Symposium on New Skills in Surgery
Chemonucleolysis in the Treatment of Low Back Pain and Sciatica
Henry W. Apfelbach, MD.,* Richard L. Jacobs, MD.,t and Robert D. Ray, MD., PhD.+
Low back pain is one of the most common afflictions of man. Yet, a complete understanding of the mechanisms involved in its etiology still eludes researchers and clinicians. Before the work of Barr and Mixter/ "lumbago" was felt to arise from disorders of the bony and ligamentous structures of the low back. Now, impingement of the herniated intervertebral disc upon a spinal nerve root is accepted as a frequent cause of low back pain and sciatica. However, the results of laminectomy and disc excision in the treatment of low back pain have often been disappointing. Hirsch and Schajawicz3 suggested that low back pain is disco genic and felt that alterations of intradiscal pressure were a cause of low back symptomatology. Surgical discectomy, however, is not the treatment of choice in all cases of discogenic pain. Experiences with chemonucleolysis have challenged many accepted ideas of the etiology and treatment of low back pain. Chemonucleplysis is the injection of an enzyme, chymopapain, into the intervertebral disc space. Lyman Smith, working with Ivan Stern7• 8 and Robert Gesler,6 started an investigative program in 1963 to determine the efficacy of this procedure. Smith and BrownS enlarged upon the original technique of Lindblom4 in diagnostic disc puncture with injection of radiopaque medium to demonstrate various pathologic states of the intervertebral disc. Thus far, chemonucleolysis has been done in over 12,000 patients in the treatment of disco genic pain.
Anatomy and Physiology of the Intervertebral Disc The intervertebral disc is composed of three parts: (1) The cartilaginous (hyaline) endplate of the vertebral body. (2) The annulus fibrosis, a meshwork of very dense collagenous fibers which surrounds and encloses the disc material and is attached to the adjacent vertebral From the Department of Orthopaedic Surgery, The Abraham Lincoln School of Medicine, University of Illinois at the Medical Center, Chicago "Clinical Associate Professor tProfessor t Professor and Chairman
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bodies. A less dense meshwork extends into the central regions of the disc material. (3) The nucleus pulposis, which occupies the center of the disc space and is composed of a thin meshwork of collagenous fibers with mucoprotein gell (with bound water) in the interstices. With aging, there is depolymerization of mucoproteins and decrease in water content in the disc. The effectiveness of the intervertebral disc as a "shock absorber" decreases with age. With lessening in the height of the intervertebral disc space there is a slight decrease in the height of the patient, and some increase in the mobility between vertebral bodies. This stage could be called "degenerative disc disease." Chymopapain Chymopapain is an enzyme isolated from the latex of the papaya. This enzyme, in contact with the disc, causes depolymerization of mucoprotein but has no effect on collagenous structures such as the annulus fibrosis, the ligamentous structures about the vertebral column, or the sheaths of nerve roots. Studies on animals by Gesler with usual therapeutic doses of the enzyme have shown a several hundredfold margin of safety of chymopapain when properly injected into the disc space. This margin of safety is considerably reduced if the enzyme enters the subarachnoid space following improper injection technique. Nonetheless, Gesler has shown that several times the therapeutic dose, when injected into the subarachnoid space, has no significant deleterious effect.
INDICATIONS FOR CHEMONUCLEOLYSIS The indications for chemonucleolysis are the same as those for laminectomy: failure of response to conservative treatment (absolute bedrest for 10 to 14 days), frequent recurrent episodes of sciatica, and inability to pursue gainful employment. With this procedure, instability caused by the surgical approach to the disc is avoided. Further, the patient does not have evidence of an open surgical operation upon his back, which frequently prevents his being hired. Well motivated patients with recurrent sciatica whose life style is seriously affected are sometimes considered candidates for chemonucleolysis but not for laminectomy. A common example is the person with a sedentary occupation whose pleasures are chiefly found in pursuing various forms of athletics. It is our opinion that chemonucleolysis will eventually find its place between conservative treatment and open surgery, the latter to be done when chymopapain injection fails to relieve symptoms. Chemonucleolysis is also the procedure of choice if laminectomy has failed, especially in that group of patients who achieved a satisfactory clinical result which lasted for 1 year or more following their laminectomy. A second laminectomy frequently fails because of inability of the surgeon to penetrate scar and reach the area of pathology. In many of these patients repeat laminectomy also creates additional scarring and further increases instability of the low back. It is our opinion
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that chemonucleolysis offers this group of patients an "everything to gain and nothing to lose" modality of treatment.
Contraindications Contraindications to chemonucleolysis are as follows: (1) Rapidly developing neurologic deficit in which paraplegia is feared. In this instance, immediate laminectomy is indicated. (2) Severe neurologic deficit, e.g., foot drop, evidence of cord bladder (the probability of a completely extruded fragment of nucleus pulposis is high). (3) Spinal stenosis: The incidence of spinal stenosis or narrowing of the spinal canal is greater with increasing age. The syndrome of spinal claudication in the absence of evidence of a Leriche syndrome should suggest spinal stenosis. The patient's sciatica occurs chiefly on walking. Spinal stenosis can be adequately diagnosed only with myelography. (4) Patients who do not fully accept the treatment offered after the procedure is fully explained. Until there is final approval by the Food and Drug Administration, the use of an "experimental" procedure places the surgeon in jeopardy (regarding malpractice). (5) Patients who have been diagnosed as having arachnoiditis; this group of patients almost invariably has had at least one myelogram and one laminectomy. (6) Patients who have previously had injection of chymopapain. The risk of anaphylactic reaction is increased to an unacceptable rate. Preoperative Evaluation In addition to routine admission history, physical examination and routine laboratory studies (including electrocardiography), the following should be considered: (1) Electromyography, performed by a proficient electromyographer, is of value, if fibrillation potentials can be shown. A negative electromyogram, however, does not rule out the presence of a herniated disc. (2) Myelography is done by many surgeons on a routine basis prior to performing chemonucleolysis. However, it is our opinion that myelography is indicated only under the following circumstances: (a) Suspicion of spinal cord tumor. Probably all patients with bilateral sciatica should have myelography. (b) Suspicion of spinal stenosis. (c) Patients with low back pain without sciatica in whom the diagnosis of a herniated intervertebral disc is in question. (d) Psychometric testing through the use of the Minnesota Multiphasic Personality Inventory (MMPI) has been shown by Wiltse9 to be the most reliable predictor of a good clinical response to chemonucleolysis. A poor test score on the hysteria and hypochondriasis portions of the personality inventory correlates with poor clinical response to chemonucleolysis.
TECHNIQUE OF CHEMONUCLEOLYSIS Chemonucleolysis may be done either in the special procedures room of an x-ray department or in the operating room. Most surgeons prefer general anesthesia because the patient is intubated and can be maintained with an open airway in the event of anaphylactic reaction to
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Figure 1. Three approaches to discography (courtesy of Dr. J. E. Brown).
the enzyme. We have no experience using local anesthesia. Surgeons who prefer local anesthesia claim that in the event of anaphylaxis they receive earlier warning from the patient and can institute resuscitative measures sooner. Also, the conscious patient will tell the surgeon if the needle strikes a nerve root as the needle is inserted prior to discography (see "complications"). After being anesthetized, the patient is placed on his left side with elevation of his left flank so that the pelvis "falls away" and tilts to the right. Each surgeon has a somewhat different technique for achieving this position, and special radiolucent operating tables are often used. Following surgical preparation and draping of the patient, discography is done through the lateral approach (Fig. 1). With this approach, it is unnecessary to penetrate the dura. The needle is inserted 8 to 9 cm. lateral to the midline at an angle of 30 to 45 degrees from the horizontal plane. Using an image intensifier, a C-arm type for greatest convenience, the needles are placed "bull's eye" in the center of at least the lowest two disc spaces, and very frequently the lowest three disc spaces (L3-4, L4-5, and L5-S1). One to five cm3 of a water-soluble dye (Conray 60) is injected into each disc space. Roentgenograms are taken in both the anteroposterior and lateral projections and usually reveal one of the following: (1) a normal disc, (2) a degenerative disc, (3) a protruded disc, or (4) an extruded disc (suggested by an epidural leak of the dye up and down the spinal canal). In general, abnormal discs, including those which are "degenerated" are subjected to chymopapain injection. The ideal dose appears to be 3000 units. Most investigators have felt that the degenerated intervertebral disc should be subjected to chymopapain injection because the degenerated disc of today may become the herniated disc of tomorrow. Further, chymopapain injection cannot be repeated at a later date because of anaphylactic reactions.
