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ORIGINAL ARTICLE
Year : 2022  |  Volume : 13  |  Issue : 2  |  Page : 114-120  

Ozone disc nucleolysis in cervical intervertebral disc herniation: A nonrandomized prospective analysis in 246 patients


1 Division of Interventional Radiology, Department Of Radiology and Imaging, Grant Government Medical College and Sir JJ Group of Hospitals; Department of Interventional Neuroradiology, Bombay Hospital, Mumbai, Maharashtra, India
2 Department of Orthopedic, Breach Candy Hospital, Mumbai, Maharashtra, India
3 Department 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

Date of Submission26-Mar-2022
Date of Acceptance08-May-2022
Date of Web Publication13-Jun-2022

Correspondence Address:
Sharad Balasaheb Ghatge
Flat No. 19, Swastik Building No. 4, Sir JJ Hospital Campus, Sir JJ Raod, Byculla, Mumbai - 400 008, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcvjs.jcvjs_46_22

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   Abstract 


Background: Inherent complications associated with surgery and limited success of percutaneous minimally invasive procedures make researches wanting for an ideal treatment for cervical disc herniation.
Objective: We prospectively study the role of ozone disc nucleolysis in cervical intervertebral disc herniation.
Patients and Methods: From January 2008 to December 2020, we prospectively study 246 consecutive patients of cervical disc herniation treated by a single session of intradiscal injection of ozone–oxygen mixture (ozone disc nucleolysis). There were 55% of females and 45% of males. Age ranged from 28 to 68 years with a mean of 47. The outcome was measured on visual analog scale (VAS) scale and neck disability index (NDI) along with Mcnab method.
Results: The mean baseline VAS score was 7.87 which became 3.09 at 1 month, 1.42 at 3 months, 1.40 at 6 months, and 1.35 at 1 year. The mean NDI was 36.27 at baseline which improved to 9.24 at 1 month, 6.25 at 3 months, 6.20 at 6 months, and 6.22 at 1 year. This was found to be significant with P < 0.05. Modified McNab criterion showed excellent recovery in 138 (56.10%), good recovery in 50 (20.32%), and fair recovery in 22 (8.94%), resulting in a successful rate of 85.36%. Mediocre recovery was seen in the remaining 36 patients amounting to a 14.64% failure rate.
Conclusion: This study showed that ozone disc nucleolysis significantly reduces the pain related to cervical disc herniation along with a significant reduction in disability.

Keywords: Cervical disc herniation, cervical radiculopathy, ozone disc nucleolysis


How to cite this article:
Ghatge SB, Shah RP, Surya N, sankhala S, Unadkat CJ, Khan GM, Modi DB. Ozone disc nucleolysis in cervical intervertebral disc herniation: A nonrandomized prospective analysis in 246 patients. J Craniovert Jun Spine 2022;13:114-20

How to cite this URL:
Ghatge SB, Shah RP, Surya N, sankhala S, Unadkat CJ, Khan GM, Modi DB. Ozone disc nucleolysis in cervical intervertebral disc herniation: A nonrandomized prospective analysis in 246 patients. J Craniovert Jun Spine [serial online] 2022 [cited 2022 Aug 9];13:114-20. Available from: https://www.jcvjs.com/text.asp?2022/13/2/114/347327




   Introduction Top


Neck pain with or without radiation to arm leads to disability and loss of man-hours.[1] Cervical disc herniation is a common cause of neck pain in adults. Its prevalence increases with age and is most often seen in the third to fifth decades of life. Occurrence is more frequent in females which accounts for approximately 60% of caseload.[2] Cervical disc herniation presents most commonly as a degenerative spine.[3] However, modern-day repetitive stress and traumatic injuries are emerging causes of it. Majority of patients recover by conservative management which includes rest, medications, and physical therapies. Close to 10%–25% of cases may require surgical interventions.[4] Inherent complications associated with cervical spine surgery in best of the hands makes minimally invasive procedures most sought after treatment modalities.[5] Etiopathogenesis not only involves mechanical compression, but it is due to amalgamation of bio-chemico-mechanical factors.[2],[6],[7] Most of the routinely available minimally invasive such as percutaneous lumbar discectomy, laser discectomy, percutaneous plasma disc decompression, intradiscal electrothermal therapy, and percutaneous intradiscal radiofrequency thermocoagulation are based on mechanical decompression.[6] Ozone disc nucleolysis is the only modality which not only does decompression but neutralizes the biochemical processes responsible for radiculopathy. We report a nonrandomized prospective study on consecutive patients affected by cervical disc herniation and treated by ozone disc nucleolysis.


