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ORIGINAL ARTICLE
Year : 2023 | Volume
: 14
| Issue : 1 | Page : 16-23
Ozone disc nucleolysis in the management of herniated lumbar intervertebral disc: A retrospective analysis
Sharad Balasaheb Ghatge1, Rohit Pannalal Shah2, Nirmal Surya3, Suresh Sankhala4, Chetan Jagjivandas Unadkat2, Gulam M Khan5, Dhaval B Modi6
1 Department of Radiology and Imaging, Division of Interventional Radiology, Grant Government Medical College and Sir JJ Group of Hospitals; Department of Interventional Neuroradiology, Bombay Hospital, Mumbai, Maharashtra, India
2 Department of Orthopedics, Breach Candy Hospital, Mumbai, Maharashtra, India
3 Department of Neurology, Bombay Hospital, Mumbai, Maharashtra, India
4 Department of Neurosurgery, Saifee Hospital, Mumbai, Maharashtra, India
5 Department of Neurosurgery, Global Hospital, Mumbai, Maharashtra, India
6 Department of Interventional Neuroradiology, Bombay Hospital, Mumbai, Maharashtra, India
Correspondence Address:
Sharad Balasaheb Ghatge
Flat No. 19, Swastik Building No. 4, Sir JJ Hospital Campus, Sir JJ Road, Byculla, Mumbai - 400 008, Maharashtra
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/jcvjs.jcvjs_141_22
Abstract
Background: Various minimally invasive surgeries were proposed for the management of herniated lumbar intervertebral disc. However, to choose optimal treatment modality to maximize patient benefit is a clinical challenge for the treatment givers.
Objective: The objective was to study the role of ozone disc nucleolysis in the management of herniated lumbar intervertebral disc by retrospective analysis.
Methodology: We conducted a retrospective analysis of patients of lumbar disc herniation treated by ozone disc nucleolysis during May 2007–May 2021. There were total of 2089 patients with 58% of males and 42% of females. The age ranged from 18 to 88 years. Outcome was measured on the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI) along with modified MacNab method.
Results: The mean baseline VAS score was 7.73, which became 3.07 at 1 month, 1.44 at 3 months, 1.42 at 6 months, and 1.36 at 1 year. Similarly, the mean ODI index was 35.92 at baseline, which improved to 9.17 at 1 month, 6.14 at 3 months, 6.10 at 6 months, and 6.09 at 1 year. VAS score and ODI analysis was found to be statistically significant with P < 0.05. Modified MacNab criterion showed successful treatment outcome in 85.6% with excellent recovery in 1161 (55.58%), good recovery in 423 (20.25%), and fair recovery in 204 (9.77%). Mediocre or no recovery was seen in the remaining 301 patients amounting to a 14.40% failure rate.
Conclusion: This retrospective analysis confirms that ozone disc nucleolysis is an optimally effective and least invasive treatment option for herniated lumbar intervertebral disc with a significant reduction in disability.
Keywords: Lumbar intervertebral disc herniation, ozone disc nucleolysis, ozone therapy
Introduction 
Low back pain (LBP) is the leading cause of years loss in disability (YLDs) worldwide.[1] The lifetime prevalence of LBP in the general population is between 60% and 85%.[2] Approximately 15% of cases of back pain are due to herniated discs. Conservative management with best rest, medications, and physical therapy is the most sought-after remedial measure. However, approximately 37%–58% of patients may not recover even after 12 weeks of conservative treatment. Ozone disc nucleolysis, laser, radiofrequency, or thermocoagulation-mediated percutaneous disc decompression are some of the recommended minimally invasive treatment modalities. Microsurgical decompression should be considered the last treatment option.[3],[4],[5] Failed back surgery syndrome, with a reported incidence of 10%–40% in various studies, remains a great challenge.[6] Ozone disc nucleolysis encompasses disc decompression along with nullifying the biochemical processes attributed to radiculopathy. This study reports a retrospective analysis on consecutive lumbar disc herniation patients treated by ozone disc nucleolysis.
Methodology We conducted a retrospective analysis of consecutive patients of lumbar disc herniation treated by a single session of intradiscal injection of ozone–oxygen mixture (ozone disc nucleolysis) during May 2007 to May 2021. There were total of 2089 patients with 58% of males and 42% of females. The age ranged from 18 to 88 years, with a mean of 60. Patients were selected based on inclusion and exclusion criteria, as stated below.