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Following injection of chymopapain, drapes are immediately removed and the skin of the patient is observed for a pilomotor reaction, the first manifestation of anaphylaxis. In general, anaphylaxis is manifested almost immediately following chymopapain injection by hypotension, tachycardia, and respiratory distress shortly after the appearance of a pilomotor reaction.
POSTOPERATIVE TREATMENT The only thing predictable about chemonucleolysis in the immediate postoperative period is its unpredictability. Many patients awaken completely relieved of back pain and sciatica. More important, however, in prognosticating the effectiveness of a chymopapain injection is the relief of sciatica or at least a change in the character of the patient's sciatica during the next few days. Approximately 60 per cent of patients experience a significant amount of low back pain which frequently does not develop until the second or third postinjection day. This backache usually subsides within 4 to 5 days to a sufficient degree to permit the patient to leave the hospital. Virtually all patients are able to get up to go to the bathroom on the evening of surgery. The level of activity is regulated on an individual basis. Patients are told to avoid sitting as much as possible. They remain recumbent but may take frequent short walks. Patients with severe low back pain should be treated with hydrotherapy. Muscle relaxants and William's exercises appear to be of no value. At the time of discharge, the patient is provided with a set of instructions (Table 1). Table 1.
Hospital Discharge Instructions for Chemonucleolysis Patients
1. For the first few days following discharge, your degree of activity should be much the same as it was during your last day in the hospital. Avoid stooping or bending as much as possible. Do not lift more than 10 lb of weight. 2. If you have a corset, you may wear it if it gives you relief. In general, patients do not require corsets following chemonucleolysis. 3. Do not drive or ride long distances. 4. Avoid awkward or quick motions. You may climb stairs if done slowly. 5. Sleep alone or in a king-sized bed. The mattress should be firm; it need not be "hard." 6. Sleep on your side with your knees drawn up. Do not sleep on your abdomen. If you sleep on your back, use a rolled-up blanket or a pillow under your knees. 7. Do not do any "exercises." After 2 weeks you may swim conservatively in a warm swimming pool-no diving, breast stroke, or crawl. If indicated, an exercise program will be arranged at the time of your 2-month check-up. S. Call the office if you have any questions concerning your medications. 9. For renewal of medications have your pharmacist call the office. 10. Please call for a follow-up appointment 2 to 3 weeks following your hospital discharge.
REMEMBER The recovery rate varies markedly from patient to patient. A slow recovery should not suggest a poor outcome. You may avoid considerable confusion by not comparing your case with others who have undergone chemonucleolysis.
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In addition to the usual analgesics, we have placed our patients on a 4-day course of prednisone. A sufficient number of patients have not as yet been so treated to evaluate the effectiveness of this drug in avoiding post-injection backache. The nature of the post-injection backache suggests a disc space inflammation; this is the rationale for the steroid therapy. The patient's return to work varies greatly and depends not only upon the nature of his occupation, but also upon his degree of postinjection backache. In general, the patient should remain out of work a minimum of 3 weeks from a sedentary occupation and 6 weeks from light labor.
ILLUSTRATIVE CASE HISTORIES The following case histories not only demonstrate some of the advantages of chemonuc1eolysis over laminectomy but they also illustrate some of the problems which may arise.
CASE
1
A "CLASSIC CASE" OF LOW BACK PAIN WITH SICATICA, NEUROLOGIC DEFICIT, ONE LEVEL DISC PATHOLOGY, AND DRAMATIC CLINICAL RESPONSE. E.S., a 44-yearold housewife had low back pain with right-sided sciatica of 2 years' duration. Periods of bed rest were followed by temporary remissions. Her sciatica was accompanied by paresthesias involving the dorsolateral aspect of her right foot. The patient had been an avid skier and tennis player, but during the past 2 years had not been able to participate in these sports. Examination disclosed reversal of the lumbar lordosis without a list. Straight leg raising was positive at 45 degrees on the right. There was absence of the right Achilles reflex. There was hypesthesia along the dorsolateral aspect of the right foot. Roentgenograms revealed slight narrowing of the L-5, S-l intervertebral disc space. Treatment: Preoperatively, a myelogram was not done, Discography was normal at L3-4 and L4-5. There was extravasation of dye into the spinal canal at L5Sl. On awakening from the anesthesia, the patient was completely relieved of all symptoms. The patient was released on the 5th postoperative day, her discharge being delayed by an unexplained severe headache. She returned to skiing and tennis in 10 weeks. Eight months postinjection there are no symptoms. Except for an absent right Achilles reflex, results of examination remain within normal limits.
CASE
2
SCIATICA WITH NEUROLOGIC FINDINGS WITH MULTILEVEL HERNIATED DISCS. J.L., a 53-year-old executive, had low back pain for approximately 6 years, and was treated during this time by one of us CHWA). He had two previous hospitalizations with complete bed rest on each occasion for 10 days. All of his attacks were characterized by right sciatica, the most recent radiating to the lateral aspect of the right calf and accompanied by paresthesias over the dorsum of the right foot.
r I
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Figure 2. Posterior bulge at L2-3 with extravasation at L3-4, L4-5, and L5-Sl. Degenerated discs at all levels.
Examination disclosed extreme guarding of the low back with reversal of the lumbar lordosis and a 10 degree list to the left. There was depression of the right patellar reflex and absence of the right Achilles reflex. There was 1 inch of atrophy of the right midthigh and 11/2 inches of atrophy of the right midcalf. Roentgenograms disclosed mild to moderate narrowing of the L5-S1 intervertebral disc space. Discography revealed a posterior bulge at L2-L3 with extravasation of dye at L3-4, L4-5, and L5-S1 (Fig. 2). Three thousand units of chymopapain were injected at each of the four levels. This patient was relieved of the greater portion of his sciatica following chemonucleolysis with eventual complete relief of his sciatica. There was rather marked paras pinal muscle spasm for approximately 6 weeks after injection. The patient is novy asymptomatic 5 months after injection and findings on examination are within normal limits. There is complete return of the patellar and Achilles reflexes on the right, as well as disappearance of the atrophy of the right thigh and calf.' Comment: Unexpectedly, Case 2 showed findings on discography consistent with herniated discs at four levels. This patient should be considered in light of traditional surgical treatment, namely myelography and laminectomy. The questions which arise are: How many of these levels would be demonstrable on myelography? Which level or levels gave rise to symptoms? At how many levels would surgical exploration have been done? Although this patient's sciatica was relieved immediately following his disc injection, his recovery was slow. In general, multilevel chymopapain injection gives rise to a greater degree of low back pain.
CASE
3
SCIATICA WITHOUT NEUROLOGIC FINDINGS AND TWO NEGATIVE MYELOGRAMS.
B.W., a 21-year-old college student, had low back pain with left sciatica for approximately 6 months. Her sciatica described as radiating to the left calf and not
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accompanied by paresthesias, caused her to leave school. She was previously evaluated by an orthopedist and two neurologists. Two myelograms had been done with equivocal results. The patient had been told that her problems were probably psychosomatic. Examination disclosed mild restriction of back motion. Straight leg raising was painful at 45 degrees on the left. There were no demonstrable signs of motor weakness, muscle atrophy, or deep tendon reflex changes. Discography disclosed extravasation of dye at L3-4 and L4-5 with a posterior bulge at L5-Sl. Each of the three levels was injected with 3000 units of chymopapain. The patient was discharged on the 6th postoperative day, and complained only of mild residual sciatica. Several weeks later she had neither backache nor sciatica One year after chemonucleolysis, she remains asymptomatic with normal findings on physical examination. Comment: This patient represents a frequently seen dilemma in the treatment of sciatica: the patient with sciatica but no neurologic findings and a negative or equivocal myelogram. The degree of functional overlay is always difficult to evaluate, but perhaps this problem will be solved in the future using psychometric evaluation as described by Wiltse and Rocchio (L. L. Wiltse and P. D. Rocchio: Unpublished data). Where there is sciatica, a negative neurologic examination, and a normal myelogram, we occasionally subject the patient to discography with the understanding that if discography is within normal limits, chymopapain injection will not be done (see "Complications").
