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.

Multilevel calcium pyrophosphate dihydrate deposition in cervical ligamentum flavum: clinical characteristics and imaging features

Background Involvement in cervical ligamentum flavum is a rare manifestation of the calcium pyrophosphate dihydrate deposition disease. Only few cases of this condition have been reported. We revealed eighteen cases of CPPD in cervical ligamentum flavum that diagnosed at a single medical center. In our case series, clinical characteristics and magnetic resonance imaging findings of patients are described. Methods We retrospectively reviewed the medical charts and imaging studies of the eighteen patients with pseudogout attack of the cervical ligamentum flavum. In addition, we discussed the differences between this disease and ossification of ligamentum flavum in image manifestations. Results There were fourteen men and four women aged between 59 and 87 years. Diabetes mellitus and hypertension were the most common comorbidities. Myelopathy and neck pain were presented in most patients. C4–5 and C5–6 were attacked most frequently, and multiple- rather than single-level involvement could be observed in our series. “Acute on chronic phenomenon” was a specific magnetic resonance image finding in patients whose symptom durations were between 2 to 5 months. Compared to ossification of ligamentum flavum, calcium pyrophosphate dihydrate crystal deposition had different image signs, including morphology, side of the involved ligament, no continuity with the lamina, acute on chronic phenomenon, and presence of retro-odontoid mass. Conclusions Nodular calcifications in cervical ligamentum flavum raise highly suspicion for calcium pyrophosphate dihydrate deposition and must be diagnosed by histological examination and polarized light microscopy. This disease is different from ossification of ligamentum flavum, and it could be recognized by specific image features.

Deciphering Expression Profiling and Functional Signatures of Individualized Obesity-Associated Genes in Ossification of Ligamentum Flavum Through RNA-Sequence Data Mining

Background: Obese individuals predispose to ossification of ligamentum flavum (OLF), whereas the underlying connections between obesity phenotype and OLF pathomechanism are not fully understood, especially during early life. This study aimed to explore obesity-associated genes and their functional signatures in OLF. Methods: Gene microarray expression data related to OLF were downloaded from the GSE106253 dataset in the Gene Expression Omnibus (GEO) database. The potential obesity-related differentially expressed genes (ORDEGs) in OLF were screened. Then, gene-ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for these genes. Furthermore, protein-protein interactions (PPI) were used to identify hub ORDEGs, and Metascape was used to further verify the key signaling pathways and immune-related function signatures of hub ORDEGs. Finally, correlation analysis of hub ORDEGs and identified OLF-related infiltrating immune cells (OIICs) was constructed to understand the possible mechanical link among obesity, immune response and OLF. Results: OLF-related differentially expressed genes and 2051 obesity-related genes from four databases were intersected to obtain 99 ORDEGs, including 54 upregulated and 55 downregulated genes. GO and KEGG analysis revealed that these genes were mainly involved in metabolism, inflammation and immune-related biological functions and pathways. A PPI network was established to determine 14 hub genes (AKT1, CCL2, CCL5, CXCL2, ICAM1, IL10, MYC, PTGS2, SAA1, SOCS1, SOCS3, STAT3, TNFRSF1B and VEGFA). The co-expression network demonstrated that this module was associated with cellular response to biotic stimulus, regulation of inflammatory response, regulation of tyrosine phosphorylation of STAT protein. Furthermore, Metascape functional annotations showed that hub genes were mainly involved in receptor signaling pathway via JAK-STAT, response to TNF and regulation of defense response, and their representative enriched pathways were TNF, adipocytokine and JAK-STAT signaling pathways. Subgroup analysis indicated that T cell activation might be potential immune function processes involved, and correlation analysis revealed that cDCs, memory B-cells and preadipocytes were highly correlated infiltrating immune cells. Conclusions: Our study deciphered individualized obesity-associated gene signature for the first time, which may facilitate exploring the underlying cellular and molecular pathogenesis and novel therapeutic targets of obesity-related early-onset OLF.

