Clinical And Imaging Characteristics Of Lumbar Foraminal Stenosis And Study On The Regularity Of Traditional Chinese Medicine

Background:Lumbar radiculopathy is a clinically common degenerative disease of the lumbar spine.Among them,lumbar foraminal stenosis(LFS)is one of the main clinical diagnoses.LFS with radiculopathy is poorly recognized and easily missed and misdiagnosed due to its lack of specific clinical and imaging findings.Therefore,further exploration of the clinical and imaging features and their diagnostic value is integral to the etiological diagnosis and precision medicine of lumbar degenerative diseases.LFS often has an abnormal foraminal anatomy due to stenogenic factors and causes radicular symptoms in the lower extremities with compression of the spinal nerve root\dorsal root ganglia.The pathophysiology of dorsal root ganglion(DRG)compression injury and molecular mechanisms are clinically important in LFS with radiculopathy.Effective treatments are still lacking for radicular pain as peripheral neuropathic pain(NP).At present,the under diagnosis and low clinical efficacy of LFS have caused significant damage to the physical and mental health of patients and have caused a heavy burden on society.1.Correlation analysis of lumbar foraminal stenosis and clinical featuresObjective:In order to improve the level of etiological diagnosis of LFS,strengthen the awareness of traditional Chinese medicine(TCM)syndrome types and improve the efficiency of treatment,this study conducted an observational analysis of clinical symptoms,signs,and TCM Syndromes types of patients who had been clearly defined as LFS with radiculopathy,aiming to clarify the diagnostic basis of LFS and to develop a brief diagnostic tool that facilitates differentiation from other disorders.Methods:This retrospective analysis was conducted by using the clinical data obtained from 328 low back-related leg pain patients who underwent lumbar spine endoscopic surgery at the pain department of China Japan Friendship Hospital,between January 2015 to February 2020.The preoperative diagnosis was clarified based on preoperative diagnosis,surgical exploration,and postoperative effects,and the subjects were divided into LFS,LCS and LDH groups.The general data,symptoms,signs,preoperative NRS scores,preoperative JOA scores,and TCM syndrome types of the patients in the three groups were collected and collated for intergroup differences and correlation analysis.Results:(1)According to univariate logistic regression analysis,Kemp sign(+)and piriform muscle tension test(+)were significantly associated with LFS(P<0.01)in all patient groups.According to multivariate logistic regression analysis,Kemp sign(+)was found to be an independent influencing factor for the diagnosis of LFS(95%CI 1.579-10.773,P=0.004).Receiver operating characteristic(ROC)curve analysis based on Kemp's sign(+)for the diagnosis of LFS with radicular pain demonstrated that the area under the ROC curve was 0.667,with 73.3%sensitivity and 60%specificity.(2)According to univariate logistic regression analysis,pain during sitting position(+),pain during lying position(+),intermittent claudication(+),Kemp sign(+),and piriform muscle tension test(+)were significantly associated with LFS with radicular pain(P<0.05)in patients with different types of lumbar spinal stenosis associated with radicular pain.According to multivariate logistic regression analysis,piriformis tension test(+)was found to be an independent influencing factor for the diagnosis of LFS with radicular pain(95%CI 2.464-40.786,P=0.001).Receiver operating characteristic(ROC)curve analysis based on piriformis tension test(+)for the diagnosis of LFS with radicular pain demonstrated that the area under the ROC curve was 0.726,with a sensitivity of 56.7%and a specificity of 88.5%.(3)According to univariate logistic regression analysis,age,pain relief in anteversion(+),Kemp sign(+),and straight leg raise test(+)were significantly associated with LFS with radicular pain(P<0.05)in patients with central\paracentral lumbar disc herniation and lumbar foraminal stenosis with radicular pain.According to multivariate logistic regression analysis,pain relief in anteversion(+)(95%CI 1.202-15.195,P=0.025),Kemp sign(+)(95%CI 1.767-27.538,P=0.006),straight leg raise test(+)(95%CI 0.047-0.647,P=0.009)were all independent influencing factors in LFS patients with radicular pain.Receiver operating characteristic(ROC)curve analysis based on the risk score for the diagnosis of LFS demonstrated