Inclusion criterion
Lumbosacral radicular pain concurring with magnetic resonance imaging (MRI) evidence of intervertebral disc herniationVisual Analog Scale (VAS) score ≥6Numbness along the dermatomal distribution corresponding to herniated disc as seen on MRIFunctional disability due to low backache with or without radiating painPatient willingness.Exclusion criterion
Clinical evidence of motor deficit corresponding to herniated discPositive red flags for axial skeletal like infection, trauma, or malignancyPatient refusal.All consecutively selected patients based on the above inclusion and exclusion criterion had undergone clinical examination and MRI evaluation before ozone disc nucleolysis. Baseline VAS score and Oswestry Disability Index (ODI) were noted. VAS score involves a numerical scale of severity of pain from 0 to 10, where 0 is no pain and 10 is unbearable pain. ODI score includes 0–5 scoring for each of the ten activities of daily living.[7] The minimum score will be 0, and the maximum score will be 50 [Table 1]. The patients' score is depicted out of 50.
Clinical profile
We treated 3762 Lumbar disc herniations in 2089 patients. Affected disc distributions were L5-S1:1196, L4-5:1720, L3-4:680, and L2-3:166, as seen on pre-treatment MRI. 2082 the patients presented with LBP with radiculopathy. 4 patients had only radiculopathy, and 3 patients presented with only severe LBP. 1856 patients had paraesthesia. At least one disc level was corresponding to the dermatomal distribution of the pain and paraesthesia in each patient. 1673 patients had undergone treatment at two levels, and 64 patients had three levels. 10 patients had undergone four levels. The remaining 416 have undergone treatment for solitary disc herniation.
Patients were admitted for 1 day. Written informed consent was obtained. The procedure was performed in the cath lab (Artis Zee, Siemens, Erlangen, Germany) with a high-resolution plat panel c-arm. The procedure was performed with the patient in a prone position. Cranial angulation is given to the image receptor to bring the disc into a tangential plane with adjacent end plates parallel to each other. This way, all the discs between L1 and S1 could be treated. Their lateral angulation is given ipsilateral to the symptomatic side so that the inferior facet of the superior vertebra comes to lie in the center of the intervertebral disc. A needle is inserted through the skin in a paraspinal region just lateral to the inferior facet of the superior vertebra directed toward the center of the intervertebral disc transforaminally [Figure 1]a. Local anesthesia is given along the needle track. 22G needle (Top Spinal Needle, Meditop Corporation, Malaysia) with a length of 17 cm was used. The position of the needle is checked with anteroposterior and lateral views [Figure 1]b and [Figure 1]c. Ozone was generated from medical-grade oxygen (Medical Ozonator, India). Thirty percent ozone–oxygen mixture was aspirated into a 10cc luer lock syringe through a 0.22-micron filter (Millipore Merck, Burlington, United States) and 3 ml injected intradiscally under fluoroscopic guidance. Then, the needle was pulled back into epidural space with 7 ml injected slowly over 1 min. Some of the ozone–oxygen mixtures get dispersed into surrounding soft tissues. Then 10-ml mixture of local anesthetic agent and corticosteroids (1% Lidocaine with 100 mg of hydrocortisone and 80 mg of triamcinolone) is injected in epidural space. If multiple levels are to be performed, then a 10-ml mixture is divided into equal parts.
Figure 1: (a) Cross-sectional drawing showing needle path (white arrow) along posterolateral approach. (b) Fluoroscopic image anteroposterior view showing needle in the disc (empty arrow). (c) Fluoroscopic image lateral view showing needle in the disc (empty arrow). (d) MRI axial image showing pretreatment disc herniation (slender arrow). (e) MRI axial image showing posttreatment disc resorption with healing of annulus (slender arrow). MRI – Magnetic resonance imagingAt the end of treatment, patients were advised to rest in a supine position for 2 h and then mobilized gradually over the next several hours. On discharge, patients were given supplementary medications and were instructed to resume their activities of daily living gradually. All the patients were advised to avoid heavy activities for 2–4 weeks, along with passive physiotherapy like interferential therapy, transcutaneous electrical nerve stimulation, ultrasound, and acupuncture as deemed appropriate. We would prefer active muscle-strengthening exercises after relief from pain. The outcome was assessed by the VAS score and ODI score at 1 month, 3 months, 6 months, and 1 year. The outcome was also assessed by the modified MacNab criterion [Table 2].