CASE
4
BACKACHE WITHOUT SCIATICA. G.L., a 59-year-old housewife, had low back pain for approximately 21/2 years. She had been hospitalized on several occasions with only slight relief of her backache. She was not relieved by use of a brace and by performing William's exercises. Examination disclosed reversal of the lumbar lordosis and marked restriction of bending motions of the low back. There was no list. Straight leg raising was equivocal. Her Achilles reflexes were depressed but equal. There was no motor weakness or muscle atrophy. Roentgenograms of the lumbosacral spine were within normal limits. Because of the absence of sciatica, myelography was done and a filling defect at L5-S1 and a questionable defect at L3-4 were found (Fig. 3). On a second hospital admission, the patient underwent discography and chemonucleolysis. Discography disclosed extravasation of dye at L3-4 and L5-S1 with normal discogram at L4-5. Chymopapain injection was done at L3-4 and L5-Sl. Postoperatively, the patient had very little immediate relief of backache, although she felt that the character of the pain had changed. Her low back pain eventually abated completely and she is asymptomatic 6 months after injection. Comment: In our opinion the patient with low back pain without sciatica should be subjected to myelography prior to consideration of chemonucleolysis. Postoperatively, in this group of patients it is difficult to distinguish whether their backache is a continuation of their original pain or represents the backache of chymopapain injection.
CASE
5
SCIATICA IN A "POOR RISK" PATIENT. H.B., a 65-year-old executive had low back pain with left sciatica radiating to the anterolateral aspect of the right knee for 11/2 years. After bed rest for 4 weeks there was no relief of his sciatica. He had two previous myocardial infarctions, and intermittent claudication of mild degree for 3 years.
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Figure 3. Myelography shows filling defect at L5-S1 and questionable defect at L3-4.
+
There was a normal range of back motion. Straight leg raising was positive at 60 degrees on the left. There was depression of the left Achilles reflex. The popliteal, posterior tibial, and dorsalis pedis pulses were absent bilaterally. Skin temperature was normal in both feet. On his initial hospitalization, an electrocardiogram was grossly abnormal. Aortography showed occlusion of both superficial femoral arteries. Roentgenograms showed severe degenerative arthritis at L4-=-5 (Fig. 4). Myelography showed filling defects at L3-4, L4-5, and L5-S1 (Fig. 5). After these diagnostic procedures the patient was discharged and readmitted 2 weeks later. During the second hospitalization, discography and chemonucleolysis were done. Discography showed extravasation of dye at L4-5 with degenerative disc disease at L3-4 and L5-Sl. Three thousand units of chymopapain were injected at each level. The patient was completely relieved of his sciatica. One year after injection, he remains free of sciatica. His intermittent claudication is unchanged. Comment: Laminectomy in this patient would have been extremely hazardous, especially for three levels of myelographic defects. Anaphylaxis in this patient might well have been fatal, but the incidence of anaphylaxis with chemonucleolysis is sufficiently low to warrant the calculated risk of performing it, as opposed to laminectomy. Note that the degree of degenerative arthritis in this patient did not jeopardize the end result.
CASE
6
RECURRENT SCIATICA IN A PREVIOUSLY LAMINECTOMIZED PATIENT. R.A., the 67-year-old wife of a physician, had undergone a laminectomy with excision of a herniated disc at L4-5 21/2 ,Years previously. She remained asymptomatic for 2 years after surgery and then there was a recurrence of left sciatica. Examination of her lower back was within normal limits. Straight leg raising was positive at 60 degrees on the left. There was depression of the right Achilles reflex. There was no motor weakness, muscle atrophy, or sensory deficit.
H. W.
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Figure 4.
APFELBACH, R.
L. JACOBS, AND R. D. RAY
Severe degenerative arthritis of the spine, especially at L4-5.
Figure 5. Myelography showed filling defects at L3-4, L4-5, and L5-S 1.
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Roentgenograms showed mild narrowing at L4-S and marked narrowing of the LS-Sl intervertebral disc space. Discography disclosed extravasation of dye at the L3-4 level and a posterior bulge at the L4-S and LS-Sl levels. Each of the three levels was injected with 3000 units of chymopapain. The patient was immediately relieved of her sciatica and has remained asymptomatic for 4 months. Comment: The simplicity of doing chemonucleolysis in this patient as compared to laminectomy is obvious. Myelography was not done on this patient but probably would have shown a defect at L3-4, necessitating exploration of at least L3-4 and L4-S.
CASE
7
SCIATICA IN A PREVIOUSLY LAMINECTOMIZED PATIENT WITH NO IMPROVEMENT AFTER LAMINECTOMY. J.R., a 26-year-old male, had undergone laminectomy 11 months previously. The surgeon reported having found posterior bulges of the L4-S and LS-Sl intervertebral disc on the left. Discectomy was done unilaterally at these levels. After laminectomy the patient experienced no relief of his sciatica. Examination was within normal limits with the exception of positive straight leg raising at 60 degrees on the left. Discography disclosed extravasation of dye at L4-S and LS-Sl. Chymopapain injection was done at L4-S and LS-Sl. After injection the patient was not relieved of his sciatica. Three months later myelography was repeated and found to be within normalliInits. Comment: Following chemonucleolysis, we were informed that this patient had been under psychiatric care. His problems were mainly those of depression and anxiety stemming from feelings of inadequacy, chiefly vocational. In all probability, this patient had been achieving secondary gain from his low back problem. As compared to case 6, this patient did not have a good response to his original laminectomy. Failure of response to previous laIninectomy generally gives rise to a poor prognosis for chemonucleolysis as a salvage procedure.
CASE
8
SCIATICA WITH SEVERE PROLONGED BACKACHE FOLLOWING CHEMONUCLEOLYSIS V.J., a 46-year-old high school teacher, had low back pain with left sciatica with multiple attacks over a period of IS years. During the initial examination the patient stated that he had left sciatica radiating to the lateral aspect of his left calf for 6 months. He had been hospitalized for 14 days without relief. Examination disclosed reversal of the lumbar lordosis without a list and moderate restriction of bending motions of the spine. There was restriction of straight leg raising to 4S degrees on the left and depression of the left Achilles reflex. There were no sensory changes. There was neither motor weakness nor muscle atrophy. Roentgenograms disclosed mild narrowing of the L4-S intervertebral disc space. Discography disclosed a posterior bulge of the dye at the L4-S level and extravasation of dye at the LS-Sl level (Fig. 6). Chymopapain injection was done at L4-S and LS-Sl. After disc injection the patient was relieved of his sciatica but complained of severe low back pain. His low back pain persisted for 6 months and he continued to exhibit reversal of his lumbar lordosis with marked discomfort on straight leg raising. His initial sciatica remained absent. Eventually, he made a complete asymptomatic recovery. Fifteen months after injection he remains asymptomatic.
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Figure 6.
Posterior bulge at L4-5 and frank herniation at L5-Sl.
Comment: This occasional complication of chemonucleolysis is most distressing. It must be strongly emphasized that much patience is required in dealing with the backache which often follows chemonucleolysis. This patient experienced the most severe postinjection backache we have seen.
CASE
9
TRAUMATIC NEURITIS AFTER CHEMONUCLEOLYSIS. R.G., a 46-year-old housewife, developed left sciatica following an automobile accident 6 months previously. Her sciatica radiated to the left foot and was accompanied by paresthesias. She was hospitalized for 2 weeks without relief. A myelogram was not done. Examination disclosed moderate restriction of bending motions of the spine. Straight leg raising was positive bilaterally. There was depression of the right patellar and Achilles reflexes. There was no sensory deficit. There was no motor weakness or muscle atrophy. Roentgenograms of the lumbosacral spine were within normal limits. Discography revealed extravasation of dye at the LS-Sl level. Chymopapain injection was done at the LS-Sl level and the patient was immediately relieved of her sciatica. Five days after injection she developed severe burning pain in the (contralateral) right leg, radiating to the dorsum of the right foot. This pain, present at rest, was causalgic in nature. Though the patient is now asymptomatic 9 months after injection, her right leg pain persisted for approximately 3 months after chemonucleolysis. Comment: The LS nerve root was undoubtedly traumatized in this patient during the course of discography. Anatomic studies by Wiltse (personal communication) have shown the close proximity of the LS nerve root to the needle in doing discography at th~ LS-Sl intervertebral disc space. Similar trauma to the nerve root may also occur at other levels, but is less likely. After this experience, We discontinued use of muscle relaxants during anesthesia, so that if the nerve root is impaled a muscle twitch will be felt. The needle can then be backed off and reinserted. We now note only transient episodes of causalgia. Interestingly,
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the causalgia type pain noted by these patients usually develops 4 to 5 days after chemonucleolysis, at the approximate time of hospital discharge.