that the optimal diagnostic cut-off value was 6 points,with an area under the curve of 0.793,sensitivity of 63%and specificity of 88%.Conclusions:Patients with LFS have specific clinical symptoms and signs,which have differential diagnostic value in different types of radicular lumbar disease.TCM Syndromes types provide a differential diagnosis for LFS to some extent.The results of this study may improve the etiologic diagnosis and provide a rational and individualized diagnosis of symptomatic LFS.2.Conventional imaging features of lumbar foraminal stenosis and correlation with clinical featuresObjective:This study aimed to provide a theoretical basis for the diagnosis of LFS by analyzing the imaging features.Also to evaluate the degree of specific foraminal morphological changes and the relationship between the clinical features.Methods:This retrospective analysis was conducted by using the clinical data obtained from 328 low back-related leg pain patients who underwent lumbar spine endoscopic surgery at the pain department of China Japan Friendship Hospital,between January 2015 to February 2020.LFS and LCS patients were identified by preoperative diagnosis,intraoperative exploration,and postoperative outcomes.The imaging features of both cohorts and the diagnostic value of quantitative imaging features were evaluated.In addition the correlations between different imaging features,as well as between imaging features and clinical features,were also analyzed.Results:(1)LFS is more common in lumbar degenerative diseases,in which foraminal stenosis is most frequently affected at the level of L4/5(53.3%).(2)X-ray analysis of the alignment characteristics of the spine in the LFS group revealed that compared with the LCS group,the range of motion of the sagittal plane was significantly larger at the L5-S1 intervertebral foramen level(P<0.001)and the Segmental lordotic angle was significantly smaller at the L3-4/L4-5 intervertebral foramen level(P<0.05).In addition,the horizontal displacement distance and coronal Cobb angle were significantly larger in the LCS group(P<0.01).(3)Observation of the structural characteristics in the LFS group by CT revealed that compared with the LCS group,the intervertebral foramen area was significantly decreased in the LFS group.The LFS group also had significantly lower intervertebral foramen height,intervertebral space height,vertebral height,and pedicle height.The area and N-E angle of the superior articular process area were significantly larger in the LFS group than in the LCS group.The facet degeneration score and the incidence of vaccum phenomena were also significantly higher in the LFS group.(4)Through MRI examination,the LFS group was found to have higher lumbar foraminal stenosis score and lumbar disc degeneration sore at responsible intervertebral foramen segments than LCS group.The incidence of Modic change and Schmorl's nodules in the LFS group were also higher than those in the LCS group,all of which were statistically significant(P<0.05).(5)According to the correlation analysis,significant correlations were found between different imaging features in the LFS group(correlation coefficients ranging from-0.824 to+0.886).There was a significant positive correlation between foraminal height and foraminal area(r=0.554)and a low negative correlation with N-E angle(r=-0.368);There was a low positive correlation between foraminal width and foraminal area(r=0.444);There was a highly significant correlation between facet degeneration grade and the superior articular process area(r=0.886);The grade of disc degeneration was negatively correlated with the height of the mid and posterior intervertebral height(r=-0.775,r=-0.824).There was a low positive correlation between disc degeneration grade and vacuum phenomena(r=0.420).There was a low positive correlation between disc degeneration grade and wedging angle(r=0.498).(6)According to the quantitative imaging findings,the intervertebral foramen area(<36.96 mm2),intervertebral foramen height(<9.34 mm),middle intervertebral height(<6.83 mm),posterior intervertebral height(<3.95 mm),and superior articular process area(<145.63 mm2)were highly sensitive and specific for the diagnosis of LFS in patients with LFS and LCS with radicular pain.