RESULTS OF TREATMENT OF SPINAL TUBERCULOSIS BY

Transcription

1 RESULTS OF TREATMENT OF SPINAL TUBERCULOSIS BY MIDDLE-PATH REGIME S. M. TULI, VARANASI, INDIA From the Department of Orthopaedics, Institute of Medical Sciences, Banaras Hindu University, Varanasi The efficacy of modern drugs in the treatment of tuberculosis of the spine has been evaluated by a personal follow-up for three to ten years. Operation on the vertebral lesion was done only for those patients with or without neural complications who failed to respond favourably to drug therapy and rest. Thus absolute indications for operation were present in only 6 per cent of cases without neural involvement and in 60 per cent of patients with neural deficit. Of the patients who responded to drug therapy alone, only 19 per cent revealed increase of kyphosis by more than 10 degrees. The diseased area showed radiological evidence of osseous replacement in 296 per cent of cases, of fibro-osseous union in 50 per cent and of fibrous replacement in 202 per cent. The overall results of this regime compare favourably with those of radical operation. It is suggested that freatment should in the first place be by modern antitubercular drugs. At present two divergent philosophies ofthe management oftuberculosis ofthe spine are prevalent. A number of surgeons (Wilkinson 1950, 1969 ; Orell ; Fell#{228}nder 1955 ; Kondo and Yamada 1957 ; Hodgson, Stock, Fang and Ong 1960; Bailey, Gabriel, Hodgson and Shin 1972) practise surgical extirpation of every vertebral lesion. Another approach (Konstam and Konstam 1958 ; Kaplan 1959; Konstam and Blesovsky 1962; Stevenson and Manning 1962 ; Friedman 1966) claims impressive results from the treatment of such patients primarily by antitubercular drugs and rest alone. We have termed our policy of treatment the middle-path regime because we do not practice universal surgical extirpation nor do we advocate an absolutely conservative approach (Tuli, Srivastava, Varma and Sinha 1967; Tuli 1969; Tuli and Kumar 1971). We have been treating our patients mostly on nonoperative lines with antituberculous chemotherapy, rest and spinal braces. Hospitalisation has been restricted to the paraplegics who were unable to walk, or to patients who required evacuation of abscesses or d#{233}bridement of vertebral lesions or those who accepted fusion of the spine for an unstable and painful lesion. THE MIDDLE-PATH REGIME The middle-path regime is carried out on the following lines. Rest-Rest on a hard bed or plaster bed is enforced. A plaster bed is necessary only for a minority of patients or children who do not realise the value of rest. In the treatment of cervical and cervico-thoracic lesions, traction was used in the early stages to put the diseased part at rest. Drugs-For an adult, streptomycin one gram by intramuscular injection daily is used for about three months. Sodium para-aminosalicylate 12 grams daily in divided doses is given for eighteen months; and isoniazid 300 milligrams daily in divided doses for about twenty-four months. Supportive therapy includes multivitamins, haematinics if necessary and a high protein diet. Doses are modified according to age. No significant complications of this triple drug regime have been observed. We feel that when the tuberculosis is active the patient is able to tolerate this relatively high dose. More recently we have been using a combination of isoniazid (300 milligrams) and thiacetazone (150 milligrams) in some cases instead of isoniazid and sodium para-aminosalicylate, primarily for economic reasons. When resistance to first line antitubercular drugs is apparent it is necessary to change to newer drugs. Preliminary observations suggest that in the near future sodium paraaminosalicylate may be replaced by one of the newer drugs such as ethambutol or rifampicin. The average daily dose of ethambutol is 25 milligrams per kilogram for the first sixty days, to be followed by I 5 milligrams per kilogram for a total period of about two years. Supervision-Radiographs and erythrocyte sedimentation rates are done and patients are called for check up at three to six months intervals. Kyphosis is measured radiologically (Dickson 1967). Resumption of activity-gradual mobilisation of the patient is encouraged with the help of spinal braces after six to nine months of bed rest, depending upon the progress of healing. A spinal brace is continued for about eighteen months to two years, when it is gradually discarded. Abscesses-Abscesses near the surface are aspirated and one gram of streptomycin in solution is instilled at each aspiration. Open drainage of the abscess is performed if aspiration fails to clear it. Not all radiologically visible Professor S. M. Tuli, MS., PH.D., F.A.M.S.,Head, Department of Orthopaedics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, , India. VOL. 57-B, No. 1, FEBRUARY

2 14 S. M. TULI paravertebral abscesses were drained ; drainage was mcidental when decompression was performed for paraplegia or when d#{233}bridement was performed for active tuberculosis. Prevertebral abscesses in the cervical region have been drained under local or general anaesthesia when complicated by difficulty in swallowing or breathing. Drainage of a paravertebral abscess was considered when its radