Characteristics in patients with very early therapeutic response of condoliase chemonucleolysis for lumbar disc herniation.

INTRODUCTION: Treatment of lumbar disc herniation (LDH) using condoliase chemonucleolysis (CC) requires more time than surgery to demonstrate therapeutic effects. This study aimed to identify patients who show significant improvement in leg pain very early after CC and to determine pretreatment factors that can predict a very early therapeutic response. METHODS: The study included 52 patients who underwent CC for treatment-resistant LDH. Scores for low back and leg pain measured by a numerical rating scale were assessed at four time points (1 day, 1 week, 1 month, and 3 months after CC). Patients who reported subjective pain relief the day after treatment and further exhibited an improved straight leg raising (SLR) angle compared to pretreatment were classified as "very early responders (VER)". RESULTS: Of the 52 patients, 39 (75%) were VER, and 13 (25%) were non-VER. The VER showed earlier improvement in leg pain. The VER had a significantly higher proportion of positive SLR test patients (p = 0.01) and a significantly smaller pretreatment SLR angle compared to the non-VER (VER vs. non-VER: 40.6 ± 19.0 vs. 63.1 ± 16.9, p < 0.001). There were no significant differences in the level, type, and size of LDH and the disc regression rate between the two groups. CONCLUSIONS: Patients with a smaller pretreatment SLR angle are more likely to experience very early or early symptomatic relief, with a significant and sustained reduction in leg pain up to 3 months after CC treatment.

"Advancements in minimally invasive treatment for lumbar disc herniation: insights into condoliase and chondroitin sulfate ABC endolyase".

This study examines the efficacy and safety of condoliase chemonucleolysis (CC) in treating lumbar disc herniation (LDH) and highlights emerging alternatives like chondroitin sulfate ABC endolyase. Research indicates that condoliase, an enzyme used to degrade glycosaminoglycans in the nucleus pulposus, provides effective and prompt relief of leg pain, with significant reductions observed within a day of treatment. Studies reveal that a lower pretreatment straight leg raising (SLR) angle may predict early symptom relief, and condoliase is generally effective at doses up to 1.25 U, balancing efficacy and safety. Despite promising results, concerns about long-term safety, including disc height reduction and imaging changes, persist. Additionally, chondroitin sulfate ABC endolyase shows potential as a safer and more effective alternative, though further research is needed to optimize treatment protocols and assess long-term outcomes. Future investigations should address current limitations, such as small sample sizes and short follow-up periods, to better understand the long-term benefits and risks of these treatments.

Effect of DiscoGel treatment of the intervertebral disc at MRI.

AIM: To determine the impact of ethanol gel chemonucleolysis (EGCh) on the radiological picture of the treated intervertebral disc, the relationship between the initial radiological status and the clinical status of the patient after EGCh treatment, and the optimal radiographic criteria for qualifying a patient for EGCh treatment. MATERIALS AND METHODS: The study involved a group of 45 patients (25 men and 20 women) aged 23-68 years (46 ± 11) who underwent an EGCh procedure after qualification, radiography, and clinical questionnaire evaluation. RESULTS: The results showed a decrease in the size of the protrusion and Gadolinium-Enhanced (GI) zone in the treated intervertebral disc. The presence of a high-intensity zone (HIZ) on baseline magnetic resonance imaging was found to be a good predictor of the timing and outcome of treatment, and an increase in disc height was observed in adjacent segments. CONCLUSION: These findings suggest that EGCh is a promising treatment for spine diseases, and the HIZ on baseline magnetic resonance imaging can be used as a qualification criterion for this procedure.

Condoliase chemonucleolysis for lumbar disc herniation: A post-hoc follow-up study of patients in previous clinical trials.

