Cervical intervertebral disc herniation is a common condition and most often presents as neck or upper limb pain causing varying levels of disability and dysfunction. Percutaneous injection of ozone into the intradiscal space is a novel and minimally invasive technique for managing this condition and can be an effective alternative to surgical management. A literature search was done using the keywords ozone disc nucleolysis of cervical intervertebral lesions, and five studies were selected based on the inclusion and exclusion criteria. Meta-analysis was performed to determine safety, effectiveness, and symptomatic relief (determined based on the visual analog scale (VAS)) with the publication bias being removed. Subjects treated with ozone therapy showed significant reduction (p < 0.0001) in VAS score as compared to baseline VAS score with a standardized mean difference of 2.78 (95% CI = 1.48 to 4.07; Z value = 4.20). Ozone nucleolysis is a minimally invasive, relatively safe, and optimally effective treatment option for reducing the pain related to cervical disc. Intradiscal ozone therapy can be considered an alternative treatment modality, and well-designed, randomized clinical trials are required to confirm the long-term superiority of ozone therapy against other treatment modalities available for cervical disc herniation.

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.

The detailed changes in disc properties after intradiscal injection of condoliase remain controversial. At 3 and 9 months after administration, radiographic changes in discs were investigated. A total of 41 patients (men, 25; median age, 46 years) who underwent regular follow-up magnetic resonance imaging at 3 and 9 months after administration without additional invasive therapy were retrospectively investigated. The intensity changes of the nucleus pulposus based on the Pfirrmann disc grading system, midsagittal disc height, and maximum protrusion length of herniation were assessed. In addition, disc height changes were compared between 24 patients aged <50 years (young group) and 17 patients aged ≥50 years (over 50s group). The overall mean disc heights were 9.1, 7.5, and 7.6 mm preoperatively, at 3 months, and at 9 months, respectively, with a significant reduction at 3 months (P < 0.001) and no significant changes thereafter. The mean maximum protrusion length of herniation significantly and gradually decreased. The overall proportions of Pfirrmann disc grades after administration were equivalent between 3 and 9 months. However, the recovery from Pfirrmann disc grades IV to III was confirmed in 8 of 17 cases (47.1%) between 3 and 9 months, whereas 6 of 20 cases (30.0%) showed a decline from III to IV. Patients in the young group with pretreatment disc height >11 mm had the greatest reduction in disc height than the over 50s group. In conclusion, the clinical outcomes in the over 50s group were comparable to those in the young group after injection of condoliase, whereas young patients with higher disc were more susceptible to disc height reduction.

Chemonucleolysis utilizing condoliase is a minimally invasive treatment for lumbar disc herniation (LDH) aimed at reducing intervertebral disc pressure and enhancing symptoms. In this study, lower limb pain was measured using the numeric rating scale (NRS) the day after treatment and 1 and 3 months after treatment. Prognostic factors were assessed, categorizing participants into an improvement group (I-group) for NRS lower limb pain scores of ≥3.5 and a non-improvement group (N-group) for scores of <3.5. This study included a total of 225 patients treated between April 2020 and March 2023. The mean age was 46.5 ± 16.5 years, with 151 males. The mean duration of illness was 6.2 ± 8.52 months. As of the day after treatment, 60 cases were classified into the I-group, 118 cases at 1 month after surgery, and 152 cases at 3 months after surgery. The disease duration before treatment was significantly shorter in the I-group at 1 (8.19 ± 8.74 [I-group] vs. 5.17 ± 8.04 [N-group] months) and 3 months (8.51 [I-group] ± 7.35 vs. 5.69 ± 8.87[N-group] months) after treatment. The comparison of baseline leg pain NRS shows a difference in leg pain NRS in the I-group when compared on the day after treatment (6.02 ± 2.64 [I-group] vs. 7.50 ± 1.79 [N-group]), 1 (5.13 ± 2.69 [I-group] vs. 7.58 ± 1.66 [N-group]), and 3 months (4.42 ± 2.70 [I-group] vs. 7.34 ± 1.77 [N-group]). Chemonucleolysis using condoliase for LDH can improve symptoms the day after treatment and can be a minimally invasive treatment to avoid surgery.