(7)According to logistic regression analysis,there were correlations between buttock pain(+),pain on sitting(+),pain when recumbent(+),intermittent claudication(+),and piriform muscle tension test(+)and imaging features of LFS(P<0.05),but no correlations between the remaining clinical features and imaging characteristics.Conclusions:Conventional imaging examination has an important diagnostic value for lumbar foraminal stenosis,which can effectively improve the diagnostic rate of symptomatic lumbar foraminal stenosis and provide a theoretical basis for formulating rational surgical treatment in the clinic.Patients with LFS have specific imaging features;There is a correlation between imaging features.This appears to constitute a more complex system of LFS that is not confined to a particular abnormal anatomy;The relationship between imaging features and clinical features provides an objective basis for the specific clinical symptoms of LFS.The evaluation of abnormal anatomical features of intervertebral foramen by combining conventional imaging examination has an important diagnostic value for LFS.3.Identification of differentially expressed genes and key pathways of LFS and Study on the law of Chinese medicineObjective:In this study,we comprehensively observed the differentially expressed genes and their functional pathways and chinese herbal medicine(CHM)for neuropathic pain induced by dorsal root ganglion injury based on bioinformatics and network pharmacology.The aim was to excavate the relevant laws of CHM on LFS and to reveal the material basis and molecular mechanism of CHM acting on neuropathic pain induced by dorsal root ganglion injury related to LFS.Methods:For microarray data from the GEO database,data processing and screening of differentially expressed genes were performed,and the differentially expressed genes were subjected to bioinformatics analysis to establish the protein-protein interaction(PPI)network for core targets,and the core targets were used as entry points to further screen candidate components and key components,relevant herbs were collected according to the obtained component lists,and the target-component-herb network was finally successfully constructed,the complex relationships between targets,components and herbs were systematically analyzed.Results:(1)After normalization and processing of the data for differentially expressed genes between the CCD group and sham group,a total of 1510 differentially expressed genes were screened,of which 892 were upregulated genes and 618 were downregulated genes,considering the spinal dorsal root ganglia and differentially expressed genes as potential targets for neuropathic pain.The two sets of gene data were comparable by principal component analysis(PCA),and the sample reproducibility was found to be good by the heat map and could be used for subsequent studies.(2)The significant pathways,biological processes,cellular components and molecular functions of up-regulated genes mainly involved cytokine-cytokine receptor interaction pathway,cell adhesion molecules,PI3K-Akt signaling pathway,chemokine signaling pathway,TNF signaling pathway,cytokines and immune response,etc.The significant pathways,biological processes,cellular components and molecular functions of down regulated genes were mainly involved,neuroactive ligand receptor interaction pathway,glutamatergic synaptic pathway,PPAR signaling pathway,cAMP signaling pathway,AMPK signaling pathway,synaptic signal transmission,synaptic membrane,gated channel activity,calcium ion binding and so on.(3)Using the cytoHubba assay,10 core targets were identified,among which CASP3,IL-6,TP53,MMP9,and IGF1 had relatively clear mechanisms of action in neuropathic pain.(4)The key components obtained through core targets in this study include quercetin,kaempferol,luteolin,ursolic acid,oleanolic acid,apigenin.(5)The core herbs accessed through the target-component-herb network included Shaji,Mahuang,Zisu,Yansui,Jinyinhua,Chaihu,and others.According to the current study,Shaji,Mahuang,Jinyinhua,Chaihu,and Huangqin have been found to have the most therapeutic potential in neuropathic pain.(6)Based on the analysis of the herbs,it was found that the herbs were mostly bitter and belongs to the liver meridian..Conclusion:Hub genes such as CASP3,IL-6,TP53,MMP9,and IGF1 and related functional pathways are important in the development of NP induced by DRG injury.At the same time,it provides a theoretical basis for the development of molecular diagnosis and therapeutic targets for LFS;The key components and Chinese herbs have potential clinical applications in NP induced by DRG injury and provide references for prescription exploration and subsequent experimental studies of LFS with radiculopathy.