BACKGROUND: Chemonucleolysis with condoliase significantly improved clinical symptoms in patients with lumbar disc herniation. We evaluated the surgical intervention rate and outcomes for >1 year after condoliase treatment. METHODS: This was a follow-up study of patients who received condoliase or placebo in two previous randomized, placebo-controlled clinical trials with 1-year follow-ups. A post-treatment surgery survey and on-site examination were administered and patients' data from the clinical trial records and additional interview data were analyzed to evaluate the surgical intervention rate. Patients' lumbar disease symptoms, Oswestry Disability Index, and imaging features were evaluated. RESULTS: Among the patients (condoliase, n = 228; placebo, n = 128) enrolled in the clinical trials, additional post-treatment surgery data were available for 231 patients after the clinical trials ended, and 179 patients underwent post-trial examinations, at least 5 years and 17 months after the end of the clinical trials. The surgical intervention rate in the placebo and condoliase groups was 20.7% (95% confidence interval: 14.2-29.7) and 13.4% (95% confidence interval: 8.8-20.2), respectively. The mean change in Oswestry Disability Index score from pre-injection in placebo and condoliase groups was -24.7 ± 15.0 and -32.7 ± 18.6 (between-group difference: -8.0 ± 17.3; 95% confidence interval: -13.2 to -2.7). Modic Type 2 changes were observed, particularly in the condoliase group. No relationship between lumbar disease symptoms and change in imaging features was found. CONCLUSIONS: This follow-up study more than 1 year revealed no new safety concerns of condoliase. However, because the study had several limitations, such as large loss of follow-up, further research is needed.

Disc degeneration could be recovered after chemonucleolysis with condoliase.-1 year clinical outcome of condoliase therapy.

BACKGROUND: Condoliase-induced chemonucleolysis is a less-invasive alternative treatment for lumbar disc herniation (LDH); however, its long-term clinical outcome is still unclear. This study aimed to investigate 1-year clinical outcomes and assess radiographs after chemonucleolysis with condoliase. METHODS: We enrolled patients with LDH who received condoliase injection with a follow-up period of >1 year. Sixty patients (37 men, 23 women; mean age, 44.5 ± 18.9 years; mean follow-up period, 22.0 ± 6.0 months) were analyzed. Changes in disc height and degeneration were evaluated using magnetic resonance imaging. Visual analog scale (VAS) scores for leg and back pain and the Oswestry disability index (ODI) were obtained. All data were assessed at baseline, 1-month, 3-month, and 1-year follow-up. RESULTS: Surgical treatment was subsequently required in 8 patients (12.5%) after condoliase therapy. Their ODI and VAS scores for leg pain and back pain significantly improved at 1 year, as in those who received condoliase therapy only. On MRI, progression of Pfirrmann grade was observed in 23 patients (44.2%) at 3 months; however, 8 patients recovered to baseline at 1 year. The mean disc height decreased at 3 months; however, it recovered at 1 year. Disc height recovery (disc recovery rate >50%) was observed in 30.8% of the patients. Patients with disc height recovery were significantly younger than those without. Patients with longer symptom duration (≥1 year) showed significantly lower rates of effectiveness compared with those with shorter symptom durations (<1 year). CONCLUSIONS: Chemonucleolysis with condoliase is a safe and minimally invasive treatment. Disc degeneration induced by chemonucleolysis could be recovered, particularly in younger patients. Prolonged symptom duration had adverse effects on outcome; thus, therapeutic intervention at the optimal time is needed.

Predictive Factors for Poor Outcome following Chemonucleolysis with Condoliase in Lumbar Disc Herniation.

Background and Objectives: Condoliase, a chondroitin sulfate ABC endolyase, is a novel and minimally invasive chemonucleolytic drug for lumbar disc herniation. Despite the growing number of treatments for lumbar disc herniation, the predicting factors for poor outcomes following treatment remain unclear. The aim of this study was to determine the predictive factors for unsuccessful clinical outcome following condoliase therapy. Material and Methods: We performed a retrospective single-center analysis of 101 patients who underwent chemonucleolysis with condoliase from January 2019 to December 2021. Patients were divided into good outcome (i.e., favorable outcome) and poor outcome (i.e., requiring additional surgical treatment) groups. Patient demographics and imaging findings were collected. Clinical outcomes were evaluated using the numerical rating scale and Japanese Orthopaedic Association scores at baseline and at 1- and 3-month follow-up. Pretreatment indicators for additional surgery were compared between the 2 groups. Results: There was a significant difference in baseline leg numbness between the good outcome and poor outcome groups (6.27 ± 1.90 vs. 4.42 ± 2.90, respectively; p = 0.033). Of the 101 included patients, 32 received a preoperative computed tomography scan. In those patients, the presence of calcification or ossification in disc hernia occurred more often in the poor outcome group (61.5% vs. 5.3%, respectively; p < 0.001; odds ratio = 22.242; p = 0.014). Receiver-operating characteristics curve analysis for accompanying calcification or ossification showed an area under the curve of 0.858 (95% confidence interval, 0.715−1.000; p = 0.001). Conclusions: Calcified or ossified disc herniation may be useful predictors of unsuccessful treatment in patients with condoliase administration.

