- Email: [email protected]
Cervical intradiskal injection of aprotinin. Technical note and preliminary report
Surg Neurol 1984;21:539-42
539
Cervical Intradiskal Injection of Aprotinin Technical Note and Preliminary Report F. L e s o i n , M . D . ,
M. Jomin,
M.D.,
C. V i a u d , M . D . , G . L o z e s , M . D . , J. P. P r u v o , M . D . ,
and
J. C l a r i s s e , M . D . Service de Neurochirurgie B and Service de Neuroradiologie, H6pital Regional, Lille, France
Lesoin F, Jomin M, Viaud C, Lozes G, PruvoJP, Clarisse J. Cervical intradiskal injection of aprotonin. Technical note and preliminary report. Surg Neurol 1984;21:539-42.
Chemonucleolysis is widely used in the treatment of disease of the lumbar intervertebral disk. From a series of 28 patients, the authors report their experience using this technique at the cervical level using aprotinin instead of chymopapain. KEYWORDS: Cervical disk; Instillation; Intradiskal; Aprotinin
A technique using percutaneous lysis of intervertebral disks in the treatment of lumbar disk protrusion was described by Smith [15] as early as 1964. Since then, after a long period of controversy, chemonucleolysis has been used as an elegant method in the treatment of lumbar disk disorders. Recently Lazorthes et al [6] have reported their experience using chymopapain at the cervical level in a series o f 15 patients. O u r surgical experience of myeloradiculopathy due to cervical arthrosis [3,7] had led us to use aprotinin within the disk by percutaneous approach. Materials
thesia or hypoesthesia and two had also a discrete radicular m o t o r deficiency. Five patients had a radicular involvement at two levels (three times in C-5, five times in C-6, and two times in C-7), with objective deficiency in the form of radicular paresthesia and hyperesthesia (Table 2). All patients had an amipaque myelogram (Figure 1). Five patients also had a vertebral spine scan (Figure 2). In 27 cases, these investigations revealed a radicular compression due to a degenerated soft disk. Only one patient had a compression due to a combination ofdiskal and osteophytic factors.
Technique All the patients were treated while under general anesthesia in a supine position. In the first 15 patients, the puncture was made under radiologic control by a direct anterior approach while pushing the esophagus and the trachea to one side manually. In the last 13 patients, an anterolateral approach was used after turning the head 45 °. Aprotinin ( 5 - 1 0 mL) was injected after diskography via a double sheathed needle with a diameter less than 0.5 ram. The patient was not restrained and was discharged after 48 hours.
and Methods
For 12 months, we treated 28 patients with intradiskal percutaneous injection o f aprotinin at the cervical level. T h e series consisted of 15 men and 13 women, whose median age was 38 years (ranging from 23-48). We observed them for at least 3 months after treatment. Clinical presentation was at one level for 23 patients (Table 1). All cases presented with a progressive cervicobrachial neuralgia resistant to conservative treatm e n t and localized to a precise territory: C-6 in 10 cases, C-5 in five cases, and C-7 in eight cases. Fifteen patients had objective sensory deficiency in the form of paresAddress reprint requests to: F. Lesoin, M.D., Service de Neurochirurgie B, Lille, 59037, C.H.U, France.
g~) 1984 by Elsevier Science Publishing Co., Inc.
Results All patients were reviewed after 1 week, 3 weeks, and 3 months. The results were satisfactory in 27 of 28 patients, with disappearance of all radicular symptoms in 20 patients upon waking, within 48 hours in 6 patients, and within a week in two. For 27 of 28 patients, all sensory and motor deficiencies had disappeared within 48 hours to 15 days. O n e of the patients had to be operated upon 6 weeks after intradiskal injection because of persisting symptoms. This patient had a mixed compression due to diskal and bony factors. N o neurological complications, either transient or permanent, were observed. These clinical results have been confirmed by electromyograms done pre- and postopera0090-3019/84/$3.00
540
Surg Neurol 1984;21:539-42
Lesoin et al
Table 1. Clinical Presentation at One Level for 23 Patients Number of cases 23 15
Neurological disorders Cervicobrachial neuralgia Sensory deficiency with or without cervicobrachial neuralgia Discrete radicular motor deficiency without cervicobrachial neuralgia
tively in 10 patients and a control vertebral spine scan in 15 patients (Figure 3). This investigation showed the disappearance of the disk protrusion in each case.
