Unraveling a rare cause of spinal stenosis: Coexistent AL and ATTR amyloidosis involving the ligamentum flavum

Background: Amyloidosis is a protein misfolding disorder that leads to the deposition of beta-pleated sheets of a fibrillar derivative of various protein precursors. Identification of the type of precursor protein is integral in treatment decision-making. The presence of two different types of amyloid in the same patient is unusually rare, and there are no previous reports of two different types of amyloid deposition in the ligamentum flavum (LF) in the same patient. Case Description: Here, we describe two patients with spinal stenosis who underwent laminectomies and were found to have AL and ATTR amyloid deposits in the LF. Conclusion: As the spine is becoming recognized as a site for ATTRwt amyloid deposition, patients undergoing spinal decompression surgery may potentially benefit from evaluation for amyloidosis in the LF.

Activity of genes of matrix metalloproteinases and their inhibitors in the Ligamentum flavum of patients with stenosing processes in spinal canal and dural sac

New data have been obtained for assessing the expression of genes of metalloproteinases and their tissue inhibitors (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1 and TIMP-2) in the Ligamentum flavum in patients with lumbar stenosis of spinal canal and dural sac. The features of the metabolism of the extracellular matrix (ECM) were revealed, the data obtained were compared with those for previously studied candidate genes. The search for relationships with the features of the ECM metabolic characteristics was carried out.The aim. To study the expression of genes of metalloproteinases and their tissue inhibitors in intraoperative biopsies of the Ligamentum flavum of patients with lumbar stenosis of the spinal canal and dural sac.Materials and methods. A group of 33 people (17 women, 16 men) with lumbar stenosis of the spinal canal and dural sac was studied; the average age is 45.73 ± 1.95 years. RNA was isolated from intraoperative biopsies of the Ligamentum flavum, reverse transcription was performed, and PCR using specific primers was performed.Results. In Ligamentum flavum of patients with stenosing processes of the spinal canal and dural sac, an increased activity of MMP-1 and insufficient response of TIMP-1 and TIMP-2 were found; the expression of MMP-1 increased synchronously with Dio2, and both genes decreased their activity with increasing age of the patient. In patients with Ligamentum flavum ossification, the MMR-8 gene was more actively expressed, and the synthesis of the mRNA of the MMR-9 gene decreased compared to the subgroup without ossification.

Dissatisfaction Risk Factors of Patients after Laminectomy for Thoracic Ossification of Ligamentum Flavum: A Retrospective Cohort Study of Different Follow-Up Periods

Objectives. To explore the influencing factors of satisfaction with postoperative treatment in patients diagnosed with thoracic ossification of the ligamentum flavum during different follow-up periods. Methods. This was a retrospective study of 57 patients who were diagnosed with thoracic ossification of ligamentum flavum (TOLF) and treated with laminectomy in the Spine Surgery Department of the Third Hospital of Hebei Medical University from January 2010 to January 2017. The Patient Satisfaction Index (PSI) was collected at discharge and at 6-month, 1-year, and the last follow-up. According to the evaluation results, the patients could be divided into a satisfied group and a dissatisfied group. The patient’s Japanese Orthopaedic Association (JOA) score improvement rate was evaluated at the last follow-up. Possible influencing factors of the two groups of patients were compared and the related influencing factors of satisfaction with postoperative treatment in patients during different follow-up periods were summarized. Results. At the time of discharge, the dissatisfied and satisfied groups had significant differences in variables of diabetes mellitus, duration of preoperative symptoms, urination disorder, intramedullary signal change on MRI, dural ossification, residual rate of cross-sectional spinal canal area on CT, shape on the sagittal MRI, hospital stay, hospitalization expenses, postoperative pain in LE VAS, delayed wound healing, postoperative depression, and intercostal pain ( P < 0.05 ). There were also significant differences in urination disorder, postoperative pain according to the LE VAS, JOA score, and postoperative depression during the 6-month follow-up ( P < 0.05 ). There were no significant differences in other variables between the two groups ( P > 0.05 ). One year after the operation, there were significant differences between the dissatisfied group and the satisfied group in urination disorder, JOA score, and symptom recurrence ( P < 0.05 ). There were also significant differences in the JOA score and symptom recurrence at the final follow-up ( P < 0.05 ). For further analysis, the duration of preoperative symptoms in the satisfied group was less than 24 months and the duration of preoperative symptoms in the dissatisfied group was more than 24 months. The JOA scores of patients in the satisfied group and the dissatisfied group increased gradually with the improvement of neurological function in different follow-up periods, but, at the last follow-up, the JOA scores of patients in the satisfied group were significantly higher than those in the dissatisfied group. Conclusions. In conclusion, for thoracic ossification of ligamentum flavum patients who received laminectomy, dissatisfaction with the early and medium-term postoperative results may be related to diabetes, the duration of preoperative symptoms, hospitalization expenses, delayed wound healing, intercostal pain, and urination disorder, and dissatisfaction with the long-term postoperative results might be related to the low JOA score improvement rate and symptom recurrence.

