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.

Immediate Effects, Detailed Clinical Outcomes, and Prognostic Factors of Chemonucleolysis Using Condoliase for Lumbar Disc Herniation.

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.

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.

Development process and clinical application of collagenase chemonucleolysis in the treatment of lumbar disc herniation: a narrative review in China.

Lumbar disc herniation (LDH) is one of the most common causes of lumbocrural pain. In the past 20 years, the incidence of LDH has increased dramatically. There are many treatments for LDH, including conservative treatment (such as acupuncture and physiotherapy), minimally invasive interventional treatment (such as collagenase chemonucleolysis and radiofrequency ablation) and surgical treatment. The main purpose of this paper is to review the development process and application status of collagenase chemonucleolysis in the treatment of LDH at home and abroad and provide a reference for clinical treatment.

Short-term clinical and radiographic outcomes of chemonucleolysis with condoliase for painful lumbar disc herniation and analysis regarding intradiscal injection area.

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.

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.

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.

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.

Factors Predicting Successful Outcome for Ozone Chemonucleolysis in Lumbar Disk Herniation.

OBJECTIVES: The aim of this study was to retrospectively investigate factors predicting a successful outcome after ozone chemonucleolysis (OCN) in patients with radicular pain and poor response to conservative treatments. METHODS: Univariable and multivariable logistic regression analysis was used to identify the predictors of good outcome after OCN. Good outcome was defined as 33% Oswestry Disability Index (ODI) reduction (model 1) or 13-point ODI improvement (model 2) at 1 month after OCN. RESULTS: Two hundred seventy-three patients were analyzed. A significant pain reduction (pre-operative Numerical Rating Scale [NRS] 6.7 ± 1.5, postoperative NRS 2.6 ± 2.2, P < 0.0001) and ODI improvement (pre-operative ODI 39 ± 13.7, postoperative ODI 21.4 ± 13.8, P < 0.0001) was obtained 1 month after OCN. Pain duration (< 1 year), type of disk herniation based on Michigan State University classification (MSU), stages of disk degeneration revealed by discogram and absence of foraminal stenosis (bony or ligament flavum hypertrophy) appeared as predictors of successful outcome. Age, gender, previous spine surgery, level site of disk herniation, presence of uncontained lumbar disk herniation, and vertebral Modic changes were not statistically associated with the outcome. Both the models showed a good accuracy (model 1, area under the curve [AUC] = 0.84 ± 0.027, 95% confidence interval [CI] = 0.79 to 0.89; model 2, AUC = 0.86 ± 0.024, 95% CI = 0.81 to 0.91). CONCLUSIONS: OCN is an effective treatment for radicular pain due to disk herniation. Pain duration (< 1 year), MSU disk herniation type (1A, 1B, 1C, 2A, and 2B), disk degeneration grade 2, and absence of foraminal stenosis are all associated with the successful outcome and should be carefully evaluated before OCN.

Foot drop after percutaneous treatment with radiopaque gelified ethanol (Discogel®) / Pie caído posterior al tratamiento percutáneo con etanol gelificado radiopaco (Discogel®)

Sciatica due to a lumbar disc herniation is a frequent symptom, between 13% and 40% of the general population will experience an episode of sciatica during their lives. Different techniques exist to treat this condition. Among them the percutaneous intradiscal Discogel®. In all the series of patients reviewed treated with Discogel®, so far, there is not any case reported with disc extrusion and significant neurological damage. We present a case of a foot drop, caused by a disc herniation after percutaneous treatment with Discogel®. We hypothesize that the pathogenic mechanism would be the increased intradiscal volume and pressure post-puncture and annulus fibrosus damage, which could produce the disc extrusion. The extrusion of Discogel® material is possible. To the best of our knowledge, this is the first reported case of this complication with this product (AU)

La ciática secundaria a una hernia discal lumbar es un síntoma frecuente; entre el 13% y el 40% de la población general experimentará un episodio de ciática durante sus vidas. Se han desarrollado diferentes técnicas para tratar esta dolencia. Entre ellas, el Discogel® intradiscal percutáneo. En todas las series revisadas de pacientes tratados con Discogel®, hasta el momento, no se ha informado ningún caso de extrusión discal ni daño neurológico importante. Presentamos un caso de pie caído, causado por una hernia de disco posterior al tratamiento percutáneo con Discogel®. Nuestro mecanismo teórico es el aumento del volumen y la presión intradiscal más el daño del anillo fibroso pospunción que podría producir una extrusión discal. La extrusión del material Discogel® es posible. Hasta donde sabemos, este es el primer caso reportado de esta complicación con este producto (AU)

The effectiveness of chemonucleolysis with condoliase for treatment of painful lumbar disc herniation.