Comment Lumbar nucleolysis has been proved useful despite controversial arguments developed in the United States. It is agreed that when patients are carefully selected, the outcome of good results is approximately 7 0 % [9,15,8]. It appeared attractive to transfer this technique to the cervical level in the treatment of cervical radiculopathy due to disk degeneration, secondary to osmotic modification of the nucleus pulposus [4]. The articular cartilage will then erode and ulcerate. The cartilaginous cushion of the disk being reduced, the bony surfaces of the vertebral bodies are subjected to supplementary stresses that initiate a local osteogenesis. This constitutes the normal defense mechanism and tends to lead to intervertebral fusion. This stage being reached, the majority of patients with cervical arthrosis do not develop neurological symptoms (98%). The rest (2%) will develop myeloradicular symptoms, which until now have been treated by disk removal [ 11]. In lumbar chemonucleolysis, the indication must be reserved for those patients with radicular symptoms that have relapsed or progressed due to a protrusion of the disk. The strictly anterior approach developed initially has been abandoned in favor of the diskography approach described by Massare et al [10] in 1974. This approach has the advantage of inserting the needle in the midline of the nucleus pulposus as well as avoiding the aerodigestive axis. We prefer aprotinin to chymopapain both for safety and its specific effect. Chymopapain is a proteolytic enzyme that is active on mucopolysaccharides of the in-
Table 2. Clinical Presentation at Two Levels for Five Patients Number of cases 5 3
Neurological disorders Cervicobrachial neuralgia Sensory deficiency with or without cervicobrachial neuralgia
F i g u r e 1. Amipaque mye/ography shows a compression due to a degenerated soft disk at C5-6 level.
tervertebral disk. T h e hydrolysis provoked in the nucleus sets free degradation products and water that diffuse into the plasma. This mechanism causes a breakdown of the nucleus and a secondary collapse of the cartilaginous ring [1]. The epidural toxicity is considered to be moderate by many authors [1,15,14] whereas this feature is debatable according to Rydevick et al [13], who have shown a progressive involvement of microvessels in the arachnoid leading to intramedullary hemorrhage. Added to this risk, which only occurs when the therapeutic dosage is exceded by 2 to 4 times, is that of anaphylactic shock. It is thought to be of the order of 0.4% in a random series of 25,000 patients [12]. Chymopapain can only be used once and resuscitation facilities must be at hand. Lazorthes et al [6] insist that the injection should be made with the patient under general anesthesia.
Cervical Intradiskal Injection of Aprotinin
Figure 2. The C T scan shows compression by a degenerated soft disk anterolaterally at C5-6 ~same patient as in Figure 1~. T h e s e multiple risks at the cervical level have led us to prefer aprotinin. Aprotinin (trade name in G e r m a n y was Trasylol) is a chain of 58 amino acids, derived from cattle organs, which was introduced in 1953 for the treatment of acute pancreatitis. It appears to be able to inhibit such enzymes as chymotrypsin, trypsin, kallikrein, plasmin, and plasmin activators. It has a molecular
Figure 3. The control C T scan for the same patient (Figure 1 and 2) shows the disappearance of disk protrusion.