   Patients and Methods Top


From January 2008 to December 2020, a total of 246 consecutive patients with cervical disc herniation were treated by a single session of intradiscal injection of ozone–oxygen mixture (ozone disc nucleolysis). There were 55% of females and 45% of males. Age ranged from 28 to 68 years with a mean of 47.

Inclusion criterion

  1. Cervical radicular pain concurring with magnetic resonance imaging (MRI) evidence of intervertebral disc herniation
  2. Visual analogue scale (VAS) score ≥6
  3. Numbness along the dermatomal distribution corresponding to disc herniation as seen on MRI
  4. Functional disability due to neck pain with or without radiating pain
  5. Patient willingness.


Exclusion criterion

  1. Clinical and/or MRI evidence of cervical myelopathy
  2. Positive red flags for axial skeletal trauma, infection, or malignancy
  3. Patient refusal.


On selecting with the above criterion, all patients had undergone clinical examination and MRI evaluation. Baseline VAS score and neck disability index (NDI) were noted. VAS score involves a numerical scale of severity of pain from 0 to 10 where 0 is no pain and 10 is agonizing pain. NDI score is a modified version of the Oswestry Disability Index and includes 0–5 scoring for each of 10 activities of daily living.[8] The minimum score was zero and the maximum score was 50. Patient score was depicted out of 50 [Table 1].
Table 1: Neck Disability Index

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Clinical profile: There were 324 cervical disc herniations treated in 246 patients. Affected disc distributions were C5 – 6:178, C6 – 7:83, C4 – 5:55, and C3 – 4:08, as seen on pretreatment MRI. Two hundred forty patients had neck pain with radiculopathy. Three patients had only radiculopathy and three patients presented with only severe neck pain. One hundred fifty-six patients had paresthesia. At least one disc level corresponded to the dermatomal distribution of the pain and paresthesia in each patient. Seventy patients had undergone treatment at two levels and four patients had three levels. The rest of the patients had solitary disc herniation.

Patients were admitted for 1 day. Written informed consent was obtained. The procedure was carried out in cath lab (Artis Zee, Siemens, Erlangen, Germany) with high-resolution plat panel c-arm. Procedure was performed with the patient in the supine position. The patient's neck is extended with a thin pillow under the interscapular region. Caudal angulation is given to the image receptor to bring the disc in a tangential plane with adjacent endplates parallel to each other. This way all discs between C2 and D1 could be treated. The approach is right anterolateral. The operator displaces carotid sheath laterally, and trachea- esophagus medially between the thumb and index finger of one hand. The needle is then inserted by other hand though the soft tissue window between carotid sheath and trachea-esophagus [Figure 1]a. Local anesthesia is not required in this location. 22G spinal needle (Top Spinal Needle. Meditop corporation, Malaysia) with a length of 3.5 inches was used. The needle tip is directed toward the center of the disc [Figure 1]b and [Figure 1]c. 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). 30% ozone–oxygen mixture is aspirated into 3cc Luer Lok syringe through 0.22 μ filter (Millipore Merck, Burlington, United States) and one-two milliliter injected intradiscally under fluoroscopic guidance. Some of the ozone–oxygen mixture gets dispersed into surrounding soft tissues. Steroid injection of triamcinolone 2 mL injected intramuscularly in the deltoid muscle of on the painful side.
Figure 1: (a) cross sectional drawing showing needle path (slender arrow),trachea (Solid black arrow), Esophagus (Empty black arrow), Right carotid sheath (white bordered black arrow), (b) Fluoroscopic image anteroposterior view showing needle in centre of the disc (empty arrow), (c) Fluoroscopic image lateral view showing needle in centre of the disc (empty arrow), (d) MRI sagittal image showing pre treatment disc herniation (slender arrow), (e) MRI sagittal image showing post treatment disc resorption with healing of annulus (slender arrow), (f) MRI axial image showing pre treatment disc herniation (Solid arrow), (g) MRI axial image showing post treatment disc resorption (Solid arrow)

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At the end of treatment, patients were advised to rest in the supine position for 2 h and then mobilized gradually over the next several hours. On discharge, patients were given supplementary medications and are instructed to gradually resume their activities daily living. All the patients were advised to avoid heavy activities for 2 to 4 weeks along with passive physiotherapy such as intereferential 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 VAS scale and NDI score at 1, 3, and 6 months and 1 year. The outcome was also assessed by the modified McNab criterion [Table 2].
Table 2: Modified MacNab criterion

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Data analysis

Statically analysis was done by one-way analysis of variance (ANOVA) test. The results were considered statistically significant if P < 0.05. Repeated-measures ANOVA was used for the analysis of baseline and follow-up data of VAS and NDI scores. Pairwise comparisons of baseline data for VAS and NDI scores with follow-up data were compared using paired t-test.