Percutaneous ozone nucleolysis for lumbar disc herniation.

PURPOSE: All percutaneous minimally invasive disc treatments are typically indicated to contained disc herniations. Our study's aim is to evaluate prospectively the efficacy of ozone nucleolysis in the treatment of either contained or uncontained lumbar disc herniations. METHODS: Fifty-two patients, aged 27-87 years, with symptomatic herniated lumbar discs, without migration, sequestration, or severe degenerative disc changes, who failed conservative treatment, were included in our study. The patients underwent fluoroscopic-guided intradiscal oxygen-ozone mixture injection (5 ml) at a concentration of 27-30 µg/ml and periradicular injection of the same O2-O3 mixture (10 ml), steroid (1 ml), and local anesthetic (1 ml). Clinical outcomes were evaluated, based on the Oswestry Disability Index (ODI) and pain intensity (0-5) scale results, obtained initially and at 2- and 6-month controls. Our results were analyzed by ANOVA and chi-squared (χ2) tests. RESULTS: Our initial results obtained at 2-month control were promising, indicating a significant decrease in pain disability and intensity in 74% (37) and 76% (38) of the patients respectively, and minimally increased to 76% (38) and 78% (39) at 6-month control (P < 0.001 and CI 99.9%). The mean preprocedure ODI and pain intensity scores were 35 ± 14.36 and 2.38 ± 0.90, respectively, which were reduced to 19.36 ± 13.12 and 1.04 ± 0.92 at 6-month control. Our failure had been mostly related to long symptoms duration of more than 1 year. No complications were recorded. CONCLUSION: Ozone nucleolysis is a safe cost-effective minimally invasive technique for treatment of contained and uncontained lumbar disc herniations.

Radiopaque Gelified Ethanol Application in Lumbar Intervertebral Soft Disc Herniations: Croatian Multicentric Study.

Objective: Minimally invasive percutaneous spinal procedures are popular in trying to reduce spinal pain. The aim of this paper is to evaluate the safety of intervertebral disc chemonucleolysis and to report the effectiveness of a percutaneous, minimally invasive treatment for contained herniated intervertebral discs in the lumbar spine using the recently marketed radiopaque gelified ethanol. Methods: Pain relief before and after the procedure was self-evaluated by each patient using a verbal numeric scale (VNS) ranging from 0 to 10. Patients were also scored prior to procedure and after chemonucleolysis during several follow-up periods using the Roland-Morris low back pain and disability questionnaire (RMQ). Follow-up periods were defined as 0-6, 6-12, 12-18, 18-24, and 24-30 months. Clinically significant functional improvement (CSFI) was defined as a decrease of five or more points on the RMQ scale and a decrease of at least 50% of pain intensity using VNS. Results: Using the RMQ scale, CSFI was achieved in 20/29 patients in the first follow-up period, 20/27 patients in the second follow-up period, 9/12 patients in the third follow-up period, 8/9 patients in the fourth follow-up period, and 4/4 patients in the last follow-up period. Using the VNS rating, CSFI was accomplished in 19/29 patients in the first follow-up period, 19/27 patients in the second follow-up period, 9/12 patients in the third follow-up period, 8/9 patients in the fourth follow-up period, and 4/4 in the last follow-up period. Conclusions: Intradiscal application of gelified ethanol may be effective in pain reduction using the VNS and Roland-Morris low back pain and disability questionnaire. The treatment is safe and easy to handle.

Indications and efficacy of O2-O3 intradiscal versus steroid intraforaminal injection in different types of disco vertebral pathologies: a prospective randomized double-blind trial with 517 patients.

OBJECTIVE: The aim of this study was to prospectively evaluate the clinical efficacy of perigangliar steroid and local anesthetic with intradiscal O2-O3 injection versus steroid and local anesthetic intraforaminal injection in different types of herniation and grade of disc degeneration. MATERIALS AND METHODS: A total of 517 patients were randomly assigned to two groups. Control Group (159 men, 101 women; age range 25-89 years) underwent steroid and local anesthetic intraforaminal injection. Study Group (163 men, 94 women; age range 22-92 years) underwent the same treatment with addiction of O2-O3 intradiscal injection. Procedures were performed under computed tomographic guidance. Visual Analog Scale Questionnaire was administered before treatment and at intervals, the last at 6-month follow-up. Results were compared with Kruskal-Wallis and t test. RESULTS: After 6 months, O2-O3 discolysis was successful in 106 (41.24 %) Study Group patients with extrusions compared with 9 Control Group patients (3.5 %) (P < 0.001). In 89 (34.6 %) Study Group patients with protrusions, success rate was statistically significant compared with 5 Control Group patients (1.9 %). Significant difference was detected in the presence of Grade I, II, III of Degenerated Disc in 185 of Study Group patients (68.4 %) compared with 4 Control Group patients (1.5 %). CONCLUSIONS: The addition of O2-O3 discolysis is more effective at 6 months than perigangliar steroid and local anesthetic injection, especially in cases of herniated or protruded discs and with a Grade of Disc Degeneration from mild to moderate range.