Statistical analysis
The data were entered and analyzed using the Statistical Package for the Social Sciences (SPSS) for Windows, version 28.0. (Armonk, NY, USA: IBM Corp). Confidence intervals (CIs) were set at 95%, and P ≤ of 0.05 was considered statistically significant. Repeat measures analysis of variance is used for analysis of baseline and follow-up data of VAS and ODI scores. Pair-wise comparisons of baseline data for VAS and ODI scores with follow-up data are compared using paired t-test.
Outcome
Recovery following ozone therapy was noted typically in three stages: (1) early stage: in most cases, immediate table complete or partial pain recovery. This recovery may last for a few days. Light activities with supplementary drugs are recommended. (2) Intermediate convalescence stage: in this stage, the benefit gained from the first stage might continue to progress or remain stagnant, or there may be a mild worsening of pain in the subsequent 2 weeks. Passive physiotherapy with lifestyle modification will hasten the further recovery. (3) Consolidation stage: this stage establishes improvement in the space of 6–8 weeks which is long lasting. Active core muscle-strengthening exercises will augment and maintain a symptom-free period. VAS and ODI scores were calculated on pretreatment clinical examination and compared with posttreatment scores. The modified MacNab method was used to assess clinical outcomes defining successful and failed treatment outcomes. Typically, clinical follow-up was done at 1 month, 6 months, and 1 year.
Results The mean VAS score at baseline was 7.73 which became 3.07 at 1 month, 1.44 at 3 months, 1.42 at 6 months, and 1.36 at 1 year. This was statistically significant with P < 0.05. Similarly, the mean ODI index was 35.92 at baseline, which improved to 9.17 at 1 month, 6.14 at 3 months, 6.10 at 6 months, and 6.09 at 1 year [Figure 2]. This was found to be significant with P < 0.05 [Table 3]. Modified MacNab criterion for outcome showed excellent recovery in 1161 (55.58%), good recovery in 423 (20.25%), and fair recovery in 204 (9.77%). Successful treatment comprising excellent, good, and fair recovery is seen in 1788 out of 2089 patients amounting to 85.6% success rate. Mediocre or no recovery was seen in the remaining 301 patients amounting to a 14.40% failure rate. There were no bad results seen. We could do 6 months postprocedure MRIs in 124 patients, of which 94 patients showed a reduction in disc herniation as compared to pretreatment MRI [Figure 1]d and [Figure 1]e.
Figure 2: (a) Outcome as per VAS over time. Baseline is pretreatment score and 1 month, 3 months, 6 months, and 1 year are posttreatment scores. (b) Outcome as per ODI score over time. Baseline is pretreatment score and 1 month, 3 months, 6 months, and 1 year are posttreatment scores. (c) Mean (95% CI) for VAS. (d) Mean (95% C.I.) for ODI. ODI – Oswestry Disability Index, CI – Confidence interval Discussion Ozone disc nucleolysis is fast emerging as the most promising and comprehensive minimally invasive treatment option for herniated lumbar intervertebral discs in the last two decades. As human beings were evolving from four-legged animals into two-legged erect civilized creatures, the entire weight bearing of the body fell onto the vertebral column, including intervertebral discs. Discs act as shock absorbers. They are made up of three components: the central nucleus pulposus surrounded by the rim of annulus fibrosus sandwiched between two cartilaginous end plates, which are firmly attached to adjacent vertebrae. The nucleus pulposus contains 65% proteoglycan and 20% collagen. The annulus contains a nearly inverse proportion of the same elements, which means 20% proteoglycan and 60% collagen. Ninety percent of the total volume of the nucleus pulposus is water, as against 60% in the annulus. The nucleus pulposus develops before the immune system, and a blood–nucleus barrier is a complex composition of physical and molecular factors. The annulus and cartilaginous end plates act as a physical barrier, and the Fas ligand, a membrane protein, makes the nucleus immune privileged. Proteoglycans can hold water and make it a pressurized fluid bag, exerting equal pressure on the annulus. Elastic fibers are present throughout the disk, which makes it adapt to loading and unloading throughout activities of daily living. Discs are avascular, and nutrition is by osmosis from the circulating blood in vertebral bodies via end plates. Sensory and perivascular sympathetic nerve fibers innervate them only in the outer layer of the annulus.[8]
