Evaluation of differences in expression pattern of three isoforms of the transforming growth factor beta in patients with lumbosacral stenosis.

The study investigates molecular changes in the lumbosacral (L/S) spine's yellow ligamentum flavum during degenerative stenosis, focusing on the role of transforming growth factor beta 1-3 (TGF-ß-1-3). Sixty patients with degenerative stenosis and sixty control participants underwent molecular analysis using real-time quantitative reverse transcription reaction technique (RTqPCR), enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemical analysis (IHC). At the mRNA level, study samples showed reduced expression of TGF-ß-1 and TGF-ß-3, while TGF-ß-2 increased by only 4%. Conversely, at the protein level, the study group exhibited significantly higher concentrations of TGF-ß-1, TGF-ß-2, and TGF-ß-3 compared to controls. On the other hand, at the protein level, a statistically significant higher concentration of TGF-ß-1 was observed (2139.33 pg/mL ± 2593.72 pg/mL vs. 252.45 pg/mL ± 83.89 pg/mL; p < 0.0001), TGF-ß-2 (3104.34 pg/mL ± 1192.74 pg/mL vs. 258.86 pg/mL ± 82.98 pg/mL; p < 0.0001), TGF-ß-3 (512.75 pg/mL ± 107.36 pg/mL vs. 55.06 pg/mL ± 9.83 pg/mL, p < 0.0001) in yellow ligaments obtained from patients of the study group compared to control samples. The study did not establish a significant correlation between TGF-ß-1-3 concentrations and pain severity. The findings suggest that molecular therapy aimed at restoring the normal expression pattern of TGF-ß-1-3 could be a promising strategy for treating degenerative stenosis of the L/S spine. The study underscores the potential therapeutic significance of addressing molecular changes at the TGF-ß isoforms level for better understanding and managing degenerative spinal conditions.

Radiological Analysis of Cerebrospinal Fluid Dynamics at the Craniovertebral Junction Using Time-Spatial Labeling Inversion Pulse Magnetic Resonance Imaging in Patients with Cervical Spinal Canal Stenosis.

OBJECTIVE: Spondylotic changes in the cervical spine cause degeneration, leading to cervical spinal canal stenosis. This stenotic change can affect cerebrospinal fluid (CSF) dynamics by compressing the dural sac and reducing space in the subarachnoid space. We examined CSF dynamics at the craniovertebral junction (CVJ) using time-spatial labeling inversion pulse magnetic resonance imaging (Time-SLIP MRI) in patients with cervical spinal canal stenosis. METHODS: The maximum longitudinal movement of the CSF at the CVJ was measured as length of motion (LOM) in the Time-SLIP MRI of 56 patients. The sum of ventral and dorsal LOM was defined as the total LOM. Patients were classified into 3 groups depending on their spinal sagittal magnetic resonance imaging findings: control (n = 27, Kang classification grades 0 and 1), stenosis (n = 14, Kang classification grade 2), and severe stenosis (n = 15, Kang classification grade 3). RESULTS: Time-SLIP MRI revealed pulsatile movement of the CSF at the CVJ. The mean total, ventral, and dorsal LOM was 14.2 ± 9, 8.1 ± 5.7, and 3.8 ± 2.9 mm, respectively. The ventral LOM was significantly larger than the dorsal LOM. The total LOM was significantly smaller in the severe stenosis group (6.1 ± 3.4 mm) than in the control (16.0 ± 8.4 mm) or stenosis (11 ± 5.4 mm) groups (P < 0.001, Kruskal-Wallis H-test). In 5 patients, postoperative total LOM was improved after adequate decompression surgery. CONCLUSIONS: This study demonstrates that CSF dynamics at the CVJ are influenced by cervical spinal canal stenosis. Time-SLIP MRI is useful for evaluating CSF dynamics at the CVJ in patients with spinal canal stenosis.

Quantitative evaluation of the lumbar ligamentum flavum using MRI T2-mapping: Efficacy of its clinical application in patients with lumbar spinal stenosis.