UNASSIGNED: Condoliase-based chemonucleolysis is a minimally invasive intermediate treatment option between conservative approaches and surgical interventions for lumbar disk herniation (LDH). In this study, the effects of psychological factors on the clinical outcomes of condoliase therapy for LDH were assessed.
UNASSIGNED: This study involved patients with LDH who received condoliase injections over a 1-year follow-up period. Data from the visual analog scale (VAS) scores for leg and back pain, Oswestry Disability Index, and Hospital Anxiety and Depression Scale (HADS), which was utilized for the psychological assessment, were collected. Using magnetic resonance imaging, changes in disk height and degeneration were evaluated. Data were assessed at baseline and 1-month, 3-month, and 1-year follow-ups. Condoliase therapy was considered effective in patients whose VAS score for leg pain improved by ≥50% at 1 year from baseline and who did not require surgery. The patients were divided into two groups: those who reported effective treatment (Group E) and those who did not (Group I). Between these two groups, comparative analyses were carried out.
UNASSIGNED: In this study, a total of 102 patients (70 men; mean age, 43.8±18.2 years) were included. Condoliase therapy was effective in 76 patients (74.5%). Thirty-five patients (34.3%) showed psychological factors (HADS-Anxiety [HADS-A]≥8 or HADS-Depression [HADS-D]≥8) preoperatively and had a significantly lower rate of effectiveness than did those without psychological factors. Group I demonstrated significantly higher baseline back pain VAS, HADS, and HADS-D scores when compared with Group E. Logistic regression analysis identified females and the baseline HADS-D score as independent factors that were related to the effectiveness of condoliase therapy.
UNASSIGNED: The patients with psychological factors tended to experience residual pain resulting in adverse effects on the clinical outcomes of chemonucleolysis with condoliase.

UNASSIGNED: Condoliase is an enzyme used as a treatment for lumbar disc herniation (LDH). This enzyme degrades chondroitin sulfate (CS) in the nucleus pulposus of the intervertebral disc (IVD). However, there are cases in which symptoms do not improve, despite condoliase administration. This study reports histological analysis of lumbar disc tissue of LDH patients who underwent surgery because condoliase had no therapeutic effect.
UNASSIGNED: Between March 2019 and August 2019, 12 LDH patients who underwent full endoscopic spine surgery (FESS) discectomy at the Dezawa Akira PED Clinic were the subjects of the study. There are two study groups: six cases underwent FESS after condoliase administration, while six underwent FESS without condoliase administration. The average duration from drug administration to surgery was 152 days. Herniated disc removed at surgery was evaluated by histological staining including immunohistochemistry by anti-CS antibodies.
UNASSIGNED: Multiple large clusters (40-120 μm in diameter) were observed in the nucleus pulposus of those who received condoliase, but no clusters were observed in those who did not. The lumbar disc tissues, including the nucleus pulposus of recipients, were stained with anti-CS antibodies that recognize the CS unsaturated disaccharide, but non-administration tissue was not stained. These findings suggest that the enzyme acted on the nucleus pulposus, even in cases where symptoms were not improved by condoliase administration. Furthermore, there was no histological difference between stained images of the extracellular matrix in those who did or did not receive condoliase, suggesting that condoliase acted specifically on CS in the nucleus pulposus.
UNASSIGNED: We demonstrated that CS in the nucleus pulposus was degraded in patients in whom condoliase did not have a therapeutic effect. Moreover, condoliase acts in human IVD without causing necrosis of chondrocytes and surrounding tissues.

