Injection of chymopapain into intervertebral discs. Preliminary report on 72 patients with symptoms of disc disease

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1 Injection of chymopapain into intervertebral discs Preliminary report on 72 patients with symptoms of disc disease BURTON M. ONOFR10, M.D. Mayo Clinic and Mayo Foundation, Rochester, Minnesota v" The author presents an evaluation of 72 patients given intradiscal chymopapain as the treatment for symptoms related to ruptured intervertebral disc. The rationale, criteria for patient selection, risks, and results are described. The author believes that this early follow-up suggests that chymopapain may have a place in the treatment of symptomatic disc protrusions and extrusions. KEY WORDS 9 ruptured intervertebral disc 9 chymopapain I N 1934, Barr and coworkers 13 developed discectomy for nuclear prolapse associated with sciatica and, except for modifications in technique and the addition of fusion, little more was done in the development of alternatives to the open method until Feffer ~ then reported the results of intradiscal hydrocortisone injections which showed a 46.7% permanent remission rate. Smith, et al., IH4 began their clinical investigations with chymopapain in Since that time, about t0,000 patients with symptoms of ruptured intervertebral disc have been treated with intradiscal chymopapain injections. Chymopapain has been shown to depolymerize mucopolysaccharides, with chondroitin sulfate leaving the disc in jmeasurable quantities? 6 In essence, it destroys the gel effect and severely limits the water-binding capacity of the nucleus pulposus. In the days and weeks after the in- troduction of the enzyme, desiccation of the nucleus occurs, leaving the disc space narrowed and decreasing the volume of prolapsed and extruded fragments. 16 Most complaints of back or leg pain are not clear-cut, and many are further complicated by associated legal or psychiatric problems. No uniformly satisfactory diagnostic test exists to substantiate the choice between conservative and surgical treatment of suspected disc disease. Myelography is a necessary adjunct, but many asymptomatic lumbar myelograpbic deformities apparently due to protruded discs have been noted incidentally in the course of cervical or posterior fossa studies. In our experience, results of discography have only a fair correlation with clinical disc findings, and in fact, normal discograms at any space are a rarity in middle-aged persons. Chymopapain is still considered to be at 384 J. Neurosurg. / Volume 42 / April, 1975

Chymopapain for symptomatic intervertebral disc disease the investigative level because of the inconclusiveness of the results after 11 years of clinical experience.

2 Chymopapain for symptomatic intervertebral disc disease the investigative level because of the inconclusiveness of the results after 11 years of clinical experience. The definition of pain and its cause and measurement are part of the problem. After the diagnosis of a protruded or extruded disc has been established, the problem still exists of determining how long conservative measures should be used before adopting more aggressive surgical measures. In an attempt to resolve some of this dilemma, we are reporting the first 72 cases of chemonucleolysis performed at the Mayo Clinic. The follow-up has only been from 6 to 18 months so that the series is presented as a preliminary experience with chymopapain. Clinical Material and Method Patient Selection Each patient was evaluated by a neurologist. A general examination, appropriate blood studies, and x-ray films of the chest and spinal column were made. In cases of profound progressive motor deficit, myelography and then open surgery were performed as an emergency procedure. If the patient had pain with or without minimal neurological deficit, such as sensory loss and mild motor weakness, a course of 2 weeks of hospital bed rest, muscle relaxants, and physical therapy were the first steps in treatment. Almost all of these patients already had undergone extensive conservative therapy, either on their own or at the direction of a referring physician. If symptoms and signs improved, then the conservative management was continued on an outpatient basis. In cases involving compensation or suspected psychiatric illness, a psychiatric examination was made in addition to the routine Minnesota Multiphasic Personality Inventory (MMPI). If all conservative measures failed and the patient had persistent back and leg pain, Pantopaque myelography of the entire spina[ column was done. We consider this an essential step in preoperative evaluation, since approximately 5% of a series of 514 patients at the Mayo Clinic suffering from typical discogenic symptoms proved to have intraspinal tumors) Prior to 1971, if the myelographic~ defect of a protruded or extruded disc was found, disc removal and possible bone fusion were performed. However, since 1971, once the point of surgical intervention has been reached, we have offered the patient the choice of either an open procedure or chemonucleolysis with chymopapain. There are a few exceptions. We avoid offering chymopapain injections to patients who have had previous laminectomies for disc disease or who have a profound root or cauda equina neurological deficit. No patient with a complete myelographic block was selected for dlscolysis. "From the technical aspect, a few patients have been excluded on the basis of bony anatomy that precluded entering the interspace through the lateral approach; this category includes patients in whom the L-5 transverse processes are large and border on sacralization (Fig. 1). Should the patient choose the chymopapain procedure, a period of at least 2 days is allowed to elapse after myelograp'hy; the occasional severe postmyelography headache may require delaying the procedure further. Method After endotracheal induction of general anesthesia, the patient is placed in the left FIG. 1. Anteroposterior lumbar spinal x-ray film showing lateral masses of L-5 vertebral body in close approximation to iliac wings. L-5 space also is well "submerged" between high-riding iliac crests. Lateral insertion of needle into this L-5 space would be impossible. J. Neurosurg. / Volume 42 / April,