OBEJECTIVE: To perform a magnetic resonance imaging T2-mapping of the ligamentum flavum in healthy individuals and patients with lumbar spinal stenosis scheduled for surgery and compare the T2 relaxation times. SUBJECTS AND METHODS: The T2 relaxation time of the ligamentum flavum was compared among 3 groups, healthy young individuals (H group (age< 50)), healthy middle-aged and older individuals (H group (age≥50)), and patients with lumbar spinal stenosis (L group). Additionally, the thickness of the ligament was measured in the axial image plane, and the occupied area ratio of each fiber was measured by staining the surgically obtained ligament, and each was correlated with the T2 relaxation time. We also evaluated the adhesion of the ligamentum flavum with the dura mater during the surgery. RESULTS: The T2 relaxation times were significantly prolonged in H group (age ≥50) and L group (P < 0.001) compared to H group (age<50). The relationship between collagen fiber and T2 relaxation times was significantly positive (r = 0.720, P < 0.001). Moreover, the relaxation times were significantly prolonged in those with adhesion of the ligamentum flavum with the dura mater (P < 0.05). The cut-off for the relaxation time was 50 ms (sensitivity: 62.50%, false positive rate: 10.8%). CONCLUSION: Healthy middle-aged and older individuals and patients with lumbar spinal stenosis and adhesion of the ligamentum flavum with the dura mater have prolonged T2 relaxation times. Hence, the adhesion between the ligamentum flavum and dura mater should be considered in cases with a relaxation time ≥50 ms.

A Convolutional Neural Network for Automated Detection of Cervical Ossification of the Posterior Longitudinal Ligament using Magnetic Resonance Imaging.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: We aimed to develop and validate a convolutional neural network (CNN) model to distinguish between cervical ossification of posterior longitudinal ligament (OPLL) and multilevel degenerative spinal stenosis using Magnetic Resonance Imaging (MRI) and to compare the diagnostic ability with spine surgeons. SUMMARY OF BACKGROUND DATA: Some artificial intelligence models have been applied in spinal image analysis and many of promising results were obtained; however, there was still no study attempted to develop a deep learning model in detecting cervical OPLL using MRI images. MATERIALS AND METHODS: In this retrospective study, 272 cervical OPLL and 412 degenerative patients underwent surgical treatment were enrolled and divided into the training (513 cases) and test dataset (171 cases). CNN models applying ResNet architecture with 34, 50, and 101 layers of residual blocks were constructed and trained with the sagittal MRI images from the training dataset. To evaluate the performance of CNN, the receiver operating characteristic curves of 3 ResNet models were plotted and the area under the curve were calculated on the test dataset. The accuracy, sensitivity, and specificity of the diagnosis by the CNN were calculated and compared with 3 senior spine surgeons. RESULTS: The diagnostic accuracies of our ResNet34, ResNet50, and ResNet101 models were 92.98%, 95.32%, and 97.66%, respectively; the area under the curve of receiver operating characteristic curves of these models were 0.914, 0.942, and 0.971, respectively. The accuracies and specificities of ResNet50 and ResNet101 models were significantly higher than all spine surgeons; for the sensitivity, ResNet101 model achieved better values than that of the 2 surgeons. CONCLUSION: The performance of our ResNet model in differentiating cervical OPLL from degenerative spinal stenosis using MRI is promising, better results were achieved with more layers of residual blocks applied.

Manipulation of osteogenic and adipogenic differentiation of human degenerative disc and ligamentum flavum derived progenitor cells using IL-1ß, IL-19, and IL-20.

PURPOSE: To elucidate whether pro-inflammatory cytokines might influence the commitment of intervertebral disc (IVD)- and ligamentum flavum (LF)-derived progenitor cells toward either osteogenesis or adipogenesis, specifically Interleukin-1ß (IL-1ß), IL-19, and IL-20. METHODS: Sixty patients with degenerative spondylolisthesis and lumbar or lumbosacral spinal stenosis were included in the study. Injuries to the spine, infections, and benign or malignant tumors were excluded. From nine patient samples, IVD- and LF-derived cells were isolated after primary culture, and two clinical samples were excluded due to mycoplasma infection. The effects of IL-1ß, IL-19, as well as IL-20 in regulating osteogenic and adipogenic differentiation in vitro were investigated. RESULTS: Primary IVD- and LF-derived cells were found to have a similar cell morphology and profile of surface markers (CD44, CD90, and CD105) as placenta-derived mesenchymal stem cells (MSCs). Primary IVD/LF cells have a high capacity to differentiate into osteocytes and adipocytes. IL-19 had a tendency to promote adipogenesis. IL-20 inhibited osteogenesis and promoted adipogenesis; IL-1ß promoted osteogenesis but inhibited adipogenesis. CONCLUSION: IL-1ß, IL-19, and IL-20 impact the adipogenic and osteogenic differentiation of IVD-derived and LF-derived cells. Modulating the expression of IL-1ß, IL-19, and IL-20 provides a potential avenue for controlling cell differentiation of IVD- and LF-derived cells, which might have beneficial effect for degenerative spondylolisthesis and spinal stenosis.