   Results Top


The mean baseline VAS score was 7.87, which became 3.09 at 1 month, 1.42 at 3 months, 1.40 at 6 months, and 1.35 at 1 year. This was significant with P < 0.05. Similarly, the mean NDI was 36.27 at baseline which improved to 9.24 at 1 month, 6.25 at 3 months, 6.20 at 6 months, and 6.22 at 1 year [Figure 2] and [Table 3]. This was found to be significant with P < 0.05. Modified McNab criterion for outcome showed excellent recovery in 138 (56.10%), good recovery in 50 (20.32%), and fair recovery in 22 (8.94%). Excellent, good, and fair recovery considered successful treatment is seen in 210 out of 246 patients (85.36%). Mediocre or no recovery was seen in the remaining 36 patients amounting to a 14.64% failure rate. There were no bad results seen. We could do 6-month postprocedure MRI in 12 patients, of which eight patients showed a reduction in disc herniation as compared to pretreatment MRI, as shown in [Figure 1]d, [Figure 1]e, [Figure 1]f, [Figure 1]g.
Figure 2: (a) Outcome as per VAS scale over time. Baseline is pre treatment score and 1 month, 3 months, 6 months and one year are post treatment scores, (b) Outcome as per Neck Disability Index score over time. Baseline is pre treatment score and 1 month, 3 months, 6 months and one year are post treatment scores, (c) Mean (95% C.I.) for VAS, (d) Mean (95% C.I.) for NDI I)

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Table 3: VAS and NDI scores

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   Discussion Top


Ozone disc nucleolysis with its multimodal capabilities is emerging as the most comprehensive and least invasive treatment modality for cervical disc herniations. Disc herniation may be contained such as disc bulge and disc protrusion or noncontained like disc extrusion and disc sequestration. The appropriate treatment of cervical disc herniation is a challenge as mechanical and biochemical factors are involved in the pathophysiology of this disease. Mechanical compression leads to a range of microvascular changes. Mild compression produces venous congestive nerve root edema, and severe compression results in arterial ischemia initiating root cry which sets off sharp shooting pain along the dermatome.[2],[7] When disc ruptures, the immune-privileged nucleus displaces through tear in the annulus fibrosus leading to direct exposure of the nucleus to our immune system which, in turn, triggers the release of inflammatory mediators. These inflammatory mediators recruit monocytes from the immune system resulting in the chemotaxis of macrophages and angiogenesis. Subsequent lymphocyte activation with the secretion of interferon-gamma (IFN γ) and macrophage recruitment lead to one unfavorable effect of inflammation of nerve roots and dorsal root ganglia. There is another favorable effect that helps in the resorption of extruded nucleus pulposus. However, this natural resorption is painful and slow phenomenon. Inflammatory markers such as interleukin-6 (IL-6), IL-12, IFN γ, and presence of CD68 macrophages have greater presence in extruded disc. There are two different types of macrophages seen in autoimmune-mediated inflammatory reactions. M1 macrophages produce pro-inflammatory cytokines, and M2 macrophages produce anti-inflammatory cytokines. There is always a sequence in that activation of M1 is followed by M2. However when and how activation of M1 switches to activation of M2 macrophages is unpredictable. M1-mediated pro-inflammatory phase may last longer, leading to prolonged and painful illness. These inflammatory cascades of reactions are responsible for inflammatory radiculopathy with radiating pain along the course of nerve downhill.[9] Tumor necrosis factor α and phospholipase A2 are present in significant amount in herniated nucleus pulposus. These are responsible for partial demyelination that increases nerve root sensitivity making them more susceptible to mechanical pressure.[7] The mechanical compression due to herniated disc then able to trigger hyperexcitability leading to neuropathic paresthesia and pain. Thus, symptoms arising from disc herniation are due to amalgamation of bio-chemico-mechanical factors.[2],[7],[9] Ozone disc nucleolysis involves the injection of oxygen–ozone mixture. This mixture exploits the biochemical properties of ozone. Medicinal ozone is generated from medical-grade oxygen by corona discharge. It is to be used judiciously as a pharmaceutical agent in prescribed doses. In general, the accepted therapeutic dose is 10–40 μg of ozone per ml of oxygen. At 10% ozone acts as immunomodulatory. At 25–30, it helps in dehydration of the disc nucleus. Outside this therapeutic window, ozone momentarily activates cellular reactions at 1% and will be cytotoxic above 40%. Most of the trials prove the concentration of Ozone at 25%–30% will be optimum for therapeutic effects in disc herniation.[10],[11],[12] Ozone acts differently at different concentrations in different tissues. Mechanisms of action of intradiscal ozone injection involve fragmentation of glycosaminoglycans which are abundantly present in nucleus pulposus with subsequent release of water molecules This leads to a small decrease in volume of nucleus with a significantly greater decrease in pressure resulting in recoil of nucleus and restoration of the intervertebral disc. This is applicable to contained discs where the nucleus pulpous is protected by the Fas ligand which prevents infiltration of immunocytes. Proteoglycans present in the annulus also limit the inflammatory reaction. Here, dehydration of the nucleus and cytokine-mediated repair of the annulus is more dominant reactions. In uncontained discs, the immune-privileged nucleus is exposed to the host immune system with antibody-mediated inflammatory reactions leading to resorption and remission of the extruded nucleus by phagocytosis and lysis. Reactions that occur inside the disc space differ from that occur outside. Moreover, in epidural space, ozone acts as anti-inflammatory agent modulating and hastening switch from M1 to M2 macrophages converting an inflammatory phase to a reparative phase.[9] Ozone is also implicated in the regeneration of myelin sheaths.[13] We know the pathogenesis of the symptoms involves mechanical compression along with biochemical reactions. Our treatment strategy should fight on these two fronts simultaneously to give the patient lasting relief. All the minimally invasive treatment options and surgical decompression can relieve only mechanical compression. Only ozone–oxygen mixture has the ability to neutralize the inflammatory processes responsible for chemical radiculopathy along with decompression by shrinkage of the herniated disc.