3 lateral decubitus position on a special chemonucleolysis operating table (Fig. 2). After preparation and draping, an 18-gauge needle is inserted into the center of the specific nucleus pulposus identified clinically and myelographically as the cause of the patient's symptoms; the needle is introduced 10 cm to the right of the midline and, with the aid of an x-ray image-intensifier, is directed into the central portion of the disc (Fig. 3). Once anteroposterior and lateral films show the needle to be in optimal position; 1 ml o~f 60% Renografin is injected for discography. Early in the series it was routine practice to perform discography at L-4 and L-5 if the myelographic defect was at one of these levels. We found that both discs were almost always abnormal by discography, and a normal-looking disc was a distinct rarity. Because open surgery would not routinely have been done at two levels, we subsequently have limited needle insertion to those discs that appear abnormal on the myelogram or possibly to an adjacent disc if the space was indeterminate due to a short or posteriorly lying thecal sac. Thus, treatment was as closely as possible parallel to the steps we would have used in an open laminectomy. Once the discogram is accomplished and permanent lateral and anteroposterior x-ray films taken, 1 to 2 ml of chymopapain, 2000 units/ml, are injected into the interspace (previous laboratory and clinical investigations have proved that this dose is safe and has no visible effects on the fibrocartilage or anulus):,6,7,15 The needle is left in place for 5 minutes and then is removed. If the needle cannot be introduced into the interspace by the lateral approach, the procedure is terminated. This fiappened in one patient with a "submerged" lumbosacral space with high-riding iliac crests and large transverse processes at L-5. Since then, we have withheld the procedure from three other patients who had a similar skeletal configuration on the roentgenogram. Reverting to the midline transdural approach for the needle placement into the disc was considered an unwarranted risk since water-soluble iodinated contrast materials as well as chymopapain in high enough concentrations can cause subarachnoid bleeding and neurological deficits. However small this risk may be, it should be avoided. We emphasize that the procedure should B. M. Onofrio FIG. 2. Illustration of patient in left lateral decubitus position on chemonucleolysis operating table. This position makes possible excellent visualization by image-intensification x-ray of any of the lumbar interspaces. FIG. 3. Drawing showing lateral approach for chymopapain injection. The needle is inserted 10 cm to the right of the spinous process and is directed by x-ray control to the central portion of involved disc. This approach avoids piercing the dura. always be done in the operating room with the patient under endotracheal anesthesia. Previous reports have documented severe anaphylaxis occurring in 1% of cases? A secure airway is mandatory for successful management of this complication. 386 J. Neurosurg. / Volume 42 / April, 1975

Chymopapain for symptomatic intervertebral disc disease Results Patients who obtain relief of the discogenic symptoms may do so dramatically during their 5- to 7-day postoperative hospitalization or