Transcriptomic alterations in hypertrophy of the ligamentum flavum: interactions of Rho GTPases, RTK, PIK3, and FGF.

PURPOSE: To analyze the differential transcriptome expression in hypertrophic ligaments flavum (HLF) compared to normal ligaments. METHODS: A case-control study was conducted that included 15 patients with hypertrophy of LF and 15 controls. Samples of LF were obtained through a lumbar laminectomy and analyzed by DNA microarrays and histology. The dysregulated biological processes, signaling pathways, and pathological markers in the HLF were identified using bioinformatics tools. RESULTS: The HLF had notable histological alterations, including hyalinosis, leukocyte infiltration, and disarrangement of collagen fibers. Transcriptomic analysis showed that up-regulated genes were associated with the signaling pathways of Rho GTPases, receptor tyrosine kinases (RTK), fibroblast growth factors (FGF), WNT, vascular endothelial growth factor, phosphoinositide 3-kinase (PIK3), mitogen-activated protein kinases, and immune system. The genes PIK3R1, RHOA, RPS27A, CDC42, VAV1, and FGF5, 9, 18, and 19 were highlighted as crucial markers in HLF. The down-expressed genes in the HLF had associations with the metabolism of RNA and proteins. CONCLUSION: Our results suggest that abnormal processes in hypertrophied LF are mediated by the interaction of the Rho GTPase, RTK, and PI3K pathways, which have not been previously described in the HLF, but for which there are currently therapeutic proposals. More studies are required to confirm the therapeutic potential of the pathways and mediators described in our results.

Postoperative Dural Sac Cross-Sectional Area as an Association for Outcome After Surgery for Lumbar Spinal Stenosis: Clinical and Radiological Results From the NORDSTEN-Spinal Stenosis Trial.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: The aim was to investigate the association between postoperative dural sac cross-sectional area (DSCA) after decompressive surgery for lumbar spinal stenosis and clinical outcome. Furthermore, to investigate if there is a minimum threshold for how extensive a posterior decompression needs to be to achieve a satisfactory clinical result. SUMMARY OF BACKGROUND DATA: There is limited scientific evidence for how extensive lumbar decompression needs to be to obtain a good clinical outcome in patients with symptomatic lumbar spinal stenosis. MATERIALS AND METHODS: All patients were included in the Spinal Stenosis Trial of the NORwegian Degenerative spondylolisthesis and spinal STENosis (NORDSTEN)-study. The patients underwent decompression according to three different methods. DSCA measured on lumbar magnetic resonance imaging at baseline and at three months follow-up, and patient-reported outcome at baseline and at two-year follow-up were registered in a total of 393 patients. Mean age was 68 (SD: 8.3), proportion of males were 204/393 (52%), proportion of smokers were 80/393 (20%), and mean body mass index was 27.8 (SD: 4.2).The cohort was divided into quintiles based on the achieved DSCA postoperatively, the numeric, and relative increase of DSCA, and the association between the increase in DSCA and clinical outcome were evaluated. RESULTS: At baseline, the mean DSCA in the whole cohort was 51.1 mm 2 (SD: 21.1). Postoperatively the area increased to a mean area of 120.6 mm 2 (SD: 46.9). The change in Oswestry disability index in the quintile with the largest DSCA was -22.0 (95% CI: -25.6 to -18), and in the quintile with the lowest DSCA the Oswestry disability index change was -18.9 (95% CI: -22.4 to -15.3). There were only minor differences in clinical improvement for patients in the different DSCA quintiles. CONCLUSION: Less aggressive decompression performed similarly to wider decompression across multiple different patient-reported outcome measures at two years following surgery.

