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.

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.

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.

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.

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.

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.

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.

Efficacy of an ethyl alcohol gel in symptomatic disc herniation.

PURPOSE: To evaluate the clinical outcome of DiscoGel® chemonucleolysis for symptomatic disc herniation in patients who fail conservative treatment. MATERIAL AND METHODS: Consecutive patients with symptomatic disc herniation confirmed on MRI who failed conservative management for at least 6 months were included. Visual analogue scale (VAS), Oswestry Disability Index (ODI) scores, and analgesic use were recorded at baseline, and 12 months after treatment. Multidetector CT (MDCT) was performed at baseline, and 12 months after treatment to assess for DiscoGel® extravasation and alteration in treated disc volume. In a unique long-term subgroup analysis of 31 patients, telephonic follow-up was performed utilizing VAS and ODI parameters 7 years after the procedure. RESULTS: A total of 87 disc herniations were treated in 71 patients; majority (54%) were treated at L4/5 and L5/S1. VAS score of 8 before treatment was reduced to 3 at 12 months after treatment (p = 0.0001); ODI score of 51 before treatment was reduced to 15 at 12 months after treatment (p = 0.0001). Analgesic use of 70.4% was reduced to 29.6% after treatment. There were no symptomatic procedural complications; MDCT revealed 1 asymptomatic peri-neural DiscoGel® extravasation. In the 31 subjects that underwent telephonic follow-up the VAS and ODI parameters maintained their values without statistically significant differences when compared with the 12-month follow-up. CONCLUSION: Patients with symptomatic disc herniation who failed conservative treatment and were treated with DiscoGel® chemonucleolysis achieved significant gains in pain relief and reduced disability without symptomatic complication. DiscoGel® chemonucleolysis is a feasible, minimally invasive technique for treatment of symptomatic disc herniation.

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.

Six-Month Results of Cervical Intradiscal Oxygen-Ozone Mixture Therapy on Patients with Neck Pain: Preliminary Findings.

BACKGROUND: Numerous techniques have been developed for the treatment of disc herniation. Oxygen-ozone (O2-O3) mixture therapy is a minimally invasive percutaneous treatment for disc herniation. OBJECTIVE: The aim of the study is to investigate the 6-month efficacy and safety of O2-O3 mixture therapy in patients with cervical disc herniation (CDH) and chronic neck pain. STUDY DESIGN: This is a cross-sectional, single-center study. SETTING: The study was conducted from January 2012 to May 2016 on patients visiting Sakarya University Training and Research Hospital's pain clinic. METHODS: Each patient was evaluated before the procedure (baseline) and at 2 weeks (W2), 6 weeks (W6), and 6 months (M6) after the procedure using the visual analog scale (VAS) and the Oswestry Disability Index scores. RESULTS: A total of 44 patients with CDH underwent the same treatment with an O2-O3 mixture. Significant pain relief was observed compared with preoperative pain at W2, W6, and M6 according to patient self-evaluation (P = 0.01). The mean VAS score was 7.89 ± 1.13 before the procedure, 4.22 ± 1.62 at W2, 3.03 ± 1.66 at W6, and 2.27 ± 1.25 at the end of M6. No significant complications or side effects were reported during or after the procedure. LIMITATIONS: Our study was conducted retrospectively, which resulted in problems obtaining follow-up data. In addition, this study was performed in a small patient group. CONCLUSION: Based on our results, intradiscal injection of an O2-O3 mixture treatment showed a beneficial long-term effect. KEY WORDS: Cervical disc herniation, chemonucleolysis, injection, intradiscal, oxygen-ozone mixture, percutaneous treatment.

Acute prevertebral abscess secondary to intradiscal oxygen-ozone chemonucleolysis for treatment of a cervical disc herniation.

