Factors of Intervertebral Disc Rehydration after Percutaneous Endoscopic Lumbar Discectomy

Abstract

Percutaneous endoscopic lumbar discectomy (PELD) is an effective surgical option for lumbar disc herniation (LDH) but is associated with lumbar intervertebral disc rehydration in some patients. However, the incidence of rehydration is not clearly, and only a few studies have discussed this in detail. The study aimed at investigating the factors influencing intervertebral disc rehydration in a series of patients with LDH who underwent PELD. Ninety-six patients with single-level LDH who underwent PELD at Shenzhen Traditional Chinese Medicine Hospital from October 2013 to May 2021 were studied. The relevant data of the patients were recorded such as age, course of disease, sex, body mass index (BMI), diabetes mellitus, hypertension, smoking status, and postoperative exercise; imaging factors such as Modic changes of adjacent vertebrae at surgical level, Pfirrmann grade, degree of disc herniation (Komori classification), and spinal canal morphology; peripheral blood factors such as blood routine parameters, C-reactive protein level, erythrocyte sedimentation rate (ESR), and Th1/Th2 subgroup analysis; and operation-related factors such as surgical approach, length of operation, and amount of blood loss. Univariate analysis and binary logistic regression analysis were conducted to determine the influence of the above parameters on disc rehydration. Our results showed that Young patients with intervertebral disc herniation with a short course of disease, no smoking history, not overweight, no history of diabetes, with intervertebral disc herniation type of Komori Type C, Pfirrmann grade IV, and no adjacent vertebral Modic changes, coupled with high levels of mononuclear cells and TNF-α in peripheral blood, may be more prone to rehydration after PELD.

Introduction

Intervertebral disc rehydration (IDR) refers to the change of intervertebral disc signal from low to high in T2-weighted magnetic resonance imaging (MRI)¹. However, the mechanism underlying IDR has not been studied in detail. 

Mechanical deformation and inflammatory mediators lead to disc degeneration including structure destruction and cell-mediated composition change, characterized by early changes in biochemical signals including loss of proteoglycans, increased osmotic pressure, and reduced hydration; late changes in morphology including stenosis of the intervertebral disc; and the occurrence of neurological symptoms²，³. MRI is ideal to study the degeneration and herniation of lumbar intervertebral disc⁴; the water-fat separation technology of MRI can non-invasively determine the degree of intervertebral disc degeneration (IDD) and quantitatively measure the water signal fraction of lumbar intervertebral disc nucleus pulposus⁵.

In previous clinical studies, IDR was found to occur in some LDH patients after percutaneous endoscopic lumbar discectomy (PELD), but its incidence remains unclear. To clinically predict the incidence of IDR and help in the prognosis of postoperative PELD, we analyzed the following using univariate analysis and logistic regression analysis: clinical factors (age, course of disease, sex, body mass index (BMI), history of diabetes mellitus, hypertension, and smoking status); imaging factors (Modic changes in adjacent vertebrae during surgery, Pfirrmann grade, degree of disc herniation (Komori classification), and spinal canal morphology); peripheral blood factors (blood routine, C-reactive protein level, erythrocyte sedimentation rate (ESR), and Th1/Th2 subgroup analysis); and operation-related factors (surgical approach, length of operation, and amount of blood loss). 

Methods

Study design and patient population.

We retrospectively analyzed 96 patients with single-level LDH who underwent PELD at Shenzhen Traditional Chinese Medicine Hospital from October 2013 to May 2021. Based on whether rehydration occurred at the last follow-up, patients were divided into rehydration group (41 cases) and non-rehydration group (55 cases). Inclusion criteria were: (1) single segment LDH as confirmed by preoperative imaging examination; (2) no improvement in symptoms even after more than half a year of non-surgical treatment; (3) underwent PELD; and (4) a follow-up period of at least 1 year. Exclusion criteria were: (1) significant instability of the responsible segment as revealed by preoperative imaging; (2) spondylolysis of the responsible segment; (3) history of other lumbar surgery; and (4) infection, trauma, or spondylolisthesis. The study involving human participants was reviewed and approved by the Ethics Committee of Shenzhen Traditional Chinese Medicine Hospital. This study also complied with the Declaration of Helsinki for investigation in humans. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Surgical Procedure

Epidural anesthesia was used in all patients. After successful anesthesia, the patients were made to lie in the prone position on the operating table, and their hips and knees were disinfected and covered with towels.