[Rare complication of echinococcosis in clinical practice]. / Redkoe oslozhnenie ekhinokokkoza.

The authors report retroperitoneal echinococcosis with destruction of the bodies and left transverse processes of L4-5 vertebrae, recurrence and pathological fracture of L4-5 vertebrae with secondary spinal stenosis and left-sided monoparesis. Retroperitoneal echinococcectomy, pericystectomy, decompressive laminectomy L5 and foraminotomy L5-S1 on the left were performed. Therapy with albendazole was prescribed in postoperative period.

Generalization of a clinical diagnosis support tool for lumbar spinal stenosis: Can the ankle brachial pressure index be replaced by palpation of the posterior tibial artery in the lumbar spinal stenosis diagnostic support tool? (DISTO project).

BACKGROUND: The Japanese Society for Spine Surgery and Related Research previously developed a diagnostic support tool for lumbar spinal stenosis (LSS-DST). Using the LSS-DST, general physicians can identify potential cases of LSS. However, in the LSS-DST, measurement of the ankle brachial pressure index (ABI) is required to exclude peripheral artery lesions in the lower limbs. We can expect further application of the LSS-DST if we can identify a simpler and easier method than ABI measurement. Therefore, in this large-scale, multicenter, cross-sectional study, we verified whether palpation of the posterior tibial (PT) artery could be used instead of ABI in the LSS-DST. METHODS: This survey was conducted at 2177 hospitals and included 28,883 participants. The sensitivity and specificity of the original LSS-DST method using the ABI and that of the LSS-DST ver2.0 with PT artery palpation were assessed to screen their ability for diagnosing LSS, using the physicians' final diagnosis based on the patients' history, physical examination and radiographic findings as the gold standard. RESULTS: The sensitivity and specificity [95%CI] of the LSS-DST were 88.2% [87.5, 88.8] and 83.9% [83.4, 84.5], respectively, whereas the sensitivity and specificity of the LSS-DST ver2.0 were 87.7% [87.0, 88.3] and 78.3% [77.7, 78.9], respectively, indicating that LSS-DST ver2.0 is a useful screening tool for LSS with good sensitivity. CONCLUSION: When the item of ABI in the LSS-DST is replaced by palpation of the PT artery (LSS-DST ver2.0), its sensitivity is maintained as a screening tool for LSS. LEVEL OF EVIDENCE: Level 3.

Impact of oxidized LDL/LOX-1 system on ligamentum flavum hypertrophy.

BACKGROUND: Patients with lumbar spinal canal stenosis (LSS) often have peripheral arterial disease and aortic disease based on atherosclerosis. Oxidized LDL, which is clinically involved in the development of atherosclerosis, may also influence LF hypertrophy, but the function of the oxidized low-density lipoprotein (LDL)/lectin-type oxidized LDL receptor 1 (LOX-1) system in LF hypertrophy is unknown. We aimed to elucidate the potential involvement of oxidized LDL/LOX-1 system in ligamentum flavum (LF) hypertrophy. METHODS: A total of 43 samples were collected from LF tissues of the patients who underwent posterior lumbar spinal surgery. Immunohistochemistry for LOX-1 was performed using human LF samples. We treated the cells in vitro with inflammatory cytokines TNF-α and IL-1ß, oxidized LDL, and simvastatin. The expressions of LOX-1 and LF hypertrophy markers including type I collagen, Type III collagen, and COX-2 were assessed by real-time RT-PCR and immunocytochemistry. Phosphorylation of MAPKs and NF-κb was evaluated by Western blot after treatment with TNF-α, IL-1ß, oxidized LDL, and simvastatin. RESULTS: A significant weak correlation was observed between the number of positive cells of LOX-1 and cross-sectional area of LF on preoperative axial magnetic resonance imaging. In functional analysis, simvastatin treatment neutralized the oxidized LDL-mediated induction of mRNA expressions of LF hypertrophy markers. Western blot analysis showed that oxidized LDL as well as TNF-α and IL-1ß activated the signaling of MAPKs and NF-κb in LF cells, and that simvastatin treatment reduced the phosphorylation of all signaling. The TNF-α and IL-1ß treatments increased both mRNA and protein expression of LOX-1 in LF cells. CONCLUSION: We found a link between the oxidized LDL/LOX-1 system and LF hypertrophy. In addition, our in vitro analysis indicate that oxidized LDL may affect LF hypertrophy through signaling of MAPKs. Our results suggest that the oxidized LDL/LOX-1 system may be a potential therapeutic target for LSS.