Cohort study of lumbar percutaneous chemonucleolysis using ethanol gel in sciatica refractory to conservative treatment.

PURPOSE: To investigate the efficacy of percutaneous chemonucleolysis using ethanol gel (PCEG) in alleviating radicular pain due to disc herniation after failure of conservative treatment. MATERIALS AND METHODS: After failure of conservative treatment, PCEG was performed under fluoroscopic guidance in 42 patients with sciatica >4/10 on a Visual Analog Scale (VAS) for at least 6 weeks and consistent disc herniation on MRI or CT <3 months. The VAS pain score was determined at baseline, then after 1 and 3 months. We assessed the influence of patient-related factors (age, gender, pain duration) and disc herniation-related factors (level, migration pattern, disc herniation-related spinal stenosis) on outcome of PCEG. RESULTS: Mean pain duration was 6.7 months. Pain intensity decreased by 44% and 62.6% after 1 and 3 months, respectively, versus baseline (P = 0.007). A mild improvement was noted by the rheumatologist in 30/42 (71.4%) and 36/42 (85.7%) patients after 1 and 3 months, respectively, and in 31/42 (73.8%) and 33/42 (78.6%) patients by self-evaluation. Patients who failed PCEG were significantly older (49.8 vs. 37.3 years, P = 0.03). None of the other variables studied were significantly associated with pain relief. CONCLUSION: PCEG may significantly improve disc-related radicular pain refractory to conservative treatment. KEY POINTS: • Percutaneous chemonucleolysis using ethanol gel (PCEG) is feasible on an outpatient basis. • PCEG improves disc-related radicular pain refractory to conservative treatment. • PCEG is feasible on an outpatient basis. • Failure of PCEG does not interfere with subsequent spinal surgery.

CT-guided chemonucleolysis combined with psoas compartment block in lumbar disc herniation: a randomized controlled study.

OBJECTIVES: The study was designed to evaluate the effectiveness of the combination of chemonucleolysis and psoas compartment block (PCB) for the treatment of lumbar disc herniations (LDHs) and to explore the role of PCB in managing postoperative pain of collagenase injection. METHODS: Two groups of patients (N = 192) were treated in different ways, respectively. Group A (N = 95) was treated with chemonucleolysis only (the injection of oxygen-ozone combined with collagenase into the lumbar disc and the epidural space); group B (N = 97) was treated with chemonucleolysis and PCB. After the treatment, the patients were followed-up, and the therapeutic effect was assessed at 1 week, 1 month, 3 months, and 6 months by the relative pain reduction, visual analog scale (VAS) pain scores, and the Oswestry Disability Index (ODI) scores. RESULTS: In group A, treatment success rate was 64.2% (61 of 95), 82.1% (78 of 95), 84.2% (80 of 95), and 86.3% (82 of 95) at 1 week, 1 month, 3 months, and 6 months, respectively. In group B, treatment success rate was 86.5% (84 of 97), 89.6% (87 of 97), 93.8% (91 of 97), and 91.7% (89 of 97) at 1 week, 1 month, 3 months, and 6 months, respectively. There was statistically significant difference in outcome between two groups at 1 week, but there were no statistically significant difference in outcome between two groups at 1 month, 3 months, and 6 months. VAS scores and ODI were significantly decreased in both group A and group B, when compared with the baseline values in the same group at all points of follow-up. Group B produced a significant reduction in the VAS scores and ODI when compared with group A at: 1-week, 1-month, 3-month, 6-month follow-up. CONCLUSIONS: Computer tomography (CT)-guided chemonucleolysis combined with PCB leads to rapid pain relief, fewer postoperative pain of collagenase injection happen, and should be regarded as a useful treatment for the management of LDH.