Translaminar approach: Percutaneous puncture was performed with a 10-ml syringe needle 2 cm from the posterior median of the body surface of the responsible intervertebral space, and C-arm fluoroscopy was used to confirm the responsible intervertebral disc. Then, the skin was incised using an intervertebral disc puncture needle and using a 0.7-cm pencil, the incision was expanded such that the intervertebral foramen is seen and the degenerated intervertebral disc nucleus pulposus tissue was removed. Ultrasound-guided vertebral canal decompression was used when necessary. Radiofrequency ablation followed by percutaneous adhesiolysis was performed after thorough decompression. The floating disc was checked. Methylprednisolone sodium succinate 40 mg was injected through the foraminal endoscopic channel to prevent postoperative nerve root edema.

Transforaminal approach: An 18-gauge puncture needle was used to enter the posterior third of the intervertebral space through the foraminal area 8–10 cm adjacent to the intervertebral space under the guidance of the C-arm machine, and ioparol contrast agent was injected. The C-arm machine showed the rupture of the annulus fibrosus and herniation of the intervertebral disc. The rest of the procedure is the same as that used in the translaminar approach, except that betamethasone injection (0.5 ml) was used to prevent postoperative edema of the nerve root before suturing off the skin incision.

Postoperative treatment: Bed rest for 1 month after the operation, a waist belt to get out of bed, and oral neurotrophic drugs.

Data Collection

Differences in sex, job type, age, BMI, surgical approach, hypertension, diabetes, duration of disease, smoking status, and other baseline conditions were compared between the two groups. In addition, preoperative peripheral blood-related indicators including count of leukocytes, neutrophils, lymphocytes, monocytes, and platelets, hemoglobin level, ESR, C-reactive protein level, and Th1/Th2 subgroup analysis, including levels of IL-2, IL-4, IL-6, IL-10, TNF-α, interferon (INF)-γ, were compared between the two groups.

Lumbar MRI was performed with a superconducting 1.5T magnetic resonance imager (Siemens, Germany) to detect the signals of lumbar intervertebral discs before and after surgery. Detection conditions: Magnetic acoustic intensity was 0.35 Tes/a, and 11 layers were scanned in sagittal position (interlayer distance was 1.25 mm; layer thickness was 5 mm).

Evaluation of intervertebral disc rehydration: Intervertebral disc water content can be reflected by the intensity of intervertebral disc signal on MRI T2-weighted images (T2WI). Ideally, MRI should be performed using the same MRI device before and at the last follow-up, but not every patient can meet this requirement. To solve this problem, average calibrated disc signal (CDS) proposed by Fay⁶ was used. On the cross-sectional T2WI of the center of the intervertebral disc, the gray value of the central area of the L2/3 intervertebral disc (the circular area with a radius of 1 cm) was selected as a reference and compared with the gray value of the central area of the surgical segment. This ratio eliminates the influence of other MRI device parameters and reflects the intervertebral disc signal intensity; therefore, it can be used to compare patient data between two MRI examinations.

In addition, IDD grades were assigned at the implanted segment according to the Pfirrmann classification of lumbar IDD. Grade I: the structure of the vertebral disc shows uniform white hyperintensity, and the height of the disc is normal; Grade II: the structure of the bay disk is characterized by uneven white high signal. The annulus fibrosus and nucleus pulposus were distinct, with or without horizontal gray bands; Grade III: intervertebral disc structure with uneven signal intensity and gray signal intensity; the difference between annulus fibrosus and nucleus pulposus is unknown. The disc height is normal or slightly decreased; Grade IV: the signal of intervertebral disc structure is not uniform, showing a black low signal. The difference between the nucleus pulposus and annulus fibrosus disappeared, and the disc height was normal or moderately decreased; Grade V: the signal of intervertebral disc structure is not uniform, showing a black low signal. The difference between the nucleus pulposus and annulus fibrosus disappeared, and the intervertebral space collapsed.

Based on the degree of displacement of the protrusion, LDH was divided into three types by the Komori typing method. Type A: the displacement of the protrusion did not exceed 1/3 of the adjacent vertebral body; Type B: the protrusion displacement does not exceed 2/3 of the adjacent vertebral body; Type C: the protrusion is displaced by more than 2/3 of the adjacent vertebral body or accompanied by distance.