BACKGROUND: Chemonucleolysis with condoliase, which degrades chondroitin sulfate, could be a new, minimally invasive therapeutic option for patients with lumbar disc herniation (LDH). The purpose of this study was to analyze prognostic factors for clinical outcomes in LDH patients subjected to chemonucleolysis with condoliase. METHODS: Inclusion criteria for this procedure were 1) 18-70 years of age; 2) unilateral leg pain and positive straight leg raise (SLR) (<70°) or femoral nerve stretching test; 3) subligamentous extrusion verified on magnetic resonance imaging; 4) neurological symptoms consistent with a compressed nerve root on magnetic resonance imaging (MRI) images; and 5) minimum six months of follow-up. In total, 82 patients (55 men, 27 women; mean age, 47.2 ± 15.5 years; mean follow-up, 9.1 ± 3.0 months) who underwent chemonucleolysis with condoliase for painful LDH were included. An improvement of 50% or more in the Visual analogue scale (VAS) of leg pain was classified as effective. RESULTS: Seventy patients (85.4%) were classified into the effective (E) group and 12 patients (14.6%) into the less-effective (L) group. Surgical treatment was required in four patients. No severe adverse complications were reported; 41.3% of the patients developed disc degeneration of Pfirrmann grade 1 or more at the injected disc level. Univariate analysis revealed that young age (p = 0.036), without history of epidural or nerve root block (p = 0.024), and injection into the central portion of the intervertebral disc (p = 0.014) were significantly associated with clinical effectiveness. A logistic regression analysis revealed that injection into the central portion of the intervertebral disc (p = 0.049; odds ratio, 4.913; 95% confidence interval, 1.006-26.204) was significantly associated with clinical effectiveness. CONCLUSIONS: Chemonucleolysis with condoliase is a safe and effective treatment for painful LDH; 85.4% of the patients showed improvement after the treatment without severe adverse events. To obtain the best outcome, condoliase should be injected into the center of the intervertebral disc.

Foot drop after percutaneous treatment with radiopaque gelified ethanol (Discogel®).

Sciatica due to a lumbar disc herniation is a frequent symptom, between 13% and 40% of the general population will experience an episode of sciatica during their lives. Different techniques exist to treat this condition. Among them the percutaneous intradiscal Discogel®. In all the series of patients reviewed treated with Discogel®, so far, there is not any case reported with disc extrusion and significant neurological damage. We present a case of a foot drop, caused by a disc herniation after percutaneous treatment with Discogel®. We hypothesize that the pathogenic mechanism would be the increased intradiscal volume and pressure post-puncture and annulus fibrosus damage, which could produce the disc extrusion. The extrusion of Discogel® material is possible. To the best of our knowledge, this is the first reported case of this complication with this product.

Chemonucleolysis with Chondroitin Sulfate ABC Endolyase for Treating Lumbar Disc Herniation: Exploration of Prognostic Factors for Good or Poor Clinical Outcomes.

Background and Objectives: Chondroitin sulfate ABC endolyase (condoliase) was launched as a new drug for chemonucleolysis in 2018. Few studies assessed its clinical outcomes, and many important factors remain unclear. This study aimed to clarify the preoperative conditions in which condoliase could be highly effective. Materials and Methods: Of 47 patients who received condoliase, 34 were enrolled in this study. The mean age of the patients was 33 years. The average duration since the onset of disease was 8.6 months. We evaluated patients' low back and leg pain using a numerical rating scale (NRS) score at two time points (before therapy and 3 months after therapy). We divided the patients into two groups (good group (G): NRS score improvement ≥ 50%, poor group (P): NRS score improvement < 50%). The parameters evaluated were age, disease duration, body mass index (BMI), and positive or negative straight leg raising test results. In addition, the loss of disc height and preoperative radiological findings were evaluated. Results: In terms of low back and leg pain, the G group included 9/34 (26.5%) and 21/34 (61.8%) patients, respectively. Patients' age (low back pain G/P, 21/36.5 years) was significantly lower in the G group for low back pain (p = 0.001). High-intensity change in the protruded nucleus pulposus (NP) and spinal canal occupancy by the NP ≥ 40% were significantly high in those with leg pain in the G groups (14/21, p = 0.04; and 13/21, p = 0.03, respectively). Conclusions: The efficacy of improvement in leg pain was significantly correlated with high-intensity change and size of the protruded NP. Condoliase was not significantly effective for low back pain but could have an effect on younger patients.

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.

Selective Chemonucleolysis With Condoliase in Cynomolgus Monkeys.

Selective chemonucleolytic effects of condoliase, a glycosaminoglycan degrading enzyme, was investigated histopathologically in cynomolgus monkeys. Condoliase was administered once into the lumber intervertebral disc (IVD), and as a comparative control, chymopapain, a proteolytic enzyme, was administered in a similar manner. Histopathological changes of the IVD and the adjacent vertebral body (VB) were examined at 1 to 26 weeks after administration. Major changes induced by condoliase in the IVD were degenerative and necrotic changes in the nucleus pulposus, annulus fibrosus, cartilaginous endplate (CEP), and epiphyseal growth plate (EGP); focal disappearance of the EGP; and neovascularization and ossification of the CEP. Decreased/necrosis of bone marrow cells with new bone formation was observed in the VB. Cellular regeneration in the IVD was observed as a recovery changes on and after week 4. The changes in the IVD and VB subsided at week 26. Chymopapain induced qualitatively similar but more widely extended changes. The degrees of the changes in the IVD and VB were more severe than those of condoliase, and the changes were exacerbated even at week 26. These results indicated that histopathological changes caused by condoliase were less severe and more selective than those by chymopapain.