Spinal Cord Sarcoidosis Occurring at Sites of Spondylotic Stenosis, Mimicking Spondylotic Myelopathy: A Case Series and Review of the Literature.

Sarcoidosis is a multisystem granulomatous disease, with intramedullary spinal cord involvement seen in <1% of cases. This case series illustrates the clinical presentations and imaging findings of 5 patients with intramedullary spinal neurosarcoidosis occurring at sites of spondylotic spinal canal stenosis, which can be indistinguishable from spondylotic myelopathy with cord enhancement. Both entities are most common in middle-aged men and present with weeks to months of motor and sensory symptoms. On imaging, both can have focal spinal cord enhancement and longitudinally extensive signal abnormality centered at or just below the level of spinal canal stenosis. On the basis of our experience, we suggest that in patients with cord enhancement centered at or just below a site of spinal canal stenosis, consideration should be given to chest imaging and lymph node biopsy when applicable, to assess for the possibility of underlying sarcoidosis before surgical decompression.

Redundant nerve roots indicate higher degree of stenosis in lumbar spine stenotic patients.

OBJECTIVES: Redundant Nerve Root (RNR) is a tortuous and elongated radiological appearance of cauda equina on Magnetic Resonance Imaging (MRI) in Lumbar Spinal Canal Stenosis (LSCS) patients. This study evaluated preoperative spinal morphometry associated with the development of RNR. METHODS: The retrospective cohort was conducted at The Aga Khan University Hospital, and included patients undergoing decompressive spinal surgery secondary to degenerative LSCS in 2015. The patients were divided into two groups with respect to the presence of preoperative RNR. Spinal morphometry was defined by several radiological parameters, including areas of dural sac (DSA), spinal canal, spinal foramen, facets, and spinal joints, and bilateral angles based on vertebral anatomy. RESULTS: A total of 55 patients were enrolled with a mean age of 57.1 years, in which 22 (40%) expressed RNR in their MRI. The RNR group had significantly lower mean DSA (59.64 vs 84.01 mm2; p = 0.028), bilateral posterior facet angle (Right: 33.84 vs 46.21, p = 0.004; Left: 36.43 vs 43.80, p = 0.039) and higher bilateral anterior facet angles (Right: 54.85 vs 44.57, p = 0.026; Left: 55.27 vs 46.36, p = 0.050) compared to the non-RNR group. The other bidimensional and angular parameters did not observe any statistical difference between the two groups. CONCLUSION: RNR was associated with a higher degree of stenosis in patients with LSCS. Bilateral anterior and posterior facets angles contribute to its development, indicating particular spinal morphology to be vulnerable to the stenotic disease.

Molecular and Genetic Mechanisms of Spinal Stenosis Formation: Systematic Review.

Spinal stenosis (SS) is a multifactorial polyetiological condition characterized by the narrowing of the spinal canal. This condition is a common source of pain among people over 50 years old. We perform a systematic review of molecular and genetic mechanisms that cause SS. The five main mechanisms of SS were found to be ossification of the posterior longitudinal ligament (OPLL), hypertrophy and ossification of the ligamentum flavum (HLF/OLF), facet joint (FJ) osteoarthritis, herniation of the intervertebral disc (IVD), and achondroplasia. FJ osteoarthritis, OPLL, and HLF/OLFLF/OLF have all been associated with an over-abundance of transforming growth factor beta and genes related to this phenomenon. OPLL has also been associated with increased bone morphogenetic protein 2. FJ osteoarthritis is additionally associated with Wnt/ß-catenin signaling and genes. IVD herniation is associated with collagen type I alpha 1 and 2 gene mutations and subsequent protein dysregulation. Finally, achondroplasia is associated with fibroblast growth factor receptor 3 gene mutations and fibroblast growth factor signaling. Although most publications lack data on a direct relationship between the mutation and SS formation, it is clear that genetics has a direct impact on the formation of any pathology, including SS. Further studies are necessary to understand the genetic and molecular changes associated with SS.