Background: Chemonucleolysis is a minimally invasive treatment of lumbar disc herniation (LDH). However, the low specificity of the enzyme and the existence of serious adverse events limit the application of chemonucleolysis. Clinical studies in recent years have shown that Chondroitin sulfate ABC endolyase (condoliase) is a potential therapeutic enzyme for LDH. Aim. A meta-analysis was conducted to determine the efficacy and safety of condoliase in LDH treatment. Methods: We searched Web of Science, Embase, PubMed, and Cochrane Library databases. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. The outcomes were the total effective rate, Oswestry Disability Index (ODI) score change, the proportion of lumbar surgery after condoliase treatment, herniated mass volume change, Pfirrmann grade change, and adverse events. Review Manager 5.3 and Stata 12.0 were used for meta-, sensitivity, and bias analysis. Results: Ten studies were included. A single-arm meta-analysis showed that the total effective rate was 78% [95% confidence interval (CI) 75%-81%], the proportion of surgery was 9% (95% CI 7%-12%), the proportion of Pfirrmann grade change was 43% (95%CI 38%-47%), and the adverse events were 4% (95% CI 2%-6%) after condoliase treatment. The two-arm meta-analysis showed that the ODI score change [standardized mean difference (SMD) -2.46, 95% CI -3.30 to -1.63] and the herniated mass volume change (SMD -16.97, 95% CI -23.92 to -10.03) of the condoliase treatment group were greater than those of the placebo control group, and there was no difference in adverse events between the two groups (OR 1.52, 95% CI 0.60-3.85). The results of sensitivity and publication bias analyses showed that the results were robust. Conclusion: Condoliase intradiscal injection has excellent eutherapeutic and safety for LDH, thus, has considerable potential as a treatment option besides conservative treatment and surgical intervention for LDH. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375492, PROSPERO (CRD42022375492).

Percutaneous chemonucleolysis with condoliase has been available for painful lumbar disc herniation since 2018 in Japan. This study investigated clinical and radiographic outcomes three months after the administration because the secondary surgical removal is most required during this period for the insufficient pain relief, and analyzed whether the differences of intradiscal injection areas affected the clinical outcomes. We retrospectively investigated 47 consecutive patients (males, 31; median age, 40 years) three months after the administration. Clinical outcomes were evaluated using the Japanese Orthopaedic Association Back Pain Questionnaire (JOABPEQ), a visual analog scale (VAS) score for low back pain, and VAS scores for pains and numbness in the lower limbs. Radiographic outcomes were analyzed in 41 patients, using parameters such as mid-sagittal disc height and maximal protrusion length of herniation on MRI preoperatively and at the final follow-up. Postoperative median evaluation period was 90 days. The effective rate of low back pain based on the pain-related disorders at baseline and the last follow-up in the JOABPEQ reached 79.5%. The postoperative proportion of VAS scores recovery ≥ 2 points and ≥ 50% for pains in the lower limbs were 80.9% and 66.0%, respectively, revealing satisfactory effectiveness. Preoperative median mid-sagittal disc height significantly reduced from 9.5 to 7.6 mm postoperatively. There were no significant differences in pain relief in the lower limbs by injection areas in the center and the dorsal 1/3rd near the herniation of nucleus pulposus. Chemonucleolysis with condoliase revealed satisfactory short-term outcomes after the administration regardless of intradiscal injection areas.

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.

BACKGROUND: Condoliase-induced chemonucleolysis is a less invasive treatment for lumbar disc herniation (LDH); however, its long-term clinical outcomes remain unclear. We investigated 2-year clinical outcomes and assess radiographs after chemonucleolysis with condoliase.
METHODS: We enrolled patients with LDH who received condoliase therapy, with a minimum follow-up period of two years. Sixty-seven patients (44 men, 23 women; mean age, 46.7 ± 18.0 years) were analyzed. Time-course changes in disc height, disc degeneration, and herniation size were assessed. For clinical outcomes assessment, visual analog scale (VAS) scores for leg and back pain and the Oswestry disability index (ODI) were obtained at baseline and the 3-month, 1-year, and 2-year follow-ups. We obtained a questionnaire from these patients at two years to assess satisfaction and recommendation. Condoliase therapy was considered to be effective in patients whose VAS score for leg pain improved by ≥ 50% at 2 years from baseline and who did not require surgery.
RESULTS: Condoliase therapy was effective in 51 patients (76.1%). Eight patients (11.9%) required surgery due to ineffectiveness of the therapy. Condoliase therapy was ineffective in five out of six patients with a history of discectomy. The ODI and VAS scores for leg and back pain significantly improved from three months to two years. Of the patients, 80% satisfied with their outcomes, and 85% recommended this therapy. Progression of disc degeneration was observed in 57.1% of patients at three months; however, 30% recovered to baseline at two years. The mean disc height decreased at three months, but recovered slightly at one year and remained stable until two years. No recurrent disc herniation was observed.
CONCLUSIONS: Chemonucleolysis with condoliase was effective in 78% of patients with LDH for 2 years. Chemonucleolysis-induced disc degeneration was slightly recovered and maintained for two years post-injection. This treatment resulted in high patient satisfaction and recommendations.