Patient selection is key to successful ozone disc nucleolysis, as seen this study. Neck pain and or radiculopathy corresponding to disc herniation without cervical cord compression are ideal candidates to be offered this treatment. The reasons for failure were large disc protrusions, calcified disc, and spinal canal stenosis due to nondiscal elements. We have seen younger patients were responding better to this treatment. Acute disc herniation had a better outcome than chronic degenerative disc disease. Various studies have reported the technique and effectiveness of ozone therapy for cervical disc herniation.[14],[15],[16],[17] The results are consistent and long lasting with the adaptation of lifestyle modifications. The results are comparable to the other minimally invasive procedures. It is only treatment modality which acts by mechanical decompression along with neutralizing the inflammatory processes implemented in radiculopathy.

Only right anterolateral approach is available for cervical discs as the left anterolateral is avoided to prevent injury to the esophagus. Complications related to ozone disc nucleolysis are very rare. The reported incidence is approximately 0.1%.[6],[18],[19] The most common are paresthesia, headache, syncope, and visual disturbances. These are transient events and almost complete recover in few hours. Air embolism, vitreoretinal hemorrhage, and pneumoencephaly are very rare.[20],[21] There is one case each of cardiopulmonary arrest and vertebrobasilar stroke developing after ozone–oxygen mixture injection has been reported.[22],[23] Recently, massive emphysema and pneumomediastinum have been reported.[24] However, we believe that these later complications are due to increased epidural pressure as a result of inadvertent injection of large quantity of ozone–oxygen mixture. Standardization of the quantity of ozone injection will minimize these complications to almost nil. We recommend a maximum of 3 ml in intradiscal space of the cervical disc. In our institutional experience, we did not encounter any permanent disability in the last 15 years.


   Conclusion Top


This study showed that ozone disc nucleolysis significantly reduces the pain related to cervical disc herniation. There is a significant reduction in disability during activities of daily living. It is cost-effective with a short recovery time leading to curtailing loss of man-hours. Ozone disc nucleolysis is minimally invasive, least risky, and optimally effective treatment option. We strongly recommend it for cervical disc herniation with radiculopathy with or without neck pain not responding to conservative management. However, randomized control trial with a large study population is recommended to further validate our results.