The role of cerebrospinal fluid cross-section area ratio in the prediction of dural ossification and clinical outcomes in patients with thoracic ossification of ligamentum flavum

Background It is imperative to preoperatively distinguish dural ossification (DO) and thus anticipate the risks and outcome of the surgery for patients with ossification of ligamentum flavum (OLF). However, studies have disagreed as to the efficacy of the radiographic signs or factors to predict DO and surgical outcome. In additon, the association between the cerebrospinal fluid cross-section area ratio (CCAR) and DO or clinical outcome had not been reported. The purpose of this study was to analyse CCAR and its role in prediction of DO and neurological function recovery rate in patients with OLF. Methods Fifty-two consecutive patients with OLF, who underwent posterior thoracic decompression and fusion between September 2012 and March 2019 at a single institution, were retrospectively reviewed. Demographic data, radiographic signs of DO, CCAR, pre- and postoperative modified Japanese Orthopedic Association (mJOA) score were recorded. Results There were 27 patients in the DO group and 25 patients in the non-DO group, with a mean age at surgery of 57.4 years and 53.9 years, respectively. No significant differences were found in sex, age, segment of maximum compression and preoperative mJOA score between the two groups. The receiver operating characteristic curve showed that the value of CCAR had a relatively high value for diagnosis of DO and prediction of neurological function recovery rate (P = .000). According to the value of CCAR, three zones were defined as DO zone (≤14.3%), non-DO zone (≥44.5%), and gray zone (14.3 to 44.5%). When the value of CCAR≤14.3%, the recovery rate was poor or fair, while it had good or excellent recovery when CCAR≥45.2%. Conclusion The value of CCAR had a high diagnostic value for prediction of DO and neurological function recovery rate in patients with OLF.

The Role of Cerebrospinal Fluid Cross-Section Area Ratio in the Prediction of Dural Ossification and Clinical Outcomes in Patients with Thoracic Ossification of Ligamentum Flavum

Background: It is imperative to preoperatively distinguish dural ossification (DO) and thus anticipate the risks and outcome of the surgery for patients with ossification of ligamentum flavum (OLF). However, studies have disagreed as to the efficacy of the radiographic signs or factors to predict DO and surgical outcome. In additon, the association between the cerebrospinal fluid cross-section area ratio (CCAR) and DO or clinical outcome had not been reported. The purpose of this study was to analyse CCAR and its role in prediction of DO and neurological function recovery rate in patients with OLF.Methods: Fifty-two consecutive patients with OLF, who underwent posterior thoracic decompression and fusion between September 2012 and March 2019 at a single institution, were retrospectively reviewed. Demographic data, radiographic signs of DO, CCAR, pre- and postoperative modified Japanese Orthopedic Association (mJOA) score were recorded. Results: There were 27 patients in the DO group and 25 patients in the non-DO group, with a mean age at surgery of 57.4 years and 53.9 years, respectively. No significant differences were found in sex, age, segment of maximum compression and preoperative mJOA score between the two groups. The receiver operating characteristic curve showed that the value of CCAR had a relatively high value for diagnosis of DO and prediction of neurological function recovery rate ( P=.000). According to the value of CCAR, three zones were defined as DO zone (≤14.3%), non-DO zone (≥44.5%), and gray zone (14.3% to 44.5%). When the value of CCAR≤14.3%, the recovery rate was poor or fair, while it had good or excellent recovery when CCAR≥45.2%.Conclusion: The value of CCAR had a high diagnostic value for prediction of DO and neurological function recovery rate in patients with OLF.

Dysregulation of MicroRNAs in Hypertrophy and Ossification of Ligamentum Flavum: New Advances, Challenges, and Potential Directions

Pathological changes in the ligamentum flavum (LF) can be defined as a process of chronic progressive aberrations in the nature and structure of ligamentous tissues characterized by increased thickness, reduced elasticity, local calcification, or aggravated ossification, which may cause severe myelopathy, radiculopathy, or both. Hypertrophy of ligamentum flavum (HLF) and ossification of ligamentum flavum (OLF) are clinically common entities. Though accumulated evidence has indicated both genetic and environmental factors could contribute to the initiation and progression of HLF/OLF, the definite pathogenesis remains fully unclear. MicroRNAs (miRNAs), one of the important epigenetic modifications, are short single-stranded RNA molecules that regulate protein-coding gene expression at posttranscriptional level, which can disclose the mechanism underlying diseases, identify valuable biomarkers, and explore potential therapeutic targets. Considering that miRNAs play a central role in regulating gene expression, we summarized current studies from the point of view of miRNA-related molecular regulation networks in HLF/OLF. Exploratory studies revealed a variety of miRNA expression profiles and identified a battery of upregulated and downregulated miRNAs in OLF/HLF patients through microarray datasets or transcriptome sequencing. Experimental studies validated the roles of specific miRNAs (e.g., miR-132-3p, miR-199b-5p in OLF, miR-155, and miR-21 in HLF) in regulating fibrosis or osteogenesis differentiation of LF cells and related target genes or molecular signaling pathways. Finally, we discussed the perspectives and challenges of miRNA-based molecular mechanism, diagnostic biomarkers, and therapeutic targets of HLF/OLF.