Técnicas abandonadas en cirugía de columna / Abandoned techniques in spine surgery

En cirugía de columna, ciertos dispositivos y algunas técnicas quirúrgicas han sido abandonados por completo o se hallan en franco declive. Aunque empleados en miles de pacientes, dichos tratamientos no han demostrado una efectividad sólida y duradera y, ocasionalmente, asocian morbilidades inaceptables. Ejemplos de abandono son la quimionucleólisis, la discectomía percutánea, la discectomía por láser o los geles antifibrosis. Otras técnicas se encuentran en marcado retroceso como los dispositivos interespinosos o las prótesis discales lumbares. Generalmente una técnica se abandona por falta de efectividad, morbilidad excesiva, sustitución por otra técnica más eficaz y menos agresiva, por falta de comercialización o por prohibición de su uso. En las últimas décadas, la enorme presión comercial y una creciente demanda social han conseguido convencer a muchos cirujanos de columna para que empleen tratamientos no suficientemente sustentados por estudios sólidos ni avalados por el paso del tiempo, muchos de los cuales eventualmente se abandonan

In spine surgery, certain surgical techniques and devices are currently in marked decline or have been completely abandoned. Although used in thousands of patients, such treatments failed to demonstrate durable and sound effectiveness, and sometimes associate inacceptable morbidity. Chemopapain injections, percutaneous discectomy, laser discectomy or antiadhesion gels are examples of abandoned therapies. Some other techniques are in frank decline like implantation of interspinous devices or lumbar disc prosthesis. In general, a technique is abandoned due to inefficacy, excessive associated morbidity, substituted by another more efficacious and less aggressive technique, end of commercialization, or usage prohibition. In the last decades, a great commercial pressure plus an increasing social demand have managed to convince many spine surgeons to indicate treatments not sufficiently supported by scientific evidence nor consolidated over time, many of which are eventually abandoned

Evaluation of intervertebral disc using T2 mapping sequences in patients undergoing O2-O3 chemiodiscolysis: an instrumental study with clinical correlation.

PURPOSE: To assess the MRI modifications of the intervertebral disc (IVD) treated by chemiodiscolysis using T2 mapping sequences. METHODS: Thirty sciatica patients (17 males, 13 females, mean age 47.52 years) were enrolled for percutaneous CT-guided O2-O3 chemiodiscolysis treatment. As a control group, we enrolled 30 patients who were treated by CT-guided periradicular injections. All patients were submitted to clinical (using VAS and Oswestry Disability index (ODI)) and imaging studies to evaluate the intervertebral disc area (IDA) and T2 mapping values of the IVD before and at 1-month follow-up. RESULTS: In the study group, pre-treatment IDA mean values were 20.47 ± 1.62 cm2, with significant reduction at the follow-up (P < 0.05). Mean pre-treatment T2 relaxation time values were 38.80 ± 4.51 ms, 44.05 ± 0.91 ms, and 45.45 ± 14.11 ms for anterior annulus fibrosus, nucleus pulposus (NP), and posterior annulus fibrosus, respectively, with significant increase at the level of the NP (P < 0.05) at the follow-up. Mean pre-treatment ODI and VAS scores were 21.5 ± 10.6 and 8.5 ± 0.57, with significant improvement at the post-treatment follow-up (P < 0.05). In the control group, despite clinical improvement, we did not find significant IVA reduction nor significant T2 values change after treatment. Correlation analysis of T2 mapping relaxation time values showed significant correlation of NP T2 mapping value with both the reduction of IDA (0.81, P < 0.001) and the improvement of VAS and ODI scores (0.86, P < 0.001) at 1 month. In the control group, we did not find any statistically significant correlation. CONCLUSIONS: T2 mapping may be a useful indicator to predict disc shrinkage and the clinical response to CT-guided O2-O3 injection.

Condoliase for treatment of lumbar disc herniation.

Lumbar disc herniation (LDH) is generally treated with a conservative therapy, and surgery is the only therapeutic option currently available for patients unresponsive to the conservative therapy. In the 1980s, chemonucleolysis with chymopapain, a protease, was widely used as the intermediate treatment between conservative therapy and surgical therapy in the Western countries. However, since chymopapain was withdrawn from the market in 2002 for non-scientific commercial reasons, chemonucleolysis has not been a therapeutic option for LDH. Condoliase (chondroitin sulfate ABC endolyase), a glycosaminoglycan-degrading enzyme, was approved by the drug regulatory authority in Japan as a newer intradiscal therapy for LDH after clinical studies conducted in Japan demonstrated efficacy and safety for patients with LDH. This review will focus on the preclinical pharmacology, pharmacokinetics, efficacy and safety of condoliase as a new option for treatment of LDH.