EGF Contributes to Hypertrophy of Human Ligamentum Flavum via the TGF-ß1/Smad3 Signaling Pathway.

Background: The most common spinal disorder in elderly is lumbar spinal canal stenosis (LSCS). Previous studies showed that ligamentum flavum hypertrophy (LFH) with fibrosis as the main pathological change is one of the pathogenic factors leading to LSCS. Epidermal Growth Factor (EGF) is known to have an intimate relationship with fibrosis in various tissues. Nevertheless, currently, there are few studies regarding EGF in LFH. The effect of EGF on the development of LFH is unknown, and the underlying pathomechanism remains unclear. In this study, we investigated the role of EGF in LFH and its potential molecular mechanism. Methods: First, the expression levels of EGF, phosphorylation of EGF receptor (pEGFR), Transforming growth factor-ß1 (TGF-ß1), Phosphorylated Smad3 (pSmad3), collagen I and collagen III were examined via immunohistochemistry and Western blot in LF tissues from patients with LSCS or Non-LSCS. Second, primary LF cells were isolated from adults with normal LF thickness and were cultured with different concentrations of exogenous EGF with or without erlotinib/TGF-ß1-neutralizing antibody. Results: The results showed that EGF, pEGFR, TGF-ß1, pSmad3, collagen I and collagen III protein expression in the LSCS group was significantly higher than that in the Non-LSCS group. Meanwhile, pEGFR, TGF-ß1, pSmad3, collagen I and collagen III protein expression was significantly enhanced in LF cells after exogenous EGF exposure, which can be notably blocked by erlotinib. In addition, pSmad3, collagen I and collagen III protein expression was blocked by TGF-ß1-neutralizing antibody. Conclusions: EGF promotes the synthesis of collagen I and collagen III via the TGF-ß1/Smad3 signaling pathway, which eventually contributes to LFH.

Efficacy of Spinous Process Splitting Decompression Compared with Conventional Laminectomy for Degenerative Lumbar Stenosis.

BACKGROUND: Spinous process splitting decompression (SPSD) is a minimally invasive surgical technique. We evaluated the clinical and radiological outcomes of SPSD compared with conventional laminectomy for the treatment of degenerative lumbar spinal stenosis. METHODS: SPSD was performed in 144 patients (group 1) and conventional laminectomy was performed in 132 patients (group 2) for degenerative lumbar spinal stenosis. Operative time, blood loss, hospital stay, and complications were compared between groups. Functional outcome was evaluated 2 years after surgery by Oswestry Disability Index, visual analog scale for back pain and leg pain, and progress in walking capacity. Spinal anteroposterior diameter and cross-sectional area were assessed by magnetic resonance imaging and computed tomography. RESULTS: Both groups showed significant improvement in mean functional outcome scores of Oswestry Disability Index and mean visual analog scale for back and leg pain after surgery (P < 0.001), although the differences in scores between the groups (P > 0.05) were not statistically significant. Walking capacity was reported as "much better" and "moderately better" in 89% of patients in group 1 and 87.8% of patients in group 2 (P > 0.05). On the basis of radiographic findings, satisfactory neurological decompression was achieved in group 1 (72.2% increase in mean spinal anteroposterior diameter, 102.5% increase in cross-sectional area) and group 2 (80.3% in mean spinal anteroposterior diameter, 108.8% increase in cross-sectional area) (P > 0.05). CONCLUSIONS: Patients who underwent SPSD for lumbar spinal decompression had comparable functional recovery rates correlated with clinical and radiological improvement to patients who underwent conventional laminectomy.

Probability for surgical treatment in patients with lumbar spinal stenosis according to the stenotic lesion severity: a 5-10-year follow-up study.