Enzymatic chemonucleolysis for lumbar disc herniation-an assessment of historical and contemporary efficacy and safety: a systematic review and meta-analysis.

Lumbar disc herniation (LDH) is often managed surgically. Enzymatic chemonucleolysis emerged as a non-surgical alternative. This systematic review and meta-analysis aims to assess the efficacy and safety of chemonucleolytic enzymes for LDH. The primary objective is to evaluate efficacy through "treatment success" (i.e., pain reduction) and severe adverse events (SAEs) rates. Additionally, differences in efficacy and safety trends among chemonucleolytic enzymes are explored. Following our PROSPERO registered protocol (CRD42023451546) and PRISMA guidelines, a systematic search of PubMed and Web of Science databases was conducted up to July 18, 2023. Inclusion criteria involved human LDH treatment with enzymatic chemonucleolysis reagents, assessing pain alleviation, imaging changes, and reporting on SAEs, with focus on allergic reactions. Quality assessment employed the Cochrane Source of Bias and MINORS tools. Meta-analysis utilized odds ratios (OR) with 95% confidence intervals (CI). Among 62 included studies (12,368 patients), chemonucleolysis demonstrated an 79% treatment success rate and significantly outperformed placebo controls (OR 3.35, 95% CI 2.41-4.65) and scored similar to surgical interventions (OR 0.65, 95% CI 0.20-2.10). SAEs occurred in 1.4% of cases, with slightly higher rates in chymopapain cohorts. No significant differences in "proceeding to surgery" rates were observed between chemonucleolysis and control cohorts. Limitations include dated and heterogeneous studies, emphasizing the need for higher-quality trials. Further optimization through careful patient selection and advances in therapy implementation may further enhance outcomes. The observed benefits call for wider clinical exploration and adoption. No funding was received for this review.

Comparison of Percutaneous Endoscopic Transforaminal Discectomy, Chemonucleolysis, Microdiscectomy, and Microendoscopic Discectomy for Symptomatic Lumbar Disc Herniation: One-year Follow-up Clinical Results and Disc Degeneration.

This study compared the 1-year clinical outcomes and disc degeneration rates after transforaminal full-endoscopic lumbar discectomy (TF-FED), condoliase injection, open discectomy (OD), and microendoscopic discectomy (MED) for lumbar disc herniation (LDH). In total, 279 patients with LDH were divided into four treatment groups: TF-FED, OD, MED, and condoliase injection. Outcomes were evaluated on the basis of the complication rate, Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), visual analog scale (VAS) scores, and the modified MacNab criteria. Surgical and hospital costs were assessed. Disc degeneration and endplate bone marrow edema were evaluated using magnetic resonance images. The mean postoperative JOABPEQ, VAS, or modified MacNab scores among the four groups had no significant differences. Additionally, the nerve injury or reoperation rate among the TF-FED, OD, and MED groups had no significant difference. However, the reoperation rate with condoliase injection was high because of residual disc herniation. Surgical and hospital costs were lower with condoliase injection and higher with OD and MED than those with TF-FED. With TF-FED and condoliase injection, the Pfirrmann grade progressed, and the disc height was significantly smaller than that with OD and MED. Endplate bone marrow edema was more common with condoliase injection and TF-FED. All groups had good outcomes. TF-FED and condoliase injection may reduce the burden of surgery because they can be performed under local anesthesia with little blood loss and low medical costs but tend to be associated with disc degeneration and endplate bone marrow edema. A randomized controlled study with a larger sample is needed.

Analysis of disk volume before and after CT-guided intradiscal and periganglionic ozone-oxygen injection for the treatment of lumbar disk herniation.

PURPOSE: To quantify the change in volume in herniated lumbar disk after computed tomography (CT)-guided intradiscal and periganglionic ozone-oxygen injection and to assess the effects of patient age, sex, and initial disk volume on disk volume changes. MATERIALS AND METHODS: A total of 283 patients with lumbar radiculopathy received a single intradiscal (3 mL) and periganglionic (7 mL) injection of an ozone-oxygen mixture (ratio, 3:97; ozone concentration, 30 µg/mL). Under CT guidance, intradiscal and periganglionic injection was performed through an extraspinal lateral approach with a 22-gauge spinal needle. All disk volume changes were evaluated on CT 6 months after the procedure in all patients. RESULTS: Initial mean disk volume was 17.37 cm(3) ± 4.70 (standard deviation; range, 8.12-29.15 cm(3)). Disk volume reduction (mean, 7.70% ± 5.45; range, 0.29%-22.31%) was seen in 96.1% of treated disks (n = 272) at 6 months after treatment and was found to be statistically significant (P < .0001). In 3.9% of patients (n = 11), disk volume increased (mean, 0.59% ± 0.24; range, 0.11%-0.81%). Patient age correlated negatively with disk volume reduction (r = -0.505; P < .0001) at 6 months after treatment, whereas initial disk volume correlated positively with volume reduction (r = 0.225; P = .00014) after therapy. No correlation was noted between patient sex and disk volume reduction after treatment (P = .09). CONCLUSIONS: Intradiscal administration of medical ozone is associated with a statistically significant volume reduction of the herniated lumbar disk. The volume-reduction effect of ozone correlates negatively with the patient's age and positively with initial disk volume.