CASE
10
SCIATICA WITH NO RESPONSE TO CHEMONUCLEOLYSIS BECAUSE OF A COMPLETELY EXTRUDED FRAGMENT OF DISC. G.G., a 37-year-old salesman, had right sciatica for 10 months which radiated to the lateral aspect of the right calf and ankle and was accompanied by paresthesias. The patient had previously been hospitalized with strict bed rest for 10 days without relief of his symptoms. Examination disclosed moderate restriction of motion of the spine. Straight leg raising was positive at 30 degrees on the right and 60 degrees on the left. Neurologic examination was within normal limits, as were roentgenograms of the lumbosacral spine. Discography disclosed extravasation of dye at the L4-5 level with normal discograms at L3-4 and L5-S1 (Fig. 7). Postoperatively, this patient's sciatica was initially relieved. He was discharged 4 days after injection. His right sciatica recurred, actually becoming worse than prior to his chymopapain i~ction. He was rehospitalized and treated conservatively for 10 days without relief. A myelogram was done and a large filling defect at L4-5 was seen (Fig. 8). Laminectomy was done and a completely extruded fragment of disc was found within the spinal canal. Comment: A completely extruded fragment of disc has been the most common cause of failure in chemonucleolysis. We do not feel that the routine use of myelography would be of significant help in differentiating this group of patients. We have performed chemonucleolysis on many patients with a complete block shown by myelography and yet the patient has had an excellent clinical response. Interestingly, laminectomy following chemonucleolysis almost invariably shows
Figure 7. Normal disco gram at L3-4 and L5-Sl. Herniation at L4-5.
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Figure 8.
APFELBACH,
R. L.
JACOBS, AND
R. D.
RAY
Filling defect at L4-5.
the disc space to be an "empty house"-the surgery is usually confined to the removal of the completely extruded fragment.
CASE
11
SCIATICA UNRELIEVED BY CHEMONUCLEOLYSIS BECAUSE OF SPINAL STENOSIS.
11.
.~.
B.P., a 45-year-old male hairdresser, developed right lumbar pain with radiation into the right gluteal region approximately 12 years before being seen by us. He had been treated conservatively with bed rest. Pain was now of such degree that he was unable to continue his work as a hairdresser. There was reversal of the lumbar lordosis with a 20 degree list to the right. Straight leg raising was positive at 70 degrees bilaterally. Neurologic findings, as well as roentgenograms of the lumbosacral spine, were within normal limits. Discography disclosed extravasation of dye at L3-4, a posterior bulge at L5Sl, and degenerative disc disease at L4-5 (Fig. r!). Three thousand units of chymopapain were injected at each of the three levels . Postoperatively, the patient was not relieved of his pain. Ten months after disc. injection the patient developed depression of the right patellar reflex. Myelography was done with no evidence of disc protrusion. However, marked spinal stenosis was noted at the L3-4 level (Fig. 10). Laminectomy was done at L3-4 with decompression of the area of spinal stenosis. Exploration of the disc space at this level failed to disclose any disc herniation. The patient was completely relieved of his symptoms following laminectomy. Comment: This patient was one of our early cases. His symptoms were essentially those of low back pain. At the present time, we would probably subject this patient to myelography before considering chemonucleolysis. We do not feel, however, that the problem of spinal stenosis warrants the use of myelography in all patients under consideration for chemonucleolysis. .
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Figure 9. Discography demonstrates herniation at L3-4, bulge at L5-S1, and degenerative disc disease at L4-5.
* Figure 10.
Spinal stenosis at L3-4 level.
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COMPLICATIONS OF CHYMOPAPAIN INJECTION Anaphylaxis The incidence of anaphylaxis in chemonucleolysis is approximately 1 per cent. There has been one death reported in approximately 12,000 cases. We have had four instances of anaphylaxis in 325 chymopapain injections. Our last three reactions have been relatively mild in degree and have probably been attenuated by prophylactic preoperative use of steroids (0.5 gm of Solu-Cortef given intravenously). Anaphylaxis may also occur after the injection of water-soluble dyes for discography, probably occuring in an incidence equal to that in intravenous pyelography. Fortunately, we have not experienced any reaction to Conray-60, which we believe to be the least irritating of the water-soluble dyes. Anaphylaxis following chymopapain injection almost invariably occurs immediately and is characterized by pilomotor reaction, urticaria, severe hypotension, tachycardia, and respiratory stridor. Epinephrine is given immediately but probably should not be given if development of an anoxic myocardium is evident. When anaphylaxis appears, large doses of steroids should be administered. In our initial case, which was severe, a total of 3.5 gm of Solu-Cortef was used. Because of the development of metabolic acidosis, analogous to that seen in cardiac arrest, large doses of sodium bicarbonate should be administered. With maintenance of an adequate airway, anoxia can usually be avoided. Postoperatively, the patient should be maintained on steroids for several days and should be observed for evidence of renal failure. Failure of Relief of Symptoms of Herniation after Chemonucleolysis Virtually all of our failures have been due to the presence of an extruded fragment of disc which was not reached by chymopapain or spinal stenosis (cases 9 and 10). All surgeons have also seen a small group of patients in whom the cause of failure could not be explained. With psychometric testing this group of patients will be reduced in number. As in previously reported statistics, the success rate of chemonucleolysis has been significantly lower in workman's compensation cases. Surgeons should anticipate a higher failure rate in this group of patients. Traumatic Neuritis As shown in case 9, injury to the spinal nerve in the area of the pedicle should be avoided during discography. A light anesthetic, slow entrance of the needle, and backing off if the nerve root is struck should avoid irreversible injury. Morbidity should be reduced to that seen in· well performed brachial plexus nerve blocks. Those surgeons who carry out chemonucleolysis under local anesthesia, as already mentioned, feel that they are able to eliminate this problem even more satisfactorily. Postinjection Backache Although in most. patients this cannot probably be called a complication (as in case 8), backache may be prolonged. Accordingly, we have in-
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troduced a program of steroid therapy for the 4 postoperative days. We feel that we have significantly reduced the incidence of postinjection backache, but unfortunately have not yet subjected this hypothesis to statistical validation.
Disc Space Infection We have not encountered this rare complication.
DISCUSSION In our opinion, chemonucleolysis represents the treatment of choice for patients with herniated intervertebral disc. Except in those uncommon circumstances where contraindications exist, we feel that it represents the intermediate form of treatment between conservative treatment and laminectomy. In the future, laminectomy probably will become a very uncommon operation. In addition to its high success rate, chemonucleolysis does not create additional instability of the low back. The laboring man will not carry a surgical incision scar into pre-employment physical examination. Hospitalization is significantly shortened. There is, in general, significantly less postoperative morbidity. Herniated discs can be treated in the poor risk patient. An entirely new and simpler approach is presented to the "one-time loser" and repeat laminectomy can frequently be obviated.