4 Chymopapain for symptomatic intervertebral disc disease Results Patients who obtain relief of the discogenic symptoms may do so dramatically during their 5- to 7-day postoperative hospitalization or over a period of 6 to 8 weeks at home. In the absence of a progressive neurological deficit, the treatment is not considered a failure until at leas~ 8 weeks have elapsed; if disabling symptoms persist at that time, an open procedure is done. The first 72 patients have been followed for 6 to 18 months after the chymopapain injection. No patient's condition was made worse and none suffered neurological deficit as the result of chymopapain injections. We thought that the period of 6 to 8 weeks was an adequate trial; we believe patients who improved within that period did so as a result of the chymopapain, since none was confined to bed rest or followed the typical course of an open laminectomy patient, many of whom take 2 to 3 months to convalesce. The 32 patients in the asymptomatic category have totally unrestricted activity, are free of pain, and have returned to their former occupations. The 19 patients considered to be markedly improved have resumed their previous level of activities, except that they occasionally have backache after lifting anything weighing more than 25 kg. The nine moderately improved patients have occasional back and leg symptoms that require the use of aspirin, but are otherwise satisfied with their result and desire no further medical evaluation. Five patients had minimal improvement. Pain decreased sufficiently to allow resumption of gainful employment, but only at sedentary work. Seven patients had no change in the back or leg pain that prompted chemonucleolysis. Five of these have had an open operation. One had an extruded disc in a vertebral foramen. A second patient had a narrow lumbar canal with minimal disc protrusion at three lumbar levels; at laminectomy the compressive components were found to be hypertrophic ligamenta flava and hypertrophied facet joints. In both of these patients, the interspaces into which chymopapain had been injected were devoid of nuclear material. Two other patients had very little nucleus pulposus remaining in the interspace, and the etiology of the backache and leg pain remained obscure. None of the four patients who un- derwent subsequent operation at the Mayo Clinic had any abnormality of the extradural space or dura or any epidural scarring as a result of the previous chymopapain injection, and all had virtually empty interspaces. The fifth patient underwent laminectomy at another institution. The only complications were three cases of aspiration pneumonitis, attributable to intubation in the lateral decubitus position. No patient suffered allergic manifestations secondary to chymopapain injections. Overall, in these 72 cases, 83% of the patients are now gainfully employed at their usual jobs and are satisfied with the results of chymopapain injection, 7% were slightly improved, and 10% remained unchanged. Discussion Preoperative myelography, general anesthesia, and the use of the lateral approach for needle insertion with imageintensifier x-ray control are all mandatory for successful discolysis. We believe that chemonucleolysis is a reasonable alternative to open laminectomy and in no way precludes open intervention later~should it fail to ameliorate the patient's symptoms. Discolysis has the advantages of avoiding surgical disruption of muscle and ligamentous attachments or facet joints and avoiding nerve root manipulation. And according to Parkinson and Shields, 1~ chymopapain has a distinct advantage over other possible enzymes. At present 17% of the patients in this series have failed to get a result satisfactory to the patient and to the physician. Interestingly, of the five patients in whom failure of the chymopapain treatment was followed by laminectomy, only one obtained a satisfactory result from the open operation. Some failures will occur no matter how stringent the operative criteria; relaxation of these criteria only invites a larger failure rate. This series indicates that in well-selected patients one might expect a similar rate of success by either the open or closed technique. Addendum Since this paper was compiled, 170 more patients have undergone chymopapain injections for disc disease without fatality, anaphylaxis, or other complications. The success rate remains the same. J. Neurosurg. / Volume 42 / April,

5 B. M. Onofrio References 1. Barr JS: "Sciatica" caused by intervertebraldisc lesions: a report of forty cases of rupture of the intervertebral disc occurring in the low lumbar spine and causing pressure on the cauda equina. J Bone Joint Surg 19: , Barr JS, Hampton AO, Mixter W J: Pain low in the back and "sciatica" due to lesions of the intervertebral disks. JAMA 109: , Barr JS, Mixter W J: Posterior protrusion of the lumbar intervertebral discs. J Bone Joint Snrg 23: , Eyring E J: The biochemistry and physiology of the intervertebral disk. Clin Orthnp 67:16-28, Feffer HL: Treatment of low-back and sciatic pain by the injection of hydrocortisone into degenerated intervertebral discs. J Bone Joint Surg [Am] 38: , Ford LT: Experimental study of chymopapain in cats. Clin Orthop 67:68-71, Gesler RM: Pharmacologic properties of chymopapain. Ciin Orthop 67:47-51, Love JG, Rivers MH: Spinal cord tumors simulating protruded intervertebral disks. JAMA 179: , Macnab I, McCulloch JA, Weiner DS, et al: Chemonucleolysis. Can J Surg 14: , Parkinson D, Shields C: Treatment of protruded lumbar intervertebral discs with chymopapain (Discase). J Neurosurg 39: , 1973 l l. Smith L: Enzyme dissolution of the nucleus pulposus in humans. JAMA 187: , Smith L, Brown JE: Experiences with enzyme dissolution of the nucleus pulposus. Presented at the 4th Combined Orthopedic Meeting, Vancouver, B.C., June 16, Smith L, Brown JE: Treatment of lumbar intervertebral disc lesions by direct injection of chymopapain. J Bone Joint Surg [Br] 49: , Smith L, Garvin P J, Gesler RM, et al: Enzyme dissolution of the nucleus pulposus (1 )letter to the editor). Nature 198: , Stern I J: Biochemistry of chymopapain. Clin Orthop 67:42-46, Stern I J, Cosmas F, Smith L: Urinary polyuronide excretion in man after enzymic dissolution of the chondromucoprotein of the intervertebral disc or surgical stress. Clin Chim Acta 21: , 1968 Address reprint requests to: Burton M. Onofrio, M.D., Mayo Clinic, Rochester, Minnesota J. Neurosurg. / Volume 42 / April, 1975

Lumbar disc prolapse. Done by : Areej Al-Hadidi

Lumbar disc prolapse. Done by : Areej Al-Hadidi Lumbar disc prolapse Done by : Areej Al-Hadidi Anatomy of IVD IVD is composed of two components: 1. anulus fibrosus : it is the outer fibrous layer (fibrocartilage ) **It is comressible &tough 2. nucleus