O2-O3 chemodiscolysis: How much, how long? Retrospective outcome evaluation of different treatment sessions in partially-responder patients.

PURPOSE: To retrospectively evaluate the clinical and instrumental outcome of different treatment sessions of oxygen-ozone (O2-O3) chemodiscolysis in patients with lumbar disc herniation. METHODS: We evaluated 73 patients partially responders to a single session of oxygen-ozone (O2-O3) chemodiscolysis and submitted to multiple injections sessions. All patients completed a pre- and post-treatment clinical (VAS and modified McNab score) and instrumental MRI follow-up. Imaging evaluation included assessment of intervertebral disc area (IDA). Pre- and post-treatment differences were compared to evaluate differences in variation between groups. Correlation analysis was used to evaluate the relationship between morphological and clinical parameters. RESULTS: Based on the type and number of treatments performed, patients were divided into three groups: Group A) patients submitted to an additional periradicular anaesthetic/steroid injection; Group B) patients submitted to an additional session of intradiscal O2-O3 injection; Group C) patients submitted to two further sessions of intradiscal O2-O3 injection.The results showed an improvement of pain scores in all groups, and a smaller disc area change in group B. Comparing the differences between pre- and post-treatment features among the three different groups of patients, we did not find any statistically significant difference. Correlation analysis did not show any statistically significant correlation between the morphological changes of the intervertebral disc and the clinical output scores. CONCLUSIONS: In our retrospective observation of partially responder patients, multiple intradiscal ozone injections were not associated with a higher disc shrinkage nor superior clinical outcome compared to a single intradiscal O2-O3 application with an additional periradicular injection session.

Intradiscal oxygen-ozone chemonucleolysis versus microdiscectomy for lumbar disc herniation radiculopathy: a non-inferiority randomized control trial.

BACKGROUND CONTEXT: Low back pain with or without radicular leg pain is an extremely common health condition significantly impacting patient's activities and quality of life. When conservative management fails, epidural injections providing only temporary relief, are frequently utilized. Intradiscal oxygen-ozone may offer an alternative to epidural injections and further reduce the need for microdiscectomy. PURPOSE: To compare the non-inferiority treatment status and clinical outcomes of intradiscal oxygen-ozone with microdiscectomy in patients with refractory radicular leg pain due to single-level contained lumbar disc herniations. STUDY DESIGN / SETTING: Multicenter pilot prospective non-inferiority blocked randomized control trial conducted in three European hospital spine centers. PATIENT SAMPLE: Forty-nine patients (mean 40 years of age, 17 females/32 males) with a single-level contained lumbar disc herniation, radicular leg pain for more than six weeks, and resistant to medical management were randomized, 25 to intradiscal oxygen-ozone and 24 to microdiscectomy. 88% (43 of 49) received their assigned treatment and constituted the AS-Treated (AT) population. OUTCOME MEASURES: Primary outcome was overall 6-month improvement over baseline in leg pain. Other validated clinical outcomes, including back numerical rating pain scores (NRS), Roland Morris Disability Index (RMDI) and EQ-5D, were collected at baseline, 1 week, 1-, 3-, and 6-months. Procedural technical outcomes were recorded and adverse events were evaluated at all follow-up intervals. METHODS: Oxygen-ozone treatment performed as outpatient day surgeries, included a one-time intradiscal injection delivered at a concentration of 35±3 µg/cc of oxygen-ozone by a calibrated delivery system. Discectomies performed as open microdiscectomy inpatient surgeries, were without spinal instrumentation, and not as subtotal microdiscectomies. Primary analyses with a non-inferiority margin of -1.94-point difference in 6-month cumulative weighted mean leg pain NRS scores were conducted using As-Treated (AT) and Intent-to-Treat (ITT) populations. In post hoc analyses, differences between treatment groups in improvement over baseline were compared at each follow-up visit, using baseline leg pain as a covariate. RESULTS: In the primary analysis, the overall 6-month difference between treatment groups in leg pain improvement using the AT population was -0.31 (SE, 0.84) points in favor of microdiscectomy and using the ITT population, the difference was 0.32 (SE, 0.88) points in favor of oxygen-ozone. The difference between oxygen-ozone and microdiscectomy did not exceed the non-inferiority 95% confidence lower limit of treatment difference in either the AT (95% lower limit, -1.72) or ITT (95% lower limit, -1.13) populations. Both treatments resulted in rapid and statistically significant improvements over baseline in leg pain, back pain, RMDI, and EQ-5D that persisted in follow-up. Between group differences were not significant for any outcomes. During 6-month follow-up, 71% (17 of 24) of patients receiving oxygen-ozone, avoided microdiscectomy. The mean procedure time for oxygen-ozone was significantly faster than microdiscectomy by 58 minutes (p<.0010) and the mean discharge time from procedure was significantly shorter for the oxygen-ozone procedure (4.3±2.9 hours vs. 44.2±29.9 hours, p<.001). No major adverse events occurred in either treatment group. CONCLUSIONS: Intradiscal oxygen-ozone chemonucleolysis for single-level lumbar disc herniations unresponsive to medical management, met the non-inferiority criteria to microdiscectomy on 6-month mean leg pain improvement. Both treatment groups achieved similar rapid significant clinical improvements that persisted and overall, 71% undergoing intradiscal oxygen-ozone were able to avoid surgery.