Acknowledgment

We would like to sincerely thank Dr. Deepak Langade, Professor and Head Department of Pharmacology, DY Patil University School of Medicine, Navi Mumbai, for doing blindfolded statistical analysis We also like to sincerely thank Professor Dr. Jhunjhunwala, Head of Department of Orthopedic, 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 Top

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Safiri S, Kolahi AA, Hoy D, Buchbinder R, Mansournia MA, Bettampadi D, et al. Global, regional, and national burden of neck pain in the general population, 1990-2017: Systematic analysis of the Global Burden of Disease Study 2017. BMJ 2020;368:m791.  Back to cited text no. 1
    
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Boden SD, McCowin PR, Davis DO, Dina TS, Mark AS, Wiesel S. Abnormal magnetic-resonance scans of the cervical spine in asymptomatic subjects. A prospective investigation. J Bone Joint Surg Am 1990;72:1178-84.  Back to cited text no. 3
    
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Caridi JM, Pumberger M, Hughes AP. Cervical radiculopathy: A review. HSS J 2011;7:265-72.  Back to cited text no. 4
    
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Erario ML, Croce E, Moviglia Brandolino MT, Moviglia G, Grangeat AM. Ozone as modulator of resorption and inflammatory response in extruded nucleus pulposus herniation. Revising Concepts. Int J Mol Sci 2021;22:9946.  Back to cited text no. 9
    
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Costanzo M, Cisterna B, Vella A, Cestari T, Covi V, Tabaracci G, et al. Low ozone concentrations stimulate cytoskeletal organization, mitochondrial activity and nuclear transcription. Eur J Histochem 2015;59:2515.  Back to cited text no. 11
    
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Madrid Declaration on Ozone Therapy. International Meeting of Ozone Therapy Schools. AEPROMO. Madrid, España: Spanish Association of Medical Professionals in Ozone Therapy (AEPROMO); 2010.  Back to cited text no. 12
    
13.
Ozturk O, Tezcan AH, Adali Y, Yıldırım CH, Aksoy O, Yagmurdur H, et al. Effect of ozone and methylprednisolone treatment following crush type sciatic nerve injury. Acta Cir Bras 2016;31:730-5.  Back to cited text no. 13
    
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Rashid U, Rauf F, Hameedullah A, Atif M, Leonardi M. Ozonucleolysis in cervical radiculopathy. Neurol Res Surg 2018;1:1-3.  Back to cited text no. 14
    
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Alexandre A, Corò L, Azuelos A, Buric J, Salgado H, Murga M, et al. Intradiscal injection of oxygen-ozone gas mixture for the treatment of cervical disc herniations. Acta Neurochir Suppl 2005;92:79-82.  Back to cited text no. 15
    
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Xiao Y, Tian JL, Li J, Zhang JS. CT-guided ozone injection for the treatment of cervical disc herniation. Riv Ital Ossigeno Ozonoterapia 2006;5:109-15.  Back to cited text no. 17
    
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Magalhaes FN, Dotta L, Sasse A, Teixera MJ, Fonoff ET. Ozone therapy as a treatment for low back pain secondary to herniated disc: A systematic review and meta-analysis of randomized controlled trials. Pain Physician 2012;15:E115-29.  Back to cited text no. 18
    
19.
Muto M, Ambrosanio G, Guarnieri G, Capobianco E, Piccolo G, Annunziata G, et al. Low back pain and sciatica: Treatment with intradiscal-intraforaminal O (2)-O (3) injection. Our experience. Radiol Med 2008;113:695-706.  Back to cited text no. 19
    
20.
Dall'Olio M, Princiotta C, Cirillo L, Budai C, de Santis F, Bartolini S, et al. Oxygen-ozone therapy for herniated lumbar disc in patients with subacute partial motor weakness due to nerve root compression. Interv Neuroradiol 2014;20:547-54.  Back to cited text no. 20
    
21.
Ezeldin M, Leonardi M, Princiotta C, Dall'olio M, Tharwat M, Zaki ML, et al. Percutaneous ozone nucleolysis for lumbar disc herniation. Neuroradiology 2018;60:1231-41.  Back to cited text no. 21
    
22.
Beyaz SG, Altaş C, Sayhan H. Cardiopulmonary arrest and pneumoencephaly developing after epidural oxygen-ozone mixture therapy. Anesth Essays Res 2018;12:285-7.  Back to cited text no. 22
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23.
Corea F, Amici S, Murgia N, Tambasco N. A case of vertebrobasilar stroke during oxygen-ozone therapy. J Stroke Cerebrovasc Dis 2004;13:259-61.  Back to cited text no. 23
    
24.
İlhan B, Doğan H. Novel complication of ozone therapy: Massive emphysema and pneumomediastinum. Am J Emerg Med 2021;41:190-2.  Back to cited text no. 24
    


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