Objective We herein present a case involving a prevertebral abscess complicated by a spinal epidural abscess (SEA) secondary to intradiscal oxygen-ozone chemonucleolysis for treatment of a cervical disc herniation. Methods A 67-year-old woman with a history of intradiscal oxygen-ozone chemonucleolysis developed numbness and weakness in her right upper and bilateral lower extremities followed by urinary retention. Her symptoms did not respond to intravenous antibiotics alone. Magnetic resonance imaging of the cervical region revealed an extensive SEA anterior to the spinal cord, spinal cord myelopathy due to anterior compression by the lesion, and a prevertebral abscess extending from C2 to T1. She underwent surgical drainage and irrigation. Results The patient was successfully treated with surgical drainage and systemic antibiotic therapy without kyphosis. Streptococcus intermedius was detected within the abscess. All clinical symptoms except for the sensory deficit in the left leg were relieved. Conclusions The safety of intradiscal oxygen-ozone therapy requires further assessment. High-dose intravenous antibiotics should be initiated empirically at the earliest possible stage of prevertebral and epidural abscesses. Surgical drainage may be a rational treatment choice for patients with a prevertebral abscess complicated by an SEA and spinal cord myelopathy.

Long-term Clinical Effects of DiscoGel for Cervical Disc Herniation.

BACKGROUND: Radiopaque gelified ethanol (RGE; DiscoGel, Gelscom SAS, France) is used as a chemonucleolysis substance in treating intradiscal herniation, showing good results without complications. It has also been used in cervical disc herniations (CDHs), demonstrating the potential efficacy of this substance. OBJECTIVE: The aim of the study is to investigate the long-term effectiveness and safety of DiscoGel in patients with CDH and chronic neck pain. STUDY DESIGN: This is a cross-sectional, single-center study. SETTING: The study was conducted from November 2013 to May 2016 on patients visiting Sakarya University Training and Research Hospital's pain clinic . METHODS: Each patient was evaluated before the procedure (baseline) and at 1, 3, 6, and 12 months after the procedure, using the visual analog scale (VAS) score for pain, the Oswestry Disability Index score to measure degree of disability, and estimate quality of life for those with pain; this coincides with scores on the Neuropathic Pain Questionnaire (DN4) for differential diagnoses. RESULTS: Thirty-three patients with CDH underwent the same treatment with DiscoGel between November 2013 and May 2016. Significant pain relief was noted, as opposed to preoperative pain, at 1, 3, 6, and 12 months after the procedure according to each patient's self-evaluation (P = 0.01). Differences in VAS, ODI, and DN4 scores between 1, 3, 6, and 12 months with the same variables were not statistically significant. There were no complications with the procedure. LIMITATIONS: Our study was conducted retrospectively, which led to problems with long-term follow-up data. In addition, this study was performed with a small group of patients. CONCLUSIONS: RGE is a potential alternative to surgery for patients with pain at the cervical level. However, we concluded that more studies with longer follow-up intervals with RGE will be necessary for assessment of the technique's efficiency. KEY WORDS: Cervical pain, herniation, neuropathic pain, injection, DiscoGel, chemonucleolysis.

Condoliase for the Treatment of Lumbar Disc Herniation: A Randomized Controlled Trial.

STUDY DESIGN: A randomized, double-blind, placebo-controlled, multicenter phase III clinical trial. OBJECTIVE: To evaluate the efficacy and safety of chemonucleolysis with condoliase in patients with lumbar disc herniation (LDH). SUMMARY OF BACKGROUND DATA: Condoliase is a pure mucopolysaccharidase derived from a bacterium, Proteus vulgaris that has high substrate specificity for chondroitin sulfate and hyaluronic acid in the nucleus pulposus of the intervertebral disc. METHODS: In this study, patients aged 20 to 70 years with unilateral leg pain, positive straight leg raise test, and a contained LDH were recruited in Japan. Patients were treated with a single injection of condoliase (1.25 U) or placebo and were followed for 1 year after administration. The primary endpoint was change in worst leg pain from baseline to week 13. The secondary endpoints included responder rate, and the changes from baseline up to week 52 in the worst leg pain, worst back pain, Oswestry Disability Index, 36-Item Short-Form Health Survey, neurologic examinations, and imaging parameters. RESULTS: A total of 82 and 81 patients received an injection of condoliase and placebo, respectively. The average changes in worst leg pain from baseline to week 13 (primary endpoint) were -49.5 mm in the condoliase group and -34.3 mm in the placebo group, and the difference of -15.2 mm was significant (95% confidence interval, -24.2 to -6.2; P = 0.001). Significant improvements were observed in the condoliase groups, compared with the placebo group, in most secondary endpoints at 1 year after administration. In the condoliase group, back pain, Modic type 1 change, and decrease in disc height were frequently reported, without any clinically relevant consequences. CONCLUSION: Condoliase significantly improved symptoms in patients with LDH and was well tolerated. Condoliase is a novel and potent chemonucleolytic drug for the treatment of LDH. LEVEL OF EVIDENCE: 1.