Relative hypermobility of the cervical and lumbar vertebral segments adds insult to injury. Erect posture is maintained anteriorly by abdominal and thoracic muscles and posteriorly by the spinal extensors group of muscles. These two groups of muscles act as supporting strings opposing each other. A person's height determines the body's optimum weight, which also denotes the load-bearing capacity of the spine. When the load on the spine exceeds its capacity due to external impact, sudden jerky movements, or prolonged wrong posture, the brunt falls on the intervertebral disc. This may lead to intervertebral disc herniation in a posterior direction toward the spinal canal, the weakest path. There are three types of herniations described per severity and extent. A bulging disc is a diffuse displacement of the nucleus circumferentially exerting pressure on the weakened annulus. Protrusion denotes the herniation of the nucleus through the partial tear of the inner annulus, and the outer annulus covers the herniated nucleus.
Bulging and protruded disc herniations are also called contained herniation. Imaging-wise and morphologically, it is defined as when the base of protruded disc material is wider than its dome. In extrusion, there is a complete tear in the annulus through which nuclear material prolapses out of disc space. Extrusion is uncontained herniation. Imaging-wise and morphologically, it is when the base of the hernia is narrower than the dome.
Furthermore, extruded disc material may extend above or below the disc level, called cranial or caudal migration. Sequestration is an extrusion where the disc material gets separated from the rest of the parent disc. Disc herniations in the craniocaudal (vertical) direction through a break in the vertebral body end plate are referred to as intravertebral herniations or Schmorl's nodes.[8],[9] Reeling under the wear and tear of daily activities and the aging process, the annulus is constantly under strain which may accumulate micro fissures over a period of time. Four distinct scenarios will be unfolded depending on the impact and degenerative process. Bulging disc with the intact annulus, annular tear without protrusion, annular tear with protrusion and annular tear with extrusion.
Etiopathogenesis of herniated lumbar intervertebral disc
Herniated lumbar intervertebral discs are a well-recognized treatable cause for disabling LBP with or without radiating pain. Two different mechanisms are involved etiopathogenesis of symptomatology of herniated disc. First, it is the mechanical compression of the nerve root by a herniated intervertebral disc. Mild mechanical compression induces venous congestive nerve root edema, and severe compression results in arterial ischemia leading to sharp shooting pain along the dermatome.[10],[11] Mechanical compression is not the only factor responsible for all the symptoms. Ruptured disc nucleus herniates out through a tear in the annulus fibrosus exposing itself to immune system. This leads to recruitment of monocytes resulting in the chemotaxis of macrophages and angiogenesis. Subsequent lymphocyte activation with the secretion of interferon-γ (IFN γ) and macrophage recruitment lead to inflammatory peripheral radiculopathy. Inflammatory markers like interleukin-6 (IL-6), IL-12, and IFN-γ and CD68 macrophages are seen in greater quantity in the extruded disc. There are two types of macrophages seen in autoimmune-mediated inflammatory reactions. M1 macrophages produce pro-inflammatory cytokines, and M2 macrophages produce anti-inflammatory cytokines. Activation of M1 macrophages is followed by M2. However, this switch from M1 to M2 is unpredictable. M1-mediated pro-inflammatory phase may last longer, leading to prolonged and painful illness.[12] Tumor necrosis factor-α and phospholipase A2 in herniated nucleus pulposus are responsible for partial demyelination making it susceptible to mechanical pressure leading to neuropathic paresthesia and pain.[11] Thus, symptoms arising from disc herniation are due to the amalgamation of bio-chemical-mechanical factors.[11],[12],[13]
Ozone as a pharmaceutical drug
Medicinal ozone is generated from medical-grade oxygen by corona discharge. It is to be used judiciously as a pharmaceutical agent in prescribed doses. As stated by Viebhan, the therapeutic dose is 10–30 μg of ozone per milliliter of oxygen. It is found that at 25%–30% concentration ozone induces dehydration of the disc nucleus and inflammatory reactions. Most of the trials proved that a dose of 25%–27% ozone would be optimum for therapeutic effects in disc herniation.[14],[15],[16]
Mechanism of action of ozone disc nucleolysis in the treatment of herniated disc