Automated nucleotomy and nucleolysis with ozone.

Lumbar and radicular pain due to HNP has been described since 1934. It is thought that the pain is caused by compression and by other local chemical mediators that are present in the area of interaction between the root and the disc.With the objective of treating patients suffering from this syndrome and with a percutaneous minimally invasive approach, we designed a mixed technique: percutaneous automated nucleotomy plus nucleolysis and periradicular infiltration with ozone.A retrospective study of 105 patients was conducted, including 60 men and 45 women with an average age of 43 years. All patients were treated with that technique between November 2006 and August 2008. Clinical follow-up of 15.2 months was provided by telephone, utilizing a modified Mac Nab scale. The results were as follows: 60% excellent, 22.8% good (82.8% success), 9.6% acceptable, 7.6% poor. From the eight patients that reported poor results, five were considered to have recurrent symptoms (4.8%), because they had initially shown a period of significant improvement post operatively. Morbidity was manifested by transient pain and muscle spasms in the post operative area (2.8%).We conclude that this new mixed technique, compared to automated percutaneous nucleotomy alone, may be more widely utilized by broadening the indications, with acceptable results.

Treatment of symptomatic lumbar spinal degenerative pathologies by means of combined conservative biochemical treatments.

Research in spine surgery has proposed new soft and less invasive techniques. These are the results of our experience with oxygen-ozone therapy, which we could experiment within the Italian National Health System over 3 years. A total of 1,920 patients were admitted on the basis of unselected enrolment because of lumbosciatic pain. Patients were divided into three groups: (A) Patients with degenerative disc disease and arthropathy: 509 (26.5%), (B) Patients with failed back surgery syndrome (FBSS): 1,027 (53.489%), and (C) Patients with pure herniated lumbar disc: 384 (20%). The rationale of the treatment for all these different pathologies we have taken into consideration is the biochemical mechanism by which they can engender pain and dysfunction. Treatment for group A: paravertebral injection and phleboclysis (two cycles of 6 sessions, one each 3 days) +endoscopic neurolysis. Treatment for group B: paravertebral injection and phleboclysis (two cycles of 6 sessions, one each 3 days) + endoscopic neurolysis with intradiscal procedure (named percutaneous peridurodiscolysis). Treatment for group C: paravertebral injection (two cycles of 6 sessions, one each 3 days) + percutaneous discolysis.The perceived quality of result for this minimally invasive procedure makes oxygen-ozone therapy an interesting weapon in the hands of doctors. Furthermore, if the technique loses its clinical effectiveness, it can be repeated without harm for the patient, and costs for the health organization are notably very low, above all if compared to surgical procedures.We underline the need that this treatment should be performed in protected structures, in operative rooms, under anesthesiologic control, and in the hands of specialists.