REFERENCES 1. Barr, J. S., and Mixter, W. J.: Posterior protrusion of the lumbar intervertebral discs. J. Bone Joint Surg., 23:444, 1941. 2. Gesler, R. M.: Pharmacologic properties of chymopapain. Clin Orthop., 67:47,1969. 3. Hirsch, C., and Schajawicz: Acta Orthop. Scand., 22:184,1952. 4. Lindblom, K.: Diagnostic puncture of intervertebral discs in sciatica. Acta Orthop. Scand., 17:231,1948. 5. Smith, L., and Brown, J. E.: Treatment of lumbar intervertebral disc lesions by direct injection of chymopapain. J. Bone Joint Surg., 49B:502, 1967. 6. Smith, L., Garvin, P. J., Gesler, R. M., and Jennings, R. B.: Enzyme dissolution of the nucleus pulposus. Nature, 198:1311,1963. 7. Stern. I. J., Cosmas, F., and Smith, L.: Urinary polyuronide excretion in man after enzymic dissolution of the chondromucoprotein of the intervertebral disc or surgical stress. Clin. Chim. Acta, 21: 181, 1968. 8. Stern, I. J., and Smith, L.: Dissolution by chymopapain in vitro of tissue from normal or prolapsed intervertebral discs. Clin. Orthop., 50:269, 1967. 9. Wiltse, L. L.: Unpublished material presented at the annual meeting of the American Orthopaedic Association, Hot Springs, Virginia, June 26, 1973. Abraham Lincoln School of Medicine University of Illinois at the Medical Center P. O. Box 6998 Chicago, Illinois 60680
Chemonucleolysis in the Treatment of Low Back Pain and Sciatica
Henry W. Apfelbach, MD.,* Richard L. Jacobs, MD.,t and Robert D. Ray, MD., PhD.+
Low back pain is one of the most common afflictions of man. Yet, a complete understanding of the mechanisms involved in its etiology still eludes researchers and clinicians. Before the work of Barr and Mixter/ "lumbago" was felt to arise from disorders of the bony and ligamentous structures of the low back. Now, impingement of the herniated intervertebral disc upon a spinal nerve root is accepted as a frequent cause of low back pain and sciatica. However, the results of laminectomy and disc excision in the treatment of low back pain have often been disappointing. Hirsch and Schajawicz3 suggested that low back pain is disco genic and felt that alterations of intradiscal pressure were a cause of low back symptomatology. Surgical discectomy, however, is not the treatment of choice in all cases of discogenic pain. Experiences with chemonucleolysis have challenged many accepted ideas of the etiology and treatment of low back pain. Chemonucleplysis is the injection of an enzyme, chymopapain, into the intervertebral disc space. Lyman Smith, working with Ivan Stern7• 8 and Robert Gesler,6 started an investigative program in 1963 to determine the efficacy of this procedure. Smith and BrownS enlarged upon the original technique of Lindblom4 in diagnostic disc puncture with injection of radiopaque medium to demonstrate various pathologic states of the intervertebral disc. Thus far, chemonucleolysis has been done in over 12,000 patients in the treatment of disco genic pain.
Anatomy and Physiology of the Intervertebral Disc The intervertebral disc is composed of three parts: (1) The cartilaginous (hyaline) endplate of the vertebral body. (2) The annulus fibrosis, a meshwork of very dense collagenous fibers which surrounds and encloses the disc material and is attached to the adjacent vertebral From the Department of Orthopaedic Surgery, The Abraham Lincoln School of Medicine, University of Illinois at the Medical Center, Chicago "Clinical Associate Professor tProfessor t Professor and Chairman
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bodies. A less dense meshwork extends into the central regions of the disc material. (3) The nucleus pulposis, which occupies the center of the disc space and is composed of a thin meshwork of collagenous fibers with mucoprotein gell (with bound water) in the interstices. With aging, there is depolymerization of mucoproteins and decrease in water content in the disc. The effectiveness of the intervertebral disc as a "shock absorber" decreases with age. With lessening in the height of the intervertebral disc space there is a slight decrease in the height of the patient, and some increase in the mobility between vertebral bodies. This stage could be called "degenerative disc disease." Chymopapain Chymopapain is an enzyme isolated from the latex of the papaya. This enzyme, in contact with the disc, causes depolymerization of mucoprotein but has no effect on collagenous structures such as the annulus fibrosis, the ligamentous structures about the vertebral column, or the sheaths of nerve roots. Studies on animals by Gesler with usual therapeutic doses of the enzyme have shown a several hundredfold margin of safety of chymopapain when properly injected into the disc space. This margin of safety is considerably reduced if the enzyme enters the subarachnoid space following improper injection technique. Nonetheless, Gesler has shown that several times the therapeutic dose, when injected into the subarachnoid space, has no significant deleterious effect.
INDICATIONS FOR CHEMONUCLEOLYSIS The indications for chemonucleolysis are the same as those for laminectomy: failure of response to conservative treatment (absolute bedrest for 10 to 14 days), frequent recurrent episodes of sciatica, and inability to pursue gainful employment. With this procedure, instability caused by the surgical approach to the disc is avoided. Further, the patient does not have evidence of an open surgical operation upon his back, which frequently prevents his being hired. Well motivated patients with recurrent sciatica whose life style is seriously affected are sometimes considered candidates for chemonucleolysis but not for laminectomy. A common example is the person with a sedentary occupation whose pleasures are chiefly found in pursuing various forms of athletics. It is our opinion that chemonucleolysis will eventually find its place between conservative treatment and open surgery, the latter to be done when chymopapain injection fails to relieve symptoms. Chemonucleolysis is also the procedure of choice if laminectomy has failed, especially in that group of patients who achieved a satisfactory clinical result which lasted for 1 year or more following their laminectomy. A second laminectomy frequently fails because of inability of the surgeon to penetrate scar and reach the area of pathology. In many of these patients repeat laminectomy also creates additional scarring and further increases instability of the low back. It is our opinion
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that chemonucleolysis offers this group of patients an "everything to gain and nothing to lose" modality of treatment.
Contraindications Contraindications to chemonucleolysis are as follows: (1) Rapidly developing neurologic deficit in which paraplegia is feared. In this instance, immediate laminectomy is indicated. (2) Severe neurologic deficit, e.g., foot drop, evidence of cord bladder (the probability of a completely extruded fragment of nucleus pulposis is high). (3) Spinal stenosis: The incidence of spinal stenosis or narrowing of the spinal canal is greater with increasing age. The syndrome of spinal claudication in the absence of evidence of a Leriche syndrome should suggest spinal stenosis. The patient's sciatica occurs chiefly on walking. Spinal stenosis can be adequately diagnosed only with myelography. (4) Patients who do not fully accept the treatment offered after the procedure is fully explained. Until there is final approval by the Food and Drug Administration, the use of an "experimental" procedure places the surgeon in jeopardy (regarding malpractice). (5) Patients who have been diagnosed as having arachnoiditis; this group of patients almost invariably has had at least one myelogram and one laminectomy. (6) Patients who have previously had injection of chymopapain. The risk of anaphylactic reaction is increased to an unacceptable rate. Preoperative Evaluation In addition to routine admission history, physical examination and routine laboratory studies (including electrocardiography), the following should be considered: (1) Electromyography, performed by a proficient electromyographer, is of value, if fibrillation potentials can be shown. A negative electromyogram, however, does not rule out the presence of a herniated disc. (2) Myelography is done by many surgeons on a routine basis prior to performing chemonucleolysis. However, it is our opinion that myelography is indicated only under the following circumstances: (a) Suspicion of spinal cord tumor. Probably all patients with bilateral sciatica should have myelography. (b) Suspicion of spinal stenosis. (c) Patients with low back pain without sciatica in whom the diagnosis of a herniated intervertebral disc is in question. (d) Psychometric testing through the use of the Minnesota Multiphasic Personality Inventory (MMPI) has been shown by Wiltse9 to be the most reliable predictor of a good clinical response to chemonucleolysis. A poor test score on the hysteria and hypochondriasis portions of the personality inventory correlates with poor clinical response to chemonucleolysis.
TECHNIQUE OF CHEMONUCLEOLYSIS Chemonucleolysis may be done either in the special procedures room of an x-ray department or in the operating room. Most surgeons prefer general anesthesia because the patient is intubated and can be maintained with an open airway in the event of anaphylactic reaction to
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Figure 1. Three approaches to discography (courtesy of Dr. J. E. Brown).
the enzyme. We have no experience using local anesthesia. Surgeons who prefer local anesthesia claim that in the event of anaphylaxis they receive earlier warning from the patient and can institute resuscitative measures sooner. Also, the conscious patient will tell the surgeon if the needle strikes a nerve root as the needle is inserted prior to discography (see "complications"). After being anesthetized, the patient is placed on his left side with elevation of his left flank so that the pelvis "falls away" and tilts to the right. Each surgeon has a somewhat different technique for achieving this position, and special radiolucent operating tables are often used. Following surgical preparation and draping of the patient, discography is done through the lateral approach (Fig. 1). With this approach, it is unnecessary to penetrate the dura. The needle is inserted 8 to 9 cm. lateral to the midline at an angle of 30 to 45 degrees from the horizontal plane. Using an image intensifier, a C-arm type for greatest convenience, the needles are placed "bull's eye" in the center of at least the lowest two disc spaces, and very frequently the lowest three disc spaces (L3-4, L4-5, and L5-S1). One to five cm3 of a water-soluble dye (Conray 60) is injected into each disc space. Roentgenograms are taken in both the anteroposterior and lateral projections and usually reveal one of the following: (1) a normal disc, (2) a degenerative disc, (3) a protruded disc, or (4) an extruded disc (suggested by an epidural leak of the dye up and down the spinal canal). In general, abnormal discs, including those which are "degenerated" are subjected to chymopapain injection. The ideal dose appears to be 3000 units. Most investigators have felt that the degenerated intervertebral disc should be subjected to chymopapain injection because the degenerated disc of today may become the herniated disc of tomorrow. Further, chymopapain injection cannot be repeated at a later date because of anaphylactic reactions.