The rationale for surgical treatment of disc herniation is a partial removal of the disc, which decreases mechanical compression and relieves the pain. Most of the minimally invasive modalities solely rely on removing disc material to reduce pressure on nerve roots. The principle mechanism of action underlined in these procedures is that a small volume change produces a large change in pressure.[17] As stated by Murphy et al., ozone involves in fragmentation of glycosaminoglycans with water molecules leading to a small decrease in volume of nucleus with a significantly greater decrease in pressure resulting in the recoil of the nucleus and restoration of the intervertebral disc.[18] This is the predominant action of ozone in contained discs because the nucleus pulpous is protected within the disc by the Fas ligand. In uncontained discs, immune privileged nucleus is exposed to the host immune system with antibody-mediated inflammatory reactions. Ozone in the epidural space facilitates the switch from M1 to M2 macrophages transforming inflammatory phase to a reparative phase.[12] Ozone is also implicated in regenerating myelin sheaths.[19],[20] Thus, ozone disc nucleolysis can simultaneously act by mechanical decompression and immune modulation. The surgical treatment and other minimally invasive treatment options can relieve only mechanical compression. Epidural steroid injections will only have an anti-inflammatory effect. MRI studies 6 months postozone disc nucleolysis show disc volume reduction in 60%–70% of cases though clinical recovery precedes the imaging recovery. Judicious selection of patients is of paramount importance for successful outcome. The success rate in our study is 85.6%, which is comparable to or even better than the published reports.[3],[4],[5],[11] Radiological improvement was seen on follow-up MRI scans in those subsets of patients who agreed to the same. Clinical and radiological improvement is more satisfying for patients and treatment givers.[21] Complications related to ozone disc nucleolysis are very rare. Complications can be transient or permanent. Transient adverse events such as paresthesia, headache, syncope, and visual disturbances are common and almost completely recover in a few hours. Our series did not report any permanent disability over the last 15 years. The reported incidence of complications is approximately 0.1%.[13],[22],[23] Few very rare complications such as air embolism, vitreoretinal hemorrhage, pneumoencephaly, pneumomediastinum, cardiopulmonary arrest, and vertebrobasilar stroke are reported in literature.[24],[25],[26],[27],[28] However, these later complications are due to inadvertent injection of a large quantity of ozone–oxygen mixture leading to enormous increase in epidural pressure. Optimization dose of ozone injection will minimize these complications to almost nil. We recommend a maximum of 3 ml in the intradiscal space of the lumbar region. The drawback of this study is its retrospective analysis. Nevertheless, this study points out the benefit of ozone disc nucleolysis in the following patients. Patients with back pain radiating to lower extremity with imaging evidence of corresponding disc herniation not responding to conservative management. Patients with only back without radiculopathy can also be included. Some patients who presented with hypoesthesia along the dermatomal distribution corresponding to disc involvement will also benefit. Patients with severe motor deficits with or without the involvement of the urinary bladder and bowel should not be given this treatment choice and immediately be referred to surgical faculty for further management.
Conclusion Ozone disc nucleolysis is an optimally effective and least invasive treatment option for herniated lumbar intervertebral disc. Judicious selection of patients along with lifestyle modifications will lead to permanent cure. It is the only treatment modality which acts by mechanical decompression along with immune modulation neutralizing the inflammatory processes responsible for radiculopathy. Due to the negligible complication rate, ozone disc nucleolysis stands out among all minimally invasive procedures. Its results are comparable to surgery in the patients with no neurological deficit. This retrospective analysis suggests that ozone disc nucleolysis should be considered treatment of choice for the patients after failed conservative management. However, further studies with randomized control trials are warranted.
Acknowledgment
We would like to sincerely thank professor Dr. Jhunjhunwala, Head of the Department of Orthopedics, Bombay Hospital, Mumbai, India, for his constant support and guidance during this study.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References 
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