Modic changes in the adjacent vertebrae of the operative segment: whether there are Modic changes in the vertebrae can be determined based on preoperative MRI results. Type 1: T1 low signal, T2 high signal; Type 2: T1 high signal, T2 medium signal; Type 3: T1 low signal, T2 low signal.

Spinal canal morphology: Based on transverse MRI images, spinal canal morphology was divided into three types: elliptic, triangular, and trilobated.

Statistical Analyses

SPSS 24.0 software was used for statistical analysis. The measurement data conformed to normal distribution. All variables were analyzed to screen for factors that may affect reabsorption. The measurement data were analyzed by independent t-test and further analyzed by Chi-square test. Variables with statistical significance were further analyzed using binary logistic regression to identify the factors affecting LDH rehydration. P < 0.05 was considered statistically significant.

Results

Results Of Multivariate Analysis

Binary logistic regression analysis showed that patients with disease duration ≤ 2 years, normal BMI, non-smoking status, no history of diabetes, Komori type C, Pfirrmann grade IV, no adjacent vertebral Modic changes, mononuclear cells > 0.60 (10⁹/L), TNF-α level > 2.5 pg/ml (P < 0.05) influenced rehydration (Tables 4 and 5). The imaging findings of typical cases are presented in Figs. 1 and 2.

Discussion

There are many causes of lower back pain, among which IDD is the most important⁷. The onset of lumbar IDD is characterized by changes in lumbar structure, which may be secondary to facet joint degeneration and release of inflammatory factors and other factors causing back pain. In young individuals, the nucleus pulposus and annulus fibrosus are distinctly separated ². However, degeneration of the intervertebral disc causes type Ⅱ collagen in nucleus pulposus tissue to be gradually replaced with type Ⅰ collagen; the synthesis ability of proteoglycans gradually decreases, which results in the gradual loss of the boundary between nucleus pulposus and annulus fibrosus, and the water retention ability of nucleus pulposus tissue gradually decreases as well⁸. During IDD, the expression of extracellular matrix catabolism-related proteases increased significantly, including matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase with thrombospondin motifs family (ADAMTS), thus promoting the degradation of polysaccharides and type Ⅱ collagen in nucleus pulposus tissues⁹. The imbalance of proteoglycans and type II collagen is the main sign of impaired nucleus pulposus cell function. The calcification and permeability of endplate cartilage also decreased gradually, which affected the damage and repair of nucleus pulposus tissue and further aggravated nucleus pulposus tissue damage. Changes in the structure of the nucleus pulposus decrease the height of the intervertebral disc and lead to a series of spinal degenerative diseases due to the disturbance of spinal biomechanics¹⁰, ¹¹. However, we found that some patients with LDH showed significant improvement in disc signal after PELD. This phenomenon may be a manifestation of improved intervertebral disc microenvironment after surgery.

Analysis of clinical factors such as age, course of disease, and sex showed that patients with course of disease ≤ 2 years were prone to rehydration. The period of rehydration was 6 months to 2 years after PELD, and the active stage of rehydration occurred within 1 year after PELD. The age of patients with rehydration ranged from 22 to 54 years. Although there is no clear evidence that age is related to the occurrence of rehydration, our results show that middle-aged and young patients have a higher probability of rehydration, while elderly patients are not prone to rehydration due to high IDD.

Our results suggest that patients with normal BMI have a higher probability of rehydration than obese patients. Previous studies have shown obesity to be a risk factor for IDD, and the increase in adipose tissue¹², especially white adipose tissue, is related to the overexpression of TNF-α, IL-1β, and IL-6 and the phenotype transformation of macrophages, which are all factors promoting IDD¹³. In addition, serum leptin content in obese patients significantly increased and the intervertebral disc cells expressed leptin receptors¹⁴. The combination of the two increased the synthesis of proteolytic enzymes in the intervertebral disc, which accelerated IDD⁸.