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Following injection of chymopapain, drapes are immediately removed and the skin of the patient is observed for a pilomotor reaction, the first manifestation of anaphylaxis. In general, anaphylaxis is manifested almost immediately following chymopapain injection by hypotension, tachycardia, and respiratory distress shortly after the appearance of a pilomotor reaction.
POSTOPERATIVE TREATMENT The only thing predictable about chemonucleolysis in the immediate postoperative period is its unpredictability. Many patients awaken completely relieved of back pain and sciatica. More important, however, in prognosticating the effectiveness of a chymopapain injection is the relief of sciatica or at least a change in the character of the patient's sciatica during the next few days. Approximately 60 per cent of patients experience a significant amount of low back pain which frequently does not develop until the second or third postinjection day. This backache usually subsides within 4 to 5 days to a sufficient degree to permit the patient to leave the hospital. Virtually all patients are able to get up to go to the bathroom on the evening of surgery. The level of activity is regulated on an individual basis. Patients are told to avoid sitting as much as possible. They remain recumbent but may take frequent short walks. Patients with severe low back pain should be treated with hydrotherapy. Muscle relaxants and William's exercises appear to be of no value. At the time of discharge, the patient is provided with a set of instructions (Table 1). Table 1.
Hospital Discharge Instructions for Chemonucleolysis Patients
1. For the first few days following discharge, your degree of activity should be much the same as it was during your last day in the hospital. Avoid stooping or bending as much as possible. Do not lift more than 10 lb of weight. 2. If you have a corset, you may wear it if it gives you relief. In general, patients do not require corsets following chemonucleolysis. 3. Do not drive or ride long distances. 4. Avoid awkward or quick motions. You may climb stairs if done slowly. 5. Sleep alone or in a king-sized bed. The mattress should be firm; it need not be "hard." 6. Sleep on your side with your knees drawn up. Do not sleep on your abdomen. If you sleep on your back, use a rolled-up blanket or a pillow under your knees. 7. Do not do any "exercises." After 2 weeks you may swim conservatively in a warm swimming pool-no diving, breast stroke, or crawl. If indicated, an exercise program will be arranged at the time of your 2-month check-up. S. Call the office if you have any questions concerning your medications. 9. For renewal of medications have your pharmacist call the office. 10. Please call for a follow-up appointment 2 to 3 weeks following your hospital discharge.
REMEMBER The recovery rate varies markedly from patient to patient. A slow recovery should not suggest a poor outcome. You may avoid considerable confusion by not comparing your case with others who have undergone chemonucleolysis.
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In addition to the usual analgesics, we have placed our patients on a 4-day course of prednisone. A sufficient number of patients have not as yet been so treated to evaluate the effectiveness of this drug in avoiding post-injection backache. The nature of the post-injection backache suggests a disc space inflammation; this is the rationale for the steroid therapy. The patient's return to work varies greatly and depends not only upon the nature of his occupation, but also upon his degree of postinjection backache. In general, the patient should remain out of work a minimum of 3 weeks from a sedentary occupation and 6 weeks from light labor.
ILLUSTRATIVE CASE HISTORIES The following case histories not only demonstrate some of the advantages of chemonuc1eolysis over laminectomy but they also illustrate some of the problems which may arise.
CASE
1
A "CLASSIC CASE" OF LOW BACK PAIN WITH SICATICA, NEUROLOGIC DEFICIT, ONE LEVEL DISC PATHOLOGY, AND DRAMATIC CLINICAL RESPONSE. E.S., a 44-yearold housewife had low back pain with right-sided sciatica of 2 years' duration. Periods of bed rest were followed by temporary remissions. Her sciatica was accompanied by paresthesias involving the dorsolateral aspect of her right foot. The patient had been an avid skier and tennis player, but during the past 2 years had not been able to participate in these sports. Examination disclosed reversal of the lumbar lordosis without a list. Straight leg raising was positive at 45 degrees on the right. There was absence of the right Achilles reflex. There was hypesthesia along the dorsolateral aspect of the right foot. Roentgenograms revealed slight narrowing of the L-5, S-l intervertebral disc space. Treatment: Preoperatively, a myelogram was not done, Discography was normal at L3-4 and L4-5. There was extravasation of dye into the spinal canal at L5Sl. On awakening from the anesthesia, the patient was completely relieved of all symptoms. The patient was released on the 5th postoperative day, her discharge being delayed by an unexplained severe headache. She returned to skiing and tennis in 10 weeks. Eight months postinjection there are no symptoms. Except for an absent right Achilles reflex, results of examination remain within normal limits.
CASE
2
SCIATICA WITH NEUROLOGIC FINDINGS WITH MULTILEVEL HERNIATED DISCS. J.L., a 53-year-old executive, had low back pain for approximately 6 years, and was treated during this time by one of us CHWA). He had two previous hospitalizations with complete bed rest on each occasion for 10 days. All of his attacks were characterized by right sciatica, the most recent radiating to the lateral aspect of the right calf and accompanied by paresthesias over the dorsum of the right foot.
r I
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Figure 2. Posterior bulge at L2-3 with extravasation at L3-4, L4-5, and L5-Sl. Degenerated discs at all levels.
Examination disclosed extreme guarding of the low back with reversal of the lumbar lordosis and a 10 degree list to the left. There was depression of the right patellar reflex and absence of the right Achilles reflex. There was 1 inch of atrophy of the right midthigh and 11/2 inches of atrophy of the right midcalf. Roentgenograms disclosed mild to moderate narrowing of the L5-S1 intervertebral disc space. Discography revealed a posterior bulge at L2-L3 with extravasation of dye at L3-4, L4-5, and L5-S1 (Fig. 2). Three thousand units of chymopapain were injected at each of the four levels. This patient was relieved of the greater portion of his sciatica following chemonucleolysis with eventual complete relief of his sciatica. There was rather marked paras pinal muscle spasm for approximately 6 weeks after injection. The patient is novy asymptomatic 5 months after injection and findings on examination are within normal limits. There is complete return of the patellar and Achilles reflexes on the right, as well as disappearance of the atrophy of the right thigh and calf.' Comment: Unexpectedly, Case 2 showed findings on discography consistent with herniated discs at four levels. This patient should be considered in light of traditional surgical treatment, namely myelography and laminectomy. The questions which arise are: How many of these levels would be demonstrable on myelography? Which level or levels gave rise to symptoms? At how many levels would surgical exploration have been done? Although this patient's sciatica was relieved immediately following his disc injection, his recovery was slow. In general, multilevel chymopapain injection gives rise to a greater degree of low back pain.
CASE
3
SCIATICA WITHOUT NEUROLOGIC FINDINGS AND TWO NEGATIVE MYELOGRAMS.
B.W., a 21-year-old college student, had low back pain with left sciatica for approximately 6 months. Her sciatica described as radiating to the left calf and not
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accompanied by paresthesias, caused her to leave school. She was previously evaluated by an orthopedist and two neurologists. Two myelograms had been done with equivocal results. The patient had been told that her problems were probably psychosomatic. Examination disclosed mild restriction of back motion. Straight leg raising was painful at 45 degrees on the left. There were no demonstrable signs of motor weakness, muscle atrophy, or deep tendon reflex changes. Discography disclosed extravasation of dye at L3-4 and L4-5 with a posterior bulge at L5-Sl. Each of the three levels was injected with 3000 units of chymopapain. The patient was discharged on the 6th postoperative day, and complained only of mild residual sciatica. Several weeks later she had neither backache nor sciatica One year after chemonucleolysis, she remains asymptomatic with normal findings on physical examination. Comment: This patient represents a frequently seen dilemma in the treatment of sciatica: the patient with sciatica but no neurologic findings and a negative or equivocal myelogram. The degree of functional overlay is always difficult to evaluate, but perhaps this problem will be solved in the future using psychometric evaluation as described by Wiltse and Rocchio (L. L. Wiltse and P. D. Rocchio: Unpublished data). Where there is sciatica, a negative neurologic examination, and a normal myelogram, we occasionally subject the patient to discography with the understanding that if discography is within normal limits, chymopapain injection will not be done (see "Complications").
