Acta Neurochir (2005) [Suppl] 92: 79–82 6 Springer-Verlag 2005
Printed in Austria
Intradiscal injection of oxygen-ozone gas mixture for the treatment of cervical disc herniations
A. Alexandre1, L. Coro`1, A. Azuelos1, J. Buric2, H. Salgado3, M. Murga4, F. Marin5, and H. Giocoli6
1EU.N.I. European Neurosurgical Institute, Treviso, Italy 2Clinica Villanova, Firenze, Italy
3Molding Spine Institute, Marbella, Spain
4Neurosurgical Institute, Sevilla University, Sevilla, Spain 5Unidad de Neurocirugia y Cirugia Espinal, Madrid, Spain
6Neurosurgical Clinic Buenos Aires, Department of Neurosurgery, Buenos Aires, Argentina
Summary
For disc herniations the use of open surgical approaches is reduced since new percutaneous methods allowing shrinkage of the disc and improvement of the radicular function are gaining interest. Studies on the spontaneous disappearance of disc fragments have demon- strated autoimmune responses with a chronic inflammatory reaction.
Also radicular pain has been shown to be mostly due to biochemical mechanisms [10]. Researchers in di¤erent fields surprisingly noticed that a brief, calculated, oxidative stress by ozone administration may correct a persistent imbalance due to excessive, chronic oxida- tive injury [4]. Oxygen-ozone gas injection in painful patients has a dramatic e¤ect on clinical symptoms. On these bases the intradiscal injection of oxygen-ozone gas has been conceived [1, 7, 9]. We report the treatment on a series of patients a¤ected by cervical disc pathol- ogy, treated by intradiscal injection of oxygen-ozone gas mixture.
The e¤ects both on pain and on radicular dysfunction are impressive.
The morphological e¤ect of the treatment was also evaluated by pathological examination.
Keywords: Intradiscal injection; disc herniation; oxygen-ozone.
Introduction
In cases of radicular dysfunction due to discal- radicular conflict, the classical surgical treatment by open surgery has shown to entail a number of com- plications or of partial results. Neurosurgeons have always been searching for a method that allows shrinkage of the herniated or protruded disc in order to solve the problem of severe pain and dysfunction found in an enormous amount of patients. Thus a number of percutaneous non-invasive techniques have been conceived with the aim to remove or provoke shrinkage of the discal tissue. The common principle of
these techniques is that of acting directly on the discal structure without access to the spinal canal. This dras- tically reduces the epidural formation of scar tissue, which may lead to compression of the nerve root and adherence to the moving bones. In the last years percutaneous techniques applied in the lumbar area have become increasingly the subject of research with regard to the various aspects of disc pathology and the possible solutions of the problem. Studies on pain originating from this pathology show that it may be due to biochemical mechanisms of acid intoxication of the nerve, which may be somehow independent from the mechanical problem but may result either from an autoimmune reaction, producing a chronic inflam- matory response engendering an acid environment, or a situation of ischemia [10]. These problems may be solved by biochemical treatment, reducing the need for surgical intervention [1–3, 7]. On the other hand, the mechanism of disc shrinkage and elimination of herniated fragments have carefully been studied and the development of an autoimmune response against a
‘‘non-self ’’ material, leading to a chronic inflamma- tory reaction has been demonstrated [6].
The mixture of oxygen and ozone gases has been employed in medicine since the 30s for the treatment of pain and dysfunction in patients a¤ected by throm- botic and ischemic diseases. After decades of expe- rience in these fields, the empirical observations of powerful and long lasting e¤ects of this gas mixture injected in paravertebral muscles for the treatment
of pain and radicular dysfunction due to a discal- radicular conflict have led to detailed studies on the subject. Working in di¤erent fields, researchers sur- prisingly noticed that a brief, calculated, oxidative stress, achieved by ozone administration, may correct a permanent imbalance caused by excessive or chronic oxidative injury. It has evolved that modest, repeated ozone treatment increases the activity of superoxide dismutase, catalase, and glutathione peroxidase, in- ducing a state of oxidative stress adaptation with very important therapeutic implications [4]. The mixture is produced by an apparatus (ozone generator) which activates the molecules of diatomic oxygen in a voltaic
arch. Ultraviolet spectrophotometry allows a precise quantification of ozone percentages in the obtained mixture. Jacobs in 1982 reported [8] the absence of side e¤ects in over five million ozone therapy sessions for di¤erent pathologies. The paravertebral intramuscular treatment produces pain relief in the majority of pa- tients, together with decongestion, reabsorption of oedema and increased mobility. This has triggered the idea of injecting the oxygen-ozone mixture in the in- tervertebral disc and the conjugation foramen in order to obtain a powerful e¤ect directly on the pathologi- cal mechanism [1, 7, 9]. Recently application of these gases has been used also in cervical disc pathology.
Fig. 1(a–c ). Introduction of the needle in the disc through the anterior approach. Corresponds to the classical approach as for open surgery
80 A. Alexandre et al.
Patients and methods
From 1997 to 2003, a total of 252 patients were treated by intra- discal oxygen-ozone (0203) injection for cervical disc disease in the di¤erent centres participating in this study. Mean patient age was 38 years, 47% were males. Each patient underwent clinical and electro- physiological and neuroradiological investigation in order to estab- lish a precise diagnosis. In each case the presence of a disc herniation was demonstrated. In 67 (39.8% of cases) multiple level herniation was observed. Patients a¤ected by cervical spinal canal stenosis, dis- carthrosic processes, osteophytes or concomitant CSN pathologies were not included in the series. Patients enrolled had received phar- macological and physical therapy without remedial of the clinical picture. The perspective of solving the problem reducing drug administration and without conventional surgical treatment was o¤ered to the patients who consented after detailed explanation.