BACKGROUND: We aimed (1) to clarify difference in the natural history of lumbar spinal stenosis (LSS) with respect to surgical treatment according to severity of stenosis on magnetic resonance imaging (MRI) using qualitative grading system and (2) to estimate surgical probabilities depending on radiological severity. METHODS: With the design of retrospective observational study, a total of 1,248 patients diagnosed with LSS between 2011 and 2014 at our hospital were followed up for the mean duration of 7.7 years (5.17-9.8 years). We investigated severity of central and foraminal stenoses on initial MRI using qualitative grading system and whether surgical treatment was performed. Logistic regression models were used to identify risk factors for surgery. RESULTS: During the mean follow-up period of 7.7 years, grade 3 maximal central stenosis showed the highest percentage of surgical treatment (57.9%-62.3%) with no significant difference in surgical probabilities according to concomitant foraminal stenosis. Surgical probabilities in grade 2 and 3 maximal foraminal stenosis, were 22.2%-62.3% and 33.3%-57.9%, respectively, depending on concomitant central stenosis. Maximal central stenosis of grades 1, 2, and 3 (odds ratio [OR]: 1.79, 2.21, and 6.26, respectively), and maximal foraminal stenosis of grades 2 and 3 (OR: 2.22 and 2.12, respectively) were significant risk factors for surgical treatment. CONCLUSIONS: The high grades of maximal central and foraminal stenoses were risk factors for surgical treatment. Surgical probabilities were 57.9%-62.3% in grade 3 maximal central stenosis, 22.2%-62.3% and 33.3%-57.9%, respectively, in grade 2 and 3 maximal foraminal stenosis during the mean follow-up period of 7.7 years. These results indicate that the natural history of LSS differs according to grade of maximal central and foraminal stenoses.

The Relationship Between Wild-Type Transthyretin Amyloid Load and Ligamentum Flavum Thickness in Lumbar Stenosis Patients.

BACKGROUND: One key contributor to lumbar stenosis is thickening of the ligamentum flavum (LF), a process still poorly understood. Wild-type transthyretin amyloid (ATTRwt) has been found in the LF of patients undergoing decompression surgery, suggesting that amyloid may play a role. However, it is unclear whether within patients harboring ATTRwt, the amount of amyloid is associated with LF thickness. METHODS: From an initial cohort of 324 consecutive lumbar stenosis patients whose LF specimens from decompression surgery were sent for analysis (2018-2019), 33 patients met the following criteria: 1) Congo red-positive amyloid in the LF, 2) ATTRwt by mass spectrometry-based proteomics, and 3) an available preoperative magnetic resonance imaging. Histological specimens were digitized, and amyloid load was quantified through Trainable Weka Segmentation machine learning. LF thicknesses were manually measured on axial T2-weighted preoperative magnetic resonance imaging scans at each lumbar level, L1-S1. The sum of thicknesses at every lumbar LF level (L1-S1) equals "lumbar LF burden". RESULTS: Patients had a mean age of 72.7 years (range = 59-87), were mostly male (61%) and white (82%), and predominantly had surgery at L4-L5 levels (73%). Amyloid load was positively correlated with LF thickness (R = 0.345, P = 0.0492) at the levels of surgical decompression. Furthermore, amyloid load was positively correlated with lumbar LF burden (R = 0.383, P = 0.0279). CONCLUSIONS: Amyloid load is positively correlated with LF thickness and lumbar LF burden across all lumbar levels, in a dose-dependent manner. Further studies are needed to validate these findings, uncover the underlying pathophysiology, and pave the way toward using therapies that slow LF thickening.

The Utility of Flexion-Extension Radiographs in Degenerative Cervical Spondylolisthesis.

STUDY DESIGN: Retrospective radiologic analysis. OBJECTIVE: The aim was to investigate if lateral flexion-extension radiographs identify additional cases of degenerative cervical spondylolisthesis (DCS) that would be missed by obtaining solely neutral upright radiographs, and determine the reliability of magnetic resonance imaging (MRI) in diagnosis. SUMMARY OF BACKGROUND DATA: DCS and instability can be a cause of neck pain, radiculopathy, and even myelopathy. Standard anteroposterior and lateral radiographs and MRI of the cervical spine will identify most cervical spine pathology, but spondylolisthesis and instability are dynamic issues. Standard imaging may also miss DCS in some cases. METHODS: We compared the number of patients who demonstrated cervical spondylolisthesis on lateral neutral and flexion-extension radiographs in addition to MRI. We used established criteria to define instability as ≥2 mm of listhesis on neutral imaging, and ≥1 mm of motion between flexion-extension radiographs. RESULTS: A total of 111 patients (555 cervical levels) were analyzed. In all, 41 patients (36.9%) demonstrated cervical spondylolisthesis on neutral and/or flexion-extension radiographs. Of the 77 levels of spondylolisthesis, 17 (22.1%) were missed on neutral radiographs ( P ,0.05). Twenty levels (26.0%) were missed when flexion-extension radiographs were used alone ( P =0.02). Twenty-nine levels (37.7%) of DCS identified on radiograph were missed by MRI ( P =0.004). CONCLUSIONS: Lateral flexion-extension views can be useful in the diagnosis of DCS. These views provide value by identifying a significant cohort of patients that would be undiagnosed based on neutral radiographs alone. Moreover, MRI missed 38% of DCS cases identified by radiographs. Therefore, lateral radiographs can be a useful adjunct to neutral radiographs and MRI when instability is suspected or if these imaging modalities are unable to identify the source of a patient's neck or arm pain.