CASE
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BACKACHE WITHOUT SCIATICA. G.L., a 59-year-old housewife, had low back pain for approximately 21/2 years. She had been hospitalized on several occasions with only slight relief of her backache. She was not relieved by use of a brace and by performing William's exercises. Examination disclosed reversal of the lumbar lordosis and marked restriction of bending motions of the low back. There was no list. Straight leg raising was equivocal. Her Achilles reflexes were depressed but equal. There was no motor weakness or muscle atrophy. Roentgenograms of the lumbosacral spine were within normal limits. Because of the absence of sciatica, myelography was done and a filling defect at L5-S1 and a questionable defect at L3-4 were found (Fig. 3). On a second hospital admission, the patient underwent discography and chemonucleolysis. Discography disclosed extravasation of dye at L3-4 and L5-S1 with normal discogram at L4-5. Chymopapain injection was done at L3-4 and L5-Sl. Postoperatively, the patient had very little immediate relief of backache, although she felt that the character of the pain had changed. Her low back pain eventually abated completely and she is asymptomatic 6 months after injection. Comment: In our opinion the patient with low back pain without sciatica should be subjected to myelography prior to consideration of chemonucleolysis. Postoperatively, in this group of patients it is difficult to distinguish whether their backache is a continuation of their original pain or represents the backache of chymopapain injection.
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SCIATICA IN A "POOR RISK" PATIENT. H.B., a 65-year-old executive had low back pain with left sciatica radiating to the anterolateral aspect of the right knee for 11/2 years. After bed rest for 4 weeks there was no relief of his sciatica. He had two previous myocardial infarctions, and intermittent claudication of mild degree for 3 years.
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Figure 3. Myelography shows filling defect at L5-S1 and questionable defect at L3-4.
+
There was a normal range of back motion. Straight leg raising was positive at 60 degrees on the left. There was depression of the left Achilles reflex. The popliteal, posterior tibial, and dorsalis pedis pulses were absent bilaterally. Skin temperature was normal in both feet. On his initial hospitalization, an electrocardiogram was grossly abnormal. Aortography showed occlusion of both superficial femoral arteries. Roentgenograms showed severe degenerative arthritis at L4-=-5 (Fig. 4). Myelography showed filling defects at L3-4, L4-5, and L5-S1 (Fig. 5). After these diagnostic procedures the patient was discharged and readmitted 2 weeks later. During the second hospitalization, discography and chemonucleolysis were done. Discography showed extravasation of dye at L4-5 with degenerative disc disease at L3-4 and L5-Sl. Three thousand units of chymopapain were injected at each level. The patient was completely relieved of his sciatica. One year after injection, he remains free of sciatica. His intermittent claudication is unchanged. Comment: Laminectomy in this patient would have been extremely hazardous, especially for three levels of myelographic defects. Anaphylaxis in this patient might well have been fatal, but the incidence of anaphylaxis with chemonucleolysis is sufficiently low to warrant the calculated risk of performing it, as opposed to laminectomy. Note that the degree of degenerative arthritis in this patient did not jeopardize the end result.
CASE
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RECURRENT SCIATICA IN A PREVIOUSLY LAMINECTOMIZED PATIENT. R.A., the 67-year-old wife of a physician, had undergone a laminectomy with excision of a herniated disc at L4-5 21/2 ,Years previously. She remained asymptomatic for 2 years after surgery and then there was a recurrence of left sciatica. Examination of her lower back was within normal limits. Straight leg raising was positive at 60 degrees on the left. There was depression of the right Achilles reflex. There was no motor weakness, muscle atrophy, or sensory deficit.
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Figure 4.
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Severe degenerative arthritis of the spine, especially at L4-5.
Figure 5. Myelography showed filling defects at L3-4, L4-5, and L5-S 1.
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Roentgenograms showed mild narrowing at L4-S and marked narrowing of the LS-Sl intervertebral disc space. Discography disclosed extravasation of dye at the L3-4 level and a posterior bulge at the L4-S and LS-Sl levels. Each of the three levels was injected with 3000 units of chymopapain. The patient was immediately relieved of her sciatica and has remained asymptomatic for 4 months. Comment: The simplicity of doing chemonucleolysis in this patient as compared to laminectomy is obvious. Myelography was not done on this patient but probably would have shown a defect at L3-4, necessitating exploration of at least L3-4 and L4-S.
CASE
7
SCIATICA IN A PREVIOUSLY LAMINECTOMIZED PATIENT WITH NO IMPROVEMENT AFTER LAMINECTOMY. J.R., a 26-year-old male, had undergone laminectomy 11 months previously. The surgeon reported having found posterior bulges of the L4-S and LS-Sl intervertebral disc on the left. Discectomy was done unilaterally at these levels. After laminectomy the patient experienced no relief of his sciatica. Examination was within normal limits with the exception of positive straight leg raising at 60 degrees on the left. Discography disclosed extravasation of dye at L4-S and LS-Sl. Chymopapain injection was done at L4-S and LS-Sl. After injection the patient was not relieved of his sciatica. Three months later myelography was repeated and found to be within normalliInits. Comment: Following chemonucleolysis, we were informed that this patient had been under psychiatric care. His problems were mainly those of depression and anxiety stemming from feelings of inadequacy, chiefly vocational. In all probability, this patient had been achieving secondary gain from his low back problem. As compared to case 6, this patient did not have a good response to his original laminectomy. Failure of response to previous laIninectomy generally gives rise to a poor prognosis for chemonucleolysis as a salvage procedure.
CASE
8
SCIATICA WITH SEVERE PROLONGED BACKACHE FOLLOWING CHEMONUCLEOLYSIS V.J., a 46-year-old high school teacher, had low back pain with left sciatica with multiple attacks over a period of IS years. During the initial examination the patient stated that he had left sciatica radiating to the lateral aspect of his left calf for 6 months. He had been hospitalized for 14 days without relief. Examination disclosed reversal of the lumbar lordosis without a list and moderate restriction of bending motions of the spine. There was restriction of straight leg raising to 4S degrees on the left and depression of the left Achilles reflex. There were no sensory changes. There was neither motor weakness nor muscle atrophy. Roentgenograms disclosed mild narrowing of the L4-S intervertebral disc space. Discography disclosed a posterior bulge of the dye at the L4-S level and extravasation of dye at the LS-Sl level (Fig. 6). Chymopapain injection was done at L4-S and LS-Sl. After disc injection the patient was relieved of his sciatica but complained of severe low back pain. His low back pain persisted for 6 months and he continued to exhibit reversal of his lumbar lordosis with marked discomfort on straight leg raising. His initial sciatica remained absent. Eventually, he made a complete asymptomatic recovery. Fifteen months after injection he remains asymptomatic.
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Figure 6.
Posterior bulge at L4-5 and frank herniation at L5-Sl.
Comment: This occasional complication of chemonucleolysis is most distressing. It must be strongly emphasized that much patience is required in dealing with the backache which often follows chemonucleolysis. This patient experienced the most severe postinjection backache we have seen.
CASE
9
TRAUMATIC NEURITIS AFTER CHEMONUCLEOLYSIS. R.G., a 46-year-old housewife, developed left sciatica following an automobile accident 6 months previously. Her sciatica radiated to the left foot and was accompanied by paresthesias. She was hospitalized for 2 weeks without relief. A myelogram was not done. Examination disclosed moderate restriction of bending motions of the spine. Straight leg raising was positive bilaterally. There was depression of the right patellar and Achilles reflexes. There was no sensory deficit. There was no motor weakness or muscle atrophy. Roentgenograms of the lumbosacral spine were within normal limits. Discography revealed extravasation of dye at the LS-Sl level. Chymopapain injection was done at the LS-Sl level and the patient was immediately relieved of her sciatica. Five days after injection she developed severe burning pain in the (contralateral) right leg, radiating to the dorsum of the right foot. This pain, present at rest, was causalgic in nature. Though the patient is now asymptomatic 9 months after injection, her right leg pain persisted for approximately 3 months after chemonucleolysis. Comment: The LS nerve root was undoubtedly traumatized in this patient during the course of discography. Anatomic studies by Wiltse (personal communication) have shown the close proximity of the LS nerve root to the needle in doing discography at th~ LS-Sl intervertebral disc space. Similar trauma to the nerve root may also occur at other levels, but is less likely. After this experience, We discontinued use of muscle relaxants during anesthesia, so that if the nerve root is impaled a muscle twitch will be felt. The needle can then be backed off and reinserted. We now note only transient episodes of causalgia. Interestingly,
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the causalgia type pain noted by these patients usually develops 4 to 5 days after chemonucleolysis, at the approximate time of hospital discharge.