Efficacy of Intradiscal Ozone Therapy with or without Periforaminal Steroid Injection on Lumbar Disc Herniation: A Double-Blinded Controlled Study.

BACKGROUND: Intradiscal ozone therapy, a minimally invasive technique, is used in patients that do not respond to standard conservative therapies for low back pain due to degenerative disc-induced lumbar disc herniation (LDH). Many studies on clinical efficacy lack a standardized injection method and are limited by inadequate study design. OBJECTIVE: This study aimed to determine the efficacy of periforaminal steroid injection together with intradiscal ozone therapy. STUDY DESIGN: A prospective, double-blinded, randomized controlled trial. SETTING: A tertiary care center. METHODS: This study was conducted in 65 patients with low back and leg pain caused by LDH. Group 1 received intradiscal ozone therapy (n = 35) and Group 2 received intradiscal ozone therapy with periforaminal steroid injection (n = 30). Patients were evaluated for pain using the visual analogue scale (VAS), for disability using Oswestry Disability Index (ODI), and for quality of life using the short form 36 health survey administered pre-injection and at one and 6 months post-injection. All procedures were performed under sterile conditions using C-arm fluoroscopy. RESULTS: Significant improvements were observed in pain, disability, and quality of life in both groups post-treatment compared to pre-injection. Mean pre-injection VAS was not significantly different between the groups (VAS: 7.8 ± 1.1 for Group 1, 7.8 ± 1.2 for Group 2). VAS values at 6 months for Group 1 and Group 2 were as follows: 3.6 ± 2.4, 4.1 ± 1.6, respectively) (P < 0.001). Mean pre-injection ODI was not significantly different between the groups (ODI: 20.9 ± 9.6 for Group 1, 25.2 ± 10.3 for Group 2). ODI values at 6 months for Group 1 and Group 2 were as follows: 12.8 ± 9.2, 14.3 ± 7.2, respectively) (P < 0.001). However, there were no significant differences between the groups. Similarly, there was no significant difference between the 2 groups on any of these parameters. LIMITATIONS: A limited number of patients and limited follow-up time. CONCLUSION: This study showed that intradiscal ozone injection alone was sufficient to treat low back and leg pain caused by LDH and that periforaminal steroid injection does not provide additional benefit, which is contrary to the literature.

Effects of laser irradiation on collagen organization in chemically induced degenerative annulus fibrosus of lumbar intervertebral disc.

BACKGROUND AND OBJECTIVE: The number of in vitro experimental studies was carried out with the use of intact tissues to establish a mechanism of laser-tissue interaction. However, in the process of degeneration, both biochemical composition and behavior of the disc were altered drastically. The objective of this study was to evaluate the role of the main matrix components in laser modification of annulus fibrosus (AF) under IR laser irradiation. STUDY DESIGNS/MATERIALS AND METHODS: The samples of AF in a motion segment after hyaluronidase treatment, trypsin digestion and glycation by glyceraldehyde were heated in hydrothermal bath (95 degrees C, 2 min) or irradiated by laser at 1.56 microm. Specimens were imaged by cross-polarization optical coherence tomography (CP-OCT), and then analyzed by differential scanning calorimery (DSC). RESULTS AND DISCUSSION: According to CP-OCT and DSC data non-significant alteration was revealed in AF after hyaluronidase treatment, glycation led to stabilization of annulus collagen and trypsin digestion resulted in a noticeable impairment of collagen fibrils. Laser treatment induced subsequent damages of AF matrix but these damages cannot be explained by laser heating only. The specificity of chemical modification of AF matrix has an influence on a character of collagen network alteration due to IR laser effect. Minimal and maximal alterations are observed for hyaluronidase and trypsin treated samples respectively. Glyceraldehyde fixed samples showed failure of the collagen structure after moderate laser treatment; at the same time thermal denaturation of collagen macromolecules was negligible. We assume that a mechanical effect of laser irradiation plays an important role in laser-induced annulus collagen modification and propose the scheme of physico-chemical process occurring under non-uniform IR laser treatment in AF tissue. CONCLUSION: CP-OCT and DSC techniques allow us to record the alteration of collagen network organization as a result of chemical modification. There were detected significant and specific effects of the biochemical composition and material properties on the response of AF collagen network on laser irradiation. The results go in accordance with our hypothesis that the primary effect of laser influence on collagen network under tension is the mechanical damage of collagen fiber.