Diabetes is one of the most common diseases of the endocrine system. Agius¹⁵ found that compared with non-diabetes patients, diabetes patients showed more intervertebral height loss, and hyperglycemia might cause metabolic and nutritional dysfunction of the intervertebral disc by promoting the glycosylation and modification of proteins in intervertebral disc tissue, thus causing degeneration. The results of this study suggest that patients with diabetes mellitus are less likely to have intervertebral disc rehydration after surgery than patients without diabetes. The main mechanisms of diabetes promoting IDD are as follows: when cells are exposed to high glucose, their internal glucose homeostasis is disturbed, which impedes glucose metabolism and affects energy metabolism¹⁶. High glucose leads to hardening of intervertebral disc endplate cartilage and narrowing of internal microvessels, which reduces the nutrient supply of nucleus pulposus cells and the efficiency of substance exchange with the external environment of cells¹⁷. A high glucose environment can mediate and accelerate cell aging, impair mitochondrial function, lead to the accumulation of oxidative stress products, and eventually cause apoptosis of intervertebral disc cells. Other mechanisms such as increased autophagy in the nucleus pulposus, promotion of inflammation, aggregation of glycosylated end products and resulting osmotic stress, hypoxia, and acidic environment may promote disc degeneration¹⁸, ¹⁹.

Analysis of the herniation degree of intervertebral disc showed that Komori classification was the influencing factor of LDH rehydration, with Komori C type being the primary factor associated with dissociation. Komori type A was the least prominent. The results of this study showed that protruding hernias were more prone to rehydration after operation. Due to the high degree of protrusion, the free and prolapsed hernia is often accompanied by rupture of the posterior longitudinal ligament; the protruding tissue is exposed to the epidural vascular environment, thus triggering phagocytosis of macrophages and induction of immune responses, mediating rehydration. This may be one of the important mechanisms of rehydration. Our results show that abnormal expression of TNF-α and increased monocyte count in Th cell subsets are an important factor affecting the rehydration of LDH. Immune cells are widely involved in the occurrence and development of skeletal degenerative diseases²⁰. Studies have shown that degraded nucleus pulposus and annulus fibrosus produce a large number of pro-inflammatory factors, including IL-1α, IL-β, TNF-α, and C-C motif chemokine ligand (CCL)²¹. These inflammatory chemokines further recruit immune cells to infiltrate the intervertebral disc, exacerbating the inflammatory response. T-helper cells (Th), a subtype of T cells, mainly consist of Th1 and Th2. The balance between the two is very important for maintaining local homeostasis. Once the balance gets disturbed, the secretion of inflammatory factors will be disrupted, thus causing diseases. Yao²² reported that the amount of Th1 in the nucleus pulposus tissue of rats with IDD increased significantly, reaching a peak on the 14th day after model development and decreasing on the 28th day. Other studies have shown that IL-4 secreted by Th2 can alleviate intervertebral disc inflammation by binding IL-4 receptor α of intervertebral disc cells; particularly, the expression level of this receptor is higher in the herniated intervertebral disc, suggesting the protective effect of Th2 on IDD²³, ²⁴.

Conclusion

In conclusion, analysis of the influencing factors of LDH postoperative rehydration showed that age, disease course, BMI, smoking, history of diabetes mellitus, Komori classification, Pfirrmann grade, Modic changes, and Th1/Th2 subgroup in peripheral blood were independent factors (P < 0.05). In particular, young patients with disease duration ≤ 2 years, normal BMI, non-smoking status, Komori classification type C, Pfirrmann grade IV, no adjacent vertebral Modic changes, mononuclear cells > 0.60 (10⁹/L), and TNF-α level > 2.5 (pg/ml) influenced rehydration. Young patients with intervertebral disc herniation with a short course of disease, no smoking history, not overweight, no history of diabetes, with intervertebral disc herniation type of Komori Type C, Pfirrmann grade IV, and no adjacent vertebral Modic changes, coupled with high levels of mononuclear cells and TNF-α in peripheral blood, may be more prone to rehydration after PELD. However, the sample size of this study is small and no prospective randomized controlled study has been conducted; therefore, the results are limited and need to be further investigated in large-scale prospective clinical studies.

Abbreviations

LDH, Lumbar disc herniation; 

PELD, Percutaneous endoscopic lumbar discectomy; 

IDR, Intervertebral disc rehydration

IDD, Intervertebral disc degeneration

BMI, Body mass index

CT, Computed tomography; 

MRI, Magnetic resonance imaging

ESR, Erythrocyte sedimentation rate

TNF, Tumor necrosis factor

IL, Interleukin

INF, Interferon

CDS, Calibrated disc signal 

MMP, Matrix metalloproteinase 

ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs

Declarations

Data availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

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