Preoperative Magnetic Resonance Imaging Signal Intensity Classification Is Associated With Clinical Presentation and Surgical Outcomes in Myelopathy Caused by Thoracic Ossification of Ligamentum Flavum: A Multicenter Study

Study Design Retrospective Cohort Study Objectives To explore whether classification of the increased signal intensity (ISI) on magnetic resonance imaging (MRI) correlates with clinical presentations and outcomes in symptomatic thoracic ossification of ligamentum flavum (T-OLF) patients. Methods All patients with symptomatic T-OLF who underwent laminectomy at four institutions were reviewed. The ISI on preoperative T2-weighted MRI was divided into 3 groups, Grade 0, none; Grade 1, light (obscure); and Grade 2, intense (bright). Neurological function before surgery and at follow-up was evaluated by the revised Japanese Orthopedic Association (JOA) score. Patients’ demographics, clinical manifestations, and surgical outcomes were compared. Results A total of 94 patients were involved. Preoperative MRI showed 32 patients in Grade 0, 39 patients in Grade 1, and 23 patients in Grade 2. Low extremities numbness, weakness, and clinical signs were less frequent in Grade 0 patients. The grade of ISI was correlated with the duration of symptoms and cord compression. Grade 0 patients had a better preoperative JOA score than those with ISI changes, while Grade 2 patients showed worse neurological recovery, longer duration of operation, more intraoperative blood loss, and a higher incidence of perioperative complications. Conclusion The classification of ISI is an effective parameter for preoperatively assessing cord compression, clinical severity, and surgical outcomes in T-OLF patients. Grade 0 patients have relatively mild neurological impairment but are more likely to be misdiagnosed. Grade 2 indicates the worst clinical impairment and neurological recovery, and implies a risky and challenging surgery.

Anatomical features of the canine C2-C3 spinal cord vascular environment

OBJECTIVE Interarcuate branch (IAB) is a vascular structure, particularly developed in C2-3 intervertebral space, forming a dorsal bridge that connects ventral venous plexi in the vertebral canal. While precisely described in the human, the precise anatomical features of IABs have not been reported in the veterinary literature. The purpose of this study is to describe the features and relations of IABs in the C2-3 vertebral canal. ANIMALS 10 dogs were enrolled; 5 dogs for necropsy and 5 dogs for histology. PROCEDURES The ventral venous plexi in the cervical spine of 5 dogs were injected with latex and underwent vertebral canal dissection for visual assessment of the IAB. Two out of 5 dogs were injected with the addition of barium sulfate and underwent a CT scan. The C2-3 regions of 5 small-breed dogs were harvested for histological examinations. RESULTS IABs arose from the ventral venous plexus at the level of the intervertebral vein; they originated from 2 separate branches located caudally and cranially to the intervertebral foramen, forming a ventrodorsal triangle surrounding the spinal nerve root. No dorsal anastomosis was observed on the CT scan nor at dissection but were observed histologically. A cervical fibrous sheath was observed all around the vertebral canal. CLINICAL RELEVANCE IABs are voluminous venous structures at the C2-3 intervertebral space in dogs and found within a split of the cervical fibrous sheath, which is adherent to the interarcuate ligament and the ligamentum flavum. This anatomical description is paramount when planning an approach to the C2-3 intervertebral space.

Symptomatic thoracic ossification of the ligamentum flavum in a patient with ankylosing spondylitis: Report of a case and review

Background: Thoracic spinal cord compression due to both ankylosing spondylitis (AS) and ossification of the ligamentum flavum (OLF) is rare. Case Description: A 33-year-old male with AS presented with a paraparesis attributed to MR documented T9-T10 OLF/stenosis. He was successfully managed with a decompressive laminectomy; this resulted in marked improvement of his deficit. Conclusion: Thoracic OLF and AS rarely contribute T9-T10 spinal cord compression that may be readily relieved with a decompressive laminectomy.