CASE
10
SCIATICA WITH NO RESPONSE TO CHEMONUCLEOLYSIS BECAUSE OF A COMPLETELY EXTRUDED FRAGMENT OF DISC. G.G., a 37-year-old salesman, had right sciatica for 10 months which radiated to the lateral aspect of the right calf and ankle and was accompanied by paresthesias. The patient had previously been hospitalized with strict bed rest for 10 days without relief of his symptoms. Examination disclosed moderate restriction of motion of the spine. Straight leg raising was positive at 30 degrees on the right and 60 degrees on the left. Neurologic examination was within normal limits, as were roentgenograms of the lumbosacral spine. Discography disclosed extravasation of dye at the L4-5 level with normal discograms at L3-4 and L5-S1 (Fig. 7). Postoperatively, this patient's sciatica was initially relieved. He was discharged 4 days after injection. His right sciatica recurred, actually becoming worse than prior to his chymopapain i~ction. He was rehospitalized and treated conservatively for 10 days without relief. A myelogram was done and a large filling defect at L4-5 was seen (Fig. 8). Laminectomy was done and a completely extruded fragment of disc was found within the spinal canal. Comment: A completely extruded fragment of disc has been the most common cause of failure in chemonucleolysis. We do not feel that the routine use of myelography would be of significant help in differentiating this group of patients. We have performed chemonucleolysis on many patients with a complete block shown by myelography and yet the patient has had an excellent clinical response. Interestingly, laminectomy following chemonucleolysis almost invariably shows
Figure 7. Normal disco gram at L3-4 and L5-Sl. Herniation at L4-5.
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H. W.
Figure 8.
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Filling defect at L4-5.
the disc space to be an "empty house"-the surgery is usually confined to the removal of the completely extruded fragment.
CASE
11
SCIATICA UNRELIEVED BY CHEMONUCLEOLYSIS BECAUSE OF SPINAL STENOSIS.
11.
.~.
B.P., a 45-year-old male hairdresser, developed right lumbar pain with radiation into the right gluteal region approximately 12 years before being seen by us. He had been treated conservatively with bed rest. Pain was now of such degree that he was unable to continue his work as a hairdresser. There was reversal of the lumbar lordosis with a 20 degree list to the right. Straight leg raising was positive at 70 degrees bilaterally. Neurologic findings, as well as roentgenograms of the lumbosacral spine, were within normal limits. Discography disclosed extravasation of dye at L3-4, a posterior bulge at L5Sl, and degenerative disc disease at L4-5 (Fig. r!). Three thousand units of chymopapain were injected at each of the three levels . Postoperatively, the patient was not relieved of his pain. Ten months after disc. injection the patient developed depression of the right patellar reflex. Myelography was done with no evidence of disc protrusion. However, marked spinal stenosis was noted at the L3-4 level (Fig. 10). Laminectomy was done at L3-4 with decompression of the area of spinal stenosis. Exploration of the disc space at this level failed to disclose any disc herniation. The patient was completely relieved of his symptoms following laminectomy. Comment: This patient was one of our early cases. His symptoms were essentially those of low back pain. At the present time, we would probably subject this patient to myelography before considering chemonucleolysis. We do not feel, however, that the problem of spinal stenosis warrants the use of myelography in all patients under consideration for chemonucleolysis. .
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Figure 9. Discography demonstrates herniation at L3-4, bulge at L5-S1, and degenerative disc disease at L4-5.
* Figure 10.
Spinal stenosis at L3-4 level.
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RAY
COMPLICATIONS OF CHYMOPAPAIN INJECTION Anaphylaxis The incidence of anaphylaxis in chemonucleolysis is approximately 1 per cent. There has been one death reported in approximately 12,000 cases. We have had four instances of anaphylaxis in 325 chymopapain injections. Our last three reactions have been relatively mild in degree and have probably been attenuated by prophylactic preoperative use of steroids (0.5 gm of Solu-Cortef given intravenously). Anaphylaxis may also occur after the injection of water-soluble dyes for discography, probably occuring in an incidence equal to that in intravenous pyelography. Fortunately, we have not experienced any reaction to Conray-60, which we believe to be the least irritating of the water-soluble dyes. Anaphylaxis following chymopapain injection almost invariably occurs immediately and is characterized by pilomotor reaction, urticaria, severe hypotension, tachycardia, and respiratory stridor. Epinephrine is given immediately but probably should not be given if development of an anoxic myocardium is evident. When anaphylaxis appears, large doses of steroids should be administered. In our initial case, which was severe, a total of 3.5 gm of Solu-Cortef was used. Because of the development of metabolic acidosis, analogous to that seen in cardiac arrest, large doses of sodium bicarbonate should be administered. With maintenance of an adequate airway, anoxia can usually be avoided. Postoperatively, the patient should be maintained on steroids for several days and should be observed for evidence of renal failure. Failure of Relief of Symptoms of Herniation after Chemonucleolysis Virtually all of our failures have been due to the presence of an extruded fragment of disc which was not reached by chymopapain or spinal stenosis (cases 9 and 10). All surgeons have also seen a small group of patients in whom the cause of failure could not be explained. With psychometric testing this group of patients will be reduced in number. As in previously reported statistics, the success rate of chemonucleolysis has been significantly lower in workman's compensation cases. Surgeons should anticipate a higher failure rate in this group of patients. Traumatic Neuritis As shown in case 9, injury to the spinal nerve in the area of the pedicle should be avoided during discography. A light anesthetic, slow entrance of the needle, and backing off if the nerve root is struck should avoid irreversible injury. Morbidity should be reduced to that seen in· well performed brachial plexus nerve blocks. Those surgeons who carry out chemonucleolysis under local anesthesia, as already mentioned, feel that they are able to eliminate this problem even more satisfactorily. Postinjection Backache Although in most. patients this cannot probably be called a complication (as in case 8), backache may be prolonged. Accordingly, we have in-
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troduced a program of steroid therapy for the 4 postoperative days. We feel that we have significantly reduced the incidence of postinjection backache, but unfortunately have not yet subjected this hypothesis to statistical validation.
Disc Space Infection We have not encountered this rare complication.
DISCUSSION In our opinion, chemonucleolysis represents the treatment of choice for patients with herniated intervertebral disc. Except in those uncommon circumstances where contraindications exist, we feel that it represents the intermediate form of treatment between conservative treatment and laminectomy. In the future, laminectomy probably will become a very uncommon operation. In addition to its high success rate, chemonucleolysis does not create additional instability of the low back. The laboring man will not carry a surgical incision scar into pre-employment physical examination. Hospitalization is significantly shortened. There is, in general, significantly less postoperative morbidity. Herniated discs can be treated in the poor risk patient. An entirely new and simpler approach is presented to the "one-time loser" and repeat laminectomy can frequently be obviated.
REFERENCES 1. Barr, J. S., and Mixter, W. J.: Posterior protrusion of the lumbar intervertebral discs. J. Bone Joint Surg., 23:444, 1941. 2. Gesler, R. M.: Pharmacologic properties of chymopapain. Clin Orthop., 67:47,1969. 3. Hirsch, C., and Schajawicz: Acta Orthop. Scand., 22:184,1952. 4. Lindblom, K.: Diagnostic puncture of intervertebral discs in sciatica. Acta Orthop. Scand., 17:231,1948. 5. Smith, L., and Brown, J. E.: Treatment of lumbar intervertebral disc lesions by direct injection of chymopapain. J. Bone Joint Surg., 49B:502, 1967. 6. Smith, L., Garvin, P. J., Gesler, R. M., and Jennings, R. B.: Enzyme dissolution of the nucleus pulposus. Nature, 198:1311,1963. 7. Stern. I. J., Cosmas, F., and Smith, L.: Urinary polyuronide excretion in man after enzymic dissolution of the chondromucoprotein of the intervertebral disc or surgical stress. Clin. Chim. Acta, 21: 181, 1968. 8. Stern, I. J., and Smith, L.: Dissolution by chymopapain in vitro of tissue from normal or prolapsed intervertebral discs. Clin. Orthop., 50:269, 1967. 9. Wiltse, L. L.: Unpublished material presented at the annual meeting of the American Orthopaedic Association, Hot Springs, Virginia, June 26, 1973. Abraham Lincoln School of Medicine University of Illinois at the Medical Center P. O. Box 6998 Chicago, Illinois 60680