Surg Neurol 1984;21:539-42
541
weight of about 6000. Its use was suggested in 1982 by K r a e m e r and Laturnus [5]. Some authors [ 2 - 4 ] have shown that the intervertebral disk behaves as an osmotic system. T h e product of the osmotic pressure in the space within the disk and the hydrostatic pressure in the space outside the disk corresponds to the product of the osmotic pressure outside the disk and the hydrostatic pressure within the disk. Any imbalance favoring one of the variables in this equation will result in a displacement of liquid or substance. This equilibrium can be modified by mechanical and biochemical phenomena. An increase in the n u m b e r of particles inside the disk will result in an influx of fluid. A decrease in the n u m b e r of particles results in loss of water and dessication. In humans between 3 0 - 5 0 years old, there is an increase of macromolecules in the nucleus pulposus that results in fissures in the annulus. The combination of these two factors will lead to disk protrusion. It is possible to reduce osmotic pressure inside the nucleus by instilling appropriate substances. Aprotinin acts by forming a complex between the alkaline polypeptide and chondroitin sulphate [2]. This leads to a decrease in pressure within the disk because these high particles cannot cross the selective permeable intravertebral surface. On the other hand, animal experiments done by Haberland and Matis and by Spangfort [2,16] have shown that intradural injection extending to nervous tissue directly or indirectly via microvessels has no effects. T h e r e is no neurological or immunologic risk. In a series of 211 patients, Kraemer and Laturnus [5] found it to be effective in 6 8 % of cases using aprotinin injection at the lumbar level. A 2-year observation of these patients showed that 11% eventually required surgical intervention. Cervical intradiskal injection with aprotinin has numerous advantages compared to surgical treatment. It is a percutaneous technique that will eventually be performed under local anesthesia. In our last eight patients, which were not included in this study because of the limited period of observation, the treatment with aprotinin injection was given with the patient under local anesthesia. T h e r e was a total absence of toxicity and of immunologic reaction. These two factors seems to guarantee greater safety for the patient and eventually will allow multiple injections in the same patient. In conclusion, aprotinin intradiskal instillation is a good complementary technique to surgical treatment of myeloradiculopathy due to cervical arthrosis. It should be reserved to disk protrusions that result in a progressive radicular syndrome. It is unrealistic to treat osteophytic lesions by this technique, as shown by our results. The safety of aprotinin due to its particular mechanism of action should supplant the use of chymopapain.
542
Surg N e u r o l 1984;21:539-42
References 1. Garvin PJ,Jennings RB, Smith L. Chymopapain: a pharmacologic and toxicologic evaluation in experimental animals. Clin Orthop Relat Res 1965;42:204-23. 2. Haberland G, Matis P. Trasylol, ein pro teinaseninhibiton bei chirurgischen und internen indikationen. Med Welt 1967;18:1367. 3. Jomin M, Combelles G, Lesoin F, Delandsheer JM. Les mydloradiculopa thies par cervicarthrose. Etude clinque et thdrapeutique. Lille Mddical 1978;23:393-405. 4. Kraemer J. Pressure dependent fluid shifts in the intervertebrai disc. Orthop Clin North Am 1977;8:211-6. 5. KraemerJ, Laturnus H. Lumbar in tradiscal instillation with aprotinin. Spine 1982;7:73. 6. Lazorthes Y, Verdie JC, Boetto S, Lagarrigue J, Bonafe A, Manelfe C, Theron J, Courtheoux P, Adam Y, Derlon JM, Adam H, Houtteville JP. Chdmonucl~olyse discale cervicale (~ propos de 14 cas de hernies discales latdrales). Prdsentation orale 33~ congr~s de Neurochirurgie de langue Franqaise, Marrakesh, May 1983. 7. Lesoin F, Bouasakao N, Cama A, Servato R, Jomin M. Place de la decompression chirurgicale par vole antdrieure dans les my~5loradiculopa thies par cervicarthrose (~t propos de 850 observations). Semaine des H6pitaux 1983, in preparation.
Lesoin et al
8. McCulloch JA. Chemonucleolysis: experience with 2000 cases. Clin Orth Rel Res 1980;146:128-35. 9. Macnab I. Chemonucleolysis. Clin Neurosurg 1973;20:183-92. 10. Massare C, Bard M, Tristant H. Discographie cervicale. R~Sflexions sp~Sculatives au plan de la technique et des indications dans notre exp6rience. J Radiol Electrol 1974;55:395-9. 11. Nurick S. The pathogenesis of the spinal cord disorder associated with cervical spondylosis. Brain 1972;95:87-100. 12. Rajagopalan R, Tindal S, Macnab I. Anaphylactic reactions to chymopapain during general anesthesia: a case report. Anesth Analg 1974;53:191-3. 13. Rydevik B, Branemark PI, Nordborg C. Effects of chymopapain on nerve tissue. Acta Orthop Stand 1977;48:216. 14. Schwetschenau P, Ramirez A, Johnson J, Baraes E, Wiggs C, Martins AN. Double blind evaluation ofintra discal chymopapain for herniated lumbar discs, Early results. J Neurosurg 1976; 45:622-7. 15. Smith L. Enzyme dissolution of the nucleus pulposus in humans. JAMA 1964;187:137-40. 16. Spangfort EV. The lumbar disc herniation. Acta Ortho Scand 1972;42.