Machine learning quantification of amyloid deposits in histological images of ligamentum flavum

ABSTRACTBackgroundWild-type transthyretin amyloidosis (ATTRwt) is an underdiagnosed and potentially fatal disease. Interestingly, ATTRwt deposits have been found to deposit in the ligamentum flavum (LF) of patients with lumbar spinal stenosis prior to the development of systemic and cardiac amyloidosis. In order to study this phenomenon and its possible relationship with LF thickening and systemic amyloidosis, a precise method of quantifying amyloid deposits in histological slides of LF is critical. However, such a method is currently unavailable. Here, we present a machine learning quantification method with Trainable Weka Segmentation (TWS) to assess amyloid deposition in histological slides of LF.MethodsImages of ligamentum flavum specimens stained with Congo red are obtained from spinal stenosis patients undergoing laminectomies and confirmed to be positive for ATTRwt. Amyloid deposits in these specimens are classified and quantified by TWS through training the algorithm via user-directed annotations on images of LF. TWS can also be automated through exposure to a set of training images with user-directed annotations, and then application to a set of new images without additional annotations. Additional methods of color thresholding and manual segmentation are also used on these images for comparison to TWS.ResultsWe develop the use of TWS in images of LF and demonstrate its potential for automated quantification. TWS is strongly correlated with manual segmentation in the training set of images with user-directed annotations (R = 0.98; p = 0.0033) as well as in the application set of images where TWS was automated (R = 0.94; p = 0.016). Color thresholding was weakly correlated with manual segmentation in the training set of images (R = 0.78; p = 0.12) and in the application set of images (R = 0.65; p = 0.23).ConclusionTWS machine learning closely correlates with the gold standard comparator of manual segmentation and outperforms the color thresholding method. This novel machine learning method to quantify amyloid deposition in histological slides of ligamentum flavum is a precise, objective, accessible, high throughput, and powerful tool that will hopefully pave the way towards future research and clinical applications.

Lumbar spinous process-splitting technique for ligamentum flavum cyst removal: the first use in Europe.

Background Laminotomy for lumbar stenosis is a well-defined procedure and represents a routine in every neurosurgical department. It is a common experience that the mono- or bilateral paraspinal muscles detachment together with supra and interspinous ligaments injury can lead to postoperative pain. In literature has been reported the application at the level of the lumbar spine of a minimally invasive technique defined as lumbar spinous process-splitting technique (LSPST). Methods In the current study, we present a case series of 12 patients that underwent LSPSL from September 2019 to April 2020. Two patient suffering from ligamentum flavum cyst, 8 patients with single level lumbar canal stenosis (LCS) and two patients with two-level LCS. The approach was mini-open, with reduced soft tissue dissection and without paraspinal muscles injury. Moreover, a novel morphological classification of postoperative muscle atrophy is proposed as well as a volumetric analysis of the decompression achieved. Conclusion At our knowledge, this is the first description of this surgical technique and the first LSPSL case series in Europe. Furthermore, cases of ligamentum flavum cyst removal using this safe and effective technique are not yet reported. Abbreviations Lumbar canal stenosis (LCS), lumbar spinous process-splitting technique (LSPST), minimally invasive spine surgery (MISS)

Mechanical Stress-Induced IGF-1 Facilitates col-I and col-III Synthesis via the IGF-1R/AKT/mTORC1 Signaling Pathway

Mechanical stress promotes human ligamentum flavum cells (LFCs) to synthesize multitype collagens, leading to ligamentum flavum hypertrophy (LFH). However, the mechanism of mechanical stress in the formation of collagen remains unclear. Therefore, we investigated the relationship between mechanical stress and collagen synthesis in the present study. First, LFCs were isolated from 9 patients and cultured with or without mechanical stress exposure for different times. IGF-1, collagen I (col-I), and collagen III (col-III) protein and mRNA levels were then detected via ELISA and qPCR, respectively. Moreover, the activation of pIGF-1R, pAKT, and pS6 was examined by Western blot analysis. To further explore the underlying mechanism, an IGF-1 neutralizing antibody, NVP-AEW541, and rapamycin were used. IGF-1, col-I, and col-III were significantly increased in stressed LFCs compared to nonstressed LFCs. In addition, the activation of pIGF-1R, pAKT, and pS6 was obviously enhanced in stressed LFCs. Interestingly, col-I protein, col-I mRNA, col-III protein, col-III mRNA, and IGF-1 protein, but not IGF-1 mRNA, were inhibited by IGF-1 neutralizing antibody. In addition, col-I and col-III protein and mRNA, but not IGF-1, were inhibited by both NVP-AEW541 and rapamycin. Moreover, the activation of pIGF-1R, pAKT, and pS6 was reduced by the IGF-1 neutralizing antibody and NVP-AEW541, and the activation of pS6 was reduced by rapamycin. In summary, these results suggested that mechanical stress promotes LFCs to produce IGF-1, which facilitates col-I and col-III synthesis via the IGF-1R/AKT/mTORC1 signaling pathway.