. Full article