539
Cervical Intradiskal Injection of Aprotinin Technical Note and Preliminary Report F. L e s o i n , M . D . ,
M. Jomin,
M.D.,
C. V i a u d , M . D . , G . L o z e s , M . D . , J. P. P r u v o , M . D . ,
and
J. C l a r i s s e , M . D . Service de Neurochirurgie B and Service de Neuroradiologie, H6pital Regional, Lille, France
Lesoin F, Jomin M, Viaud C, Lozes G, PruvoJP, Clarisse J. Cervical intradiskal injection of aprotonin. Technical note and preliminary report. Surg Neurol 1984;21:539-42.
Chemonucleolysis is widely used in the treatment of disease of the lumbar intervertebral disk. From a series of 28 patients, the authors report their experience using this technique at the cervical level using aprotinin instead of chymopapain. KEYWORDS: Cervical disk; Instillation; Intradiskal; Aprotinin
A technique using percutaneous lysis of intervertebral disks in the treatment of lumbar disk protrusion was described by Smith [15] as early as 1964. Since then, after a long period of controversy, chemonucleolysis has been used as an elegant method in the treatment of lumbar disk disorders. Recently Lazorthes et al [6] have reported their experience using chymopapain at the cervical level in a series o f 15 patients. O u r surgical experience of myeloradiculopathy due to cervical arthrosis [3,7] had led us to use aprotinin within the disk by percutaneous approach. Materials
thesia or hypoesthesia and two had also a discrete radicular m o t o r deficiency. Five patients had a radicular involvement at two levels (three times in C-5, five times in C-6, and two times in C-7), with objective deficiency in the form of radicular paresthesia and hyperesthesia (Table 2). All patients had an amipaque myelogram (Figure 1). Five patients also had a vertebral spine scan (Figure 2). In 27 cases, these investigations revealed a radicular compression due to a degenerated soft disk. Only one patient had a compression due to a combination ofdiskal and osteophytic factors.
Technique All the patients were treated while under general anesthesia in a supine position. In the first 15 patients, the puncture was made under radiologic control by a direct anterior approach while pushing the esophagus and the trachea to one side manually. In the last 13 patients, an anterolateral approach was used after turning the head 45 °. Aprotinin ( 5 - 1 0 mL) was injected after diskography via a double sheathed needle with a diameter less than 0.5 ram. The patient was not restrained and was discharged after 48 hours.
and Methods
For 12 months, we treated 28 patients with intradiskal percutaneous injection o f aprotinin at the cervical level. T h e series consisted of 15 men and 13 women, whose median age was 38 years (ranging from 23-48). We observed them for at least 3 months after treatment. Clinical presentation was at one level for 23 patients (Table 1). All cases presented with a progressive cervicobrachial neuralgia resistant to conservative treatm e n t and localized to a precise territory: C-6 in 10 cases, C-5 in five cases, and C-7 in eight cases. Fifteen patients had objective sensory deficiency in the form of paresAddress reprint requests to: F. Lesoin, M.D., Service de Neurochirurgie B, Lille, 59037, C.H.U, France.
g~) 1984 by Elsevier Science Publishing Co., Inc.
Results All patients were reviewed after 1 week, 3 weeks, and 3 months. The results were satisfactory in 27 of 28 patients, with disappearance of all radicular symptoms in 20 patients upon waking, within 48 hours in 6 patients, and within a week in two. For 27 of 28 patients, all sensory and motor deficiencies had disappeared within 48 hours to 15 days. O n e of the patients had to be operated upon 6 weeks after intradiskal injection because of persisting symptoms. This patient had a mixed compression due to diskal and bony factors. N o neurological complications, either transient or permanent, were observed. These clinical results have been confirmed by electromyograms done pre- and postopera0090-3019/84/$3.00
540
Surg Neurol 1984;21:539-42
Lesoin et al
Table 1. Clinical Presentation at One Level for 23 Patients Number of cases 23 15
Neurological disorders Cervicobrachial neuralgia Sensory deficiency with or without cervicobrachial neuralgia Discrete radicular motor deficiency without cervicobrachial neuralgia
tively in 10 patients and a control vertebral spine scan in 15 patients (Figure 3). This investigation showed the disappearance of the disk protrusion in each case.