Association between depression and anxiety on symptom and function after surgery for lumbar spinal stenosis.

Evidence on the role of depression and anxiety in patients undergoing surgical treatment for symptomatic degenerative lumbar spinal stenosis (DLSS) is conflicting. We aimed to assess the association between depression and anxiety with symptoms and function in patients undergoing surgery for DLSS. Included were patients with symptomatic DLSS participating in a prospective multicentre cohort study who underwent surgery and completed the 24-month follow-up. We used the hospital anxiety and depression scale (HADS) to assess depression/anxiety. We used mixed-effects models to quantify the impact on the primary outcome change in the spinal stenosis measure (SSM) symptoms/function subscale from baseline to 12- and 24-months. Logistic regression analysis was used to quantify the odds of the SSM to reach a minimal clinically important difference (MCID) at 24 months follow-up. The robustness of the results in the presence of unmeasured confounding was quantified using a benchmarking method based on a multiple linear model. Out of 401 patients 72 (17.95%) were depressed and 80 anxious (19.05%). Depression was associated with more symptoms (ß = 0.36, 95% confidence interval (CI) 0.20 to 0.51, p < 0.001) and worse function (ß = 0.37, 95% CI 0.24 to 0.50, p < 0.001) at 12- and 24-months. Only the association between baseline depression and SSM symptoms/function was robust at 12 and 24 months. There was no evidence for baseline depression/anxiety decreasing odds for a MCID in SSM symptoms and function over time. In patients undergoing surgery for symptomatic DLSS, preoperative depression but not anxiety was associated with more severe symptoms and disability at 12 and 24 months.

Is radiographic lumbar spinal stenosis associated with the quality of life?: The Wakayama Spine Study.

OBJECTIVES: This prospective study aimed to determine the association between radiographic lumbar spinal stenosis (LSS) and the quality of life (QOL) in the general Japanese population. METHODS: The severity of radiographic LSS was qualitatively graded on axial magnetic resonance images as follows: no stenosis, mild stenosis with ≤1/3 narrowing, moderate stenosis with a narrowing between 1/3 and 2/3, and severe stenosis with > 2/3 narrowing. Patients less than 40 years of age and those who had undergone previous lumbar spine surgery were excluded from the study. The Oswestry Disability Index (ODI), which includes 10 sections, was used to assess the QOL. One-way analysis of variance was performed to determine the statistical relationship between radiographic LSS and ODI. Further, logistic regression analysis adjusted for gender, age, and body mass index was performed to detect the relationship. RESULTS: Complete data were available for 907 patients (300 men and 607 women; mean age, 67.3±12.4 years). The prevalence of severe, moderate, and non-mild/non-radiographic were 30%, 48%, and 22%, respectively. In addition, the mean values of ODI in each group were 12.9%, 13.1%, and 11.7%, respectively, and there was no statistically significant difference between the three groups in logistic analysis (P = 0.55). In addition, no significant differences in any section of the ODI were observed among the groups. However, severe radiographic LSS was associated with low back pain in the "severe" group as determined by logistic analysis adjusted for gender, age, and body mass index (odds ratio: 1.53, confidence interval: 1.13-2.07) compared with the non-severe group. CONCLUSION: In this general population study, severe radiographic LSS was associated with low back pain (LBP), but did not affect ODI.