Dexamethasone administration, if pre-existing, was interrupted when starting 0203injection. It was never associated with 0203treat- ment. Non steroid drugs were allowed, if occasionally needed. The treatment consisted of an intradiscal injection of 0203preceded and followed by 5 paravertebral injections.
– paravertebral injection consisted of administration of 20 ml of 0203at 10 micrograms/ml concentration, divided into 2 sites of injection: in the paravertebral muscles bilateraly, in the metha- meric level of the pathology.
– intradiscal injection is performed via the classical anterior cervial approach. Its execution requires operative room equipment, al- lowing safe asepsis and anaesthesiologic tools, a radiological apparatus for direct vision of the spine, and the source of the oxygen-ozone mixture. Two to three ml of gas are injected, at 20 micrograms/ml concentration.
Results
1. Among the 252 patients pain symptomatology was completely abolished in 79.3% (200 patients), ame- lioration was obtained in 9.9% (25 patients) and the result was poor in 10.7% (27 patients).
2. Sensory dysfunction was abolished in 78.1% (197 patients) and improved in 16.6% (42 patients). This makes a total of 94.7%. Dysfunction remained un- changed in 5.1% (13 patients).
3. Various degrees of motor dysfunction were present in 78.9% of our 252 patients, i.e. 199 cases. In the great majority of cases it was the question of a mild strength defect and was particularly evident when compared to the non-a¤ected side. The motor defect had pre-existed with a mean pre-duration time of 14 days. Among the total group of 252 pa- tients we observed complete regression of motor deficit in 61.9% (156 patients), partial in 21.4% (54 patients), and insu‰cient in 13.4% (34 patients).
This means a total of positive results in 83.3% of cases.
4. Multiple level disc pathology was present in 67 patients. The treatment was performed simulta- neously in all pathological discs. The results ob-
tained do not di¤er from those obtained for single level pathology.
5. Patients underwent CT/MRI control 7 months af- ter treatment. In 39.6% (100 cases) we observed a significant reduction in volume of the hernia, but correlation with clinical signs was not statistically significant.
Discussion
Experimental models suggest that material from the nucleus pulposus may act as a chemical or im- munologic irritant to the nerve and that these mecha- nisms may produce inflammatory response [10]. Up to now, studies have hypothesized that injection of such a powerful oxidant such as ozone induces over- expression of antioxidant enzymes, which neutralise excessive reactive oxygen species (ROS) formation [4].
Ozone seems to reactivate immune system response.
Several investigations have demonstrated that modest, repeated ozone treatment increases the activity of su- peroxide dismutase, catalase, and other enzymes for antioxidant defence.
After intradiscal injection, ozone can accelerate the degradation of proteoglycans in the degenerated nucleus pulposus, leading to its reabsorption and de- hydration with the consequent reduction of herniated material responsible for nerve root compression [3, 4].
In our opinion, the most important aspect is the bio- chemical modification of the medium in the extradural space. Studies on pain, which often is disproportion- ate to the morphological evidence of discal-radicular conflict, have demonstrated that it is provoked by the presence of acid metabolites coming from the degen- erative processes inside the disc, and from ischemia of the nerve root and of the ganglion. In the 90s atten- tion was brought to A2 phospholipase. Saal demon- strated that A2 phospholipase is the cause of radicular pain, independent of the immunological response or a direct inflammatory process [10]. A2 phospholipase is responsible for the arachidonic acid liberation, and hence prostaglandines. High levels of A2 phospholi- pase have been demonstrated in herniated discs. Ozone injected in the disc and in the peridural space of the conjugation foramen and along the posterior longi- tudinal ligament acts as a powerful stimulus to the activation of antioxidant defence, favouring the nor- malisation of redox balance with neutralisation of aci- dosis, increased synthesis of ATP, Ca2þ reuptake and resolution of oedema [4, 6, 10]. The complete bio-
Intradiscal injection of oxygen-ozone gas mixture for the treatment of cervical disc herniations 81
chemical mechanism is not yet understood, but there is strong clinical evidence that the e¤ect is dramatic, and long lasting. Benefit is rapidly obtained on pain, and on nerve dysfunction, with progressive reduction of tingling. EMG controls have confirmed the recupera- tion of nerve function. We presume that this is ach- ieved by amelioration of nerve ischemia.
Injections even in cases of extruded cervical disc pa- thology were performed and had good results. This is probably due to the fact that the isolated fragment is separated from normal tissues, has higher tendency to dehydration, and a degeneration process is engendered in the course of time.
Much remains to be done, but the possibility of treating patients by an easy method which is rapidly e¤ective for solving clinical problems is at hand. This treatment is useful in patients who did not respond to physical therapy and conventional pain therapy, as a last step in conservative treatment before taking the decision of open surgery. Most of these patients will not need more surgery anymore, since ozone may act directly on the cause eliminating clinical symptoms.
The target of the doctor must be to solve clinical problems, not to correct a morphological aspect of a radiological image. This technique is simple, has no risks, o¤ers to the patient a solution without the dis- comfort of surgery and the possible risks it entails.
References
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2. Alexandre A, Soattin GB, Fumo G (1997) Intradiscal ozone injection: a new solution for herniated disc problems. Miami Cedars University Course for Neurosurgery, Miami July 27 3. Alexandre A, Fumo G (1998) Discolisi percutanea mediante
0203 nell’ernia discale lombare. In: Ceccherelli F, Ricciardi A (eds). Lombalgie e lombosciatalgie. Criteri di diagnosi e cura.
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Correspondence: Alberto Alexandre M.D., Via S.Nicolo` 5, Tre- viso, Italy. e-mail: alexandre@eunionline.com
82 A. Alexandre et al.: Intradiscal injection of oxygen-ozone gas mixture for the treatment of cervical disc herniations