Comment Lumbar nucleolysis has been proved useful despite controversial arguments developed in the United States. It is agreed that when patients are carefully selected, the outcome of good results is approximately 7 0 % [9,15,8]. It appeared attractive to transfer this technique to the cervical level in the treatment of cervical radiculopathy due to disk degeneration, secondary to osmotic modification of the nucleus pulposus [4]. The articular cartilage will then erode and ulcerate. The cartilaginous cushion of the disk being reduced, the bony surfaces of the vertebral bodies are subjected to supplementary stresses that initiate a local osteogenesis. This constitutes the normal defense mechanism and tends to lead to intervertebral fusion. This stage being reached, the majority of patients with cervical arthrosis do not develop neurological symptoms (98%). The rest (2%) will develop myeloradicular symptoms, which until now have been treated by disk removal [ 11]. In lumbar chemonucleolysis, the indication must be reserved for those patients with radicular symptoms that have relapsed or progressed due to a protrusion of the disk. The strictly anterior approach developed initially has been abandoned in favor of the diskography approach described by Massare et al [10] in 1974. This approach has the advantage of inserting the needle in the midline of the nucleus pulposus as well as avoiding the aerodigestive axis. We prefer aprotinin to chymopapain both for safety and its specific effect. Chymopapain is a proteolytic enzyme that is active on mucopolysaccharides of the in-
Table 2. Clinical Presentation at Two Levels for Five Patients Number of cases 5 3
Neurological disorders Cervicobrachial neuralgia Sensory deficiency with or without cervicobrachial neuralgia
F i g u r e 1. Amipaque mye/ography shows a compression due to a degenerated soft disk at C5-6 level.
tervertebral disk. T h e hydrolysis provoked in the nucleus sets free degradation products and water that diffuse into the plasma. This mechanism causes a breakdown of the nucleus and a secondary collapse of the cartilaginous ring [1]. The epidural toxicity is considered to be moderate by many authors [1,15,14] whereas this feature is debatable according to Rydevick et al [13], who have shown a progressive involvement of microvessels in the arachnoid leading to intramedullary hemorrhage. Added to this risk, which only occurs when the therapeutic dosage is exceded by 2 to 4 times, is that of anaphylactic shock. It is thought to be of the order of 0.4% in a random series of 25,000 patients [12]. Chymopapain can only be used once and resuscitation facilities must be at hand. Lazorthes et al [6] insist that the injection should be made with the patient under general anesthesia.
Cervical Intradiskal Injection of Aprotinin
Figure 2. The C T scan shows compression by a degenerated soft disk anterolaterally at C5-6 ~same patient as in Figure 1~. T h e s e multiple risks at the cervical level have led us to prefer aprotinin. Aprotinin (trade name in G e r m a n y was Trasylol) is a chain of 58 amino acids, derived from cattle organs, which was introduced in 1953 for the treatment of acute pancreatitis. It appears to be able to inhibit such enzymes as chymotrypsin, trypsin, kallikrein, plasmin, and plasmin activators. It has a molecular
Figure 3. The control C T scan for the same patient (Figure 1 and 2) shows the disappearance of disk protrusion.