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.

An Analysis of New Approaches and Drug Formulations for Treatment of Chronic Low Back Pain.

The prevalence of chronic low back pain (CLBP) is increasing. Treatment is effective in less than 50% of patients after 1 year. This review investigates new treatments for CLBP. An extensive literature review focuses on new treatments for CLBP. Their safety and efficacy were evaluated and are described in detail in this review. The investigation identified new treatments for CLBP including chemonucleolysis, platelet-rich plasma injections, artemin, tanezumab, and stem cells. Further research and innovation are needed to implement these methods into practice and assess clinical significance. The current evidence suggests that there are promising new agents for the treatment of CLBP.

MRI findings in lumbar spine following O2-O3 chemiodiscolysis: A long-term follow-up.

Intradiscal O2-O3 injections are conventionally used as a minimally invasive treatment for lumbar disc herniation in patients not responding to conservative treatments. The aim of the present study is to report data of long-term imaging follow-up (3 years) of patients treated with intradiscal O2-O3 lumbar chemiodiscolysis. We evaluated the changes of disc volume and the modifications in disc appearance (in terms of disc degeneration) and endplate changes (according to Modic), comparing the results with a control group of patients. Our results showed a stable reduction of the disc herniation volume in patients treated compared with the control group, while we did not find statistically significant differences in terms of disc degeneration and endplate changes (Modic). We concluded that the O2-O3 discolysis, despite leading to a significant shrinkage of the disc herniation, does not involve - in the long term - biomechanical changes of the spine in terms of acceleration of the disc degeneration process in comparison with the natural course.

Rational approach, technique and selection criteria treating lumbar disk herniations by oxygen-ozone therapy.

Radicular lumbar back pain is an important public health problem not yet benefiting from a unequivocal treatment approach. Medical and physical therapies represent the first solution; however, when these fail, the second therapeutic step is still controversial and mini-invasive treatments may play an important role. In these cases oxygen-ozone therapy has been proved to be a very safe and effective option that is widely used with different modalities. This paper, by reviewing oxygen-ozone therapy literature data, aims to describe the rationale of oxygen-ozone therapy for the treatment of lumbar disk herniations, propose an effective procedural technique and clarify patient selection criteria; furthermore, complications and follow-up management are also considered.

Longitudinal Comparison of Enzyme- and Laser-Treated Intervertebral Disc by MRI, X-Ray, and Histological Analyses Reveals Discrepancies in the Progression of Disc Degeneration: A Rabbit Study.

Regenerative medicine is considered an attractive prospect for the treatment of intervertebral disc (IVD) degeneration. To assess the efficacy of the regenerative approach, animal models of IVD degeneration are needed. Among these animal models, chemonucleolysis based on the enzymatic degradation of the Nucleus Pulposus (NP) is often used, but this technique remains far from the natural physiopathological process of IVD degeneration. Recently, we developed an innovative animal model of IVD degeneration based on the use of a laser beam. In the present study, this laser model was compared with the chemonucleolysis model in a longitudinal study in rabbits. The effects of the treatments were studied by MRI (T2-weighted signal intensity (T2wsi)), radiography (IVD height index), and histology (NP area and Boos' scoring). The results showed that both treatments induced a degeneration of the IVD with a decrease in IVD height and T2wsi as well as NP area and an increase in Boos' scoring. The enzyme treatment leads to a rapid and acute process of IVD degeneration. Conversely, laser radiation induced more progressive and less pronounced degeneration. It can be concluded that laser treatment provides an instrumental in vivo model of slowly evolving IVD degenerative disease that can be of preclinical relevance for assessing new prophylactic biological treatments of disc degeneration.

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.