Surg Neurol 1984;21:539-42
541
weight of about 6000. Its use was suggested in 1982 by K r a e m e r and Laturnus [5]. Some authors [ 2 - 4 ] have shown that the intervertebral disk behaves as an osmotic system. T h e product of the osmotic pressure in the space within the disk and the hydrostatic pressure in the space outside the disk corresponds to the product of the osmotic pressure outside the disk and the hydrostatic pressure within the disk. Any imbalance favoring one of the variables in this equation will result in a displacement of liquid or substance. This equilibrium can be modified by mechanical and biochemical phenomena. An increase in the n u m b e r of particles inside the disk will result in an influx of fluid. A decrease in the n u m b e r of particles results in loss of water and dessication. In humans between 3 0 - 5 0 years old, there is an increase of macromolecules in the nucleus pulposus that results in fissures in the annulus. The combination of these two factors will lead to disk protrusion. It is possible to reduce osmotic pressure inside the nucleus by instilling appropriate substances. Aprotinin acts by forming a complex between the alkaline polypeptide and chondroitin sulphate [2]. This leads to a decrease in pressure within the disk because these high particles cannot cross the selective permeable intravertebral surface. On the other hand, animal experiments done by Haberland and Matis and by Spangfort [2,16] have shown that intradural injection extending to nervous tissue directly or indirectly via microvessels has no effects. T h e r e is no neurological or immunologic risk. In a series of 211 patients, Kraemer and Laturnus [5] found it to be effective in 6 8 % of cases using aprotinin injection at the lumbar level. A 2-year observation of these patients showed that 11% eventually required surgical intervention. Cervical intradiskal injection with aprotinin has numerous advantages compared to surgical treatment. It is a percutaneous technique that will eventually be performed under local anesthesia. In our last eight patients, which were not included in this study because of the limited period of observation, the treatment with aprotinin injection was given with the patient under local anesthesia. T h e r e was a total absence of toxicity and of immunologic reaction. These two factors seems to guarantee greater safety for the patient and eventually will allow multiple injections in the same patient. In conclusion, aprotinin intradiskal instillation is a good complementary technique to surgical treatment of myeloradiculopathy due to cervical arthrosis. It should be reserved to disk protrusions that result in a progressive radicular syndrome. It is unrealistic to treat osteophytic lesions by this technique, as shown by our results. The safety of aprotinin due to its particular mechanism of action should supplant the use of chymopapain.
542
Surg N e u r o l 1984;21:539-42
References 1. Garvin PJ,Jennings RB, Smith L. Chymopapain: a pharmacologic and toxicologic evaluation in experimental animals. Clin Orthop Relat Res 1965;42:204-23. 2. Haberland G, Matis P. Trasylol, ein pro teinaseninhibiton bei chirurgischen und internen indikationen. Med Welt 1967;18:1367. 3. Jomin M, Combelles G, Lesoin F, Delandsheer JM. Les mydloradiculopa thies par cervicarthrose. Etude clinque et thdrapeutique. Lille Mddical 1978;23:393-405. 4. Kraemer J. Pressure dependent fluid shifts in the intervertebrai disc. Orthop Clin North Am 1977;8:211-6. 5. KraemerJ, Laturnus H. Lumbar in tradiscal instillation with aprotinin. Spine 1982;7:73. 6. Lazorthes Y, Verdie JC, Boetto S, Lagarrigue J, Bonafe A, Manelfe C, Theron J, Courtheoux P, Adam Y, Derlon JM, Adam H, Houtteville JP. Chdmonucl~olyse discale cervicale (~ propos de 14 cas de hernies discales latdrales). Prdsentation orale 33~ congr~s de Neurochirurgie de langue Franqaise, Marrakesh, May 1983. 7. Lesoin F, Bouasakao N, Cama A, Servato R, Jomin M. Place de la decompression chirurgicale par vole antdrieure dans les my~5loradiculopa thies par cervicarthrose (~t propos de 850 observations). Semaine des H6pitaux 1983, in preparation.
Lesoin et al
8. McCulloch JA. Chemonucleolysis: experience with 2000 cases. Clin Orth Rel Res 1980;146:128-35. 9. Macnab I. Chemonucleolysis. Clin Neurosurg 1973;20:183-92. 10. Massare C, Bard M, Tristant H. Discographie cervicale. R~Sflexions sp~Sculatives au plan de la technique et des indications dans notre exp6rience. J Radiol Electrol 1974;55:395-9. 11. Nurick S. The pathogenesis of the spinal cord disorder associated with cervical spondylosis. Brain 1972;95:87-100. 12. Rajagopalan R, Tindal S, Macnab I. Anaphylactic reactions to chymopapain during general anesthesia: a case report. Anesth Analg 1974;53:191-3. 13. Rydevik B, Branemark PI, Nordborg C. Effects of chymopapain on nerve tissue. Acta Orthop Stand 1977;48:216. 14. Schwetschenau P, Ramirez A, Johnson J, Baraes E, Wiggs C, Martins AN. Double blind evaluation ofintra discal chymopapain for herniated lumbar discs, Early results. J Neurosurg 1976; 45:622-7. 15. Smith L. Enzyme dissolution of the nucleus pulposus in humans. JAMA 1964;187:137-40. 16. Spangfort EV. The lumbar disc herniation. Acta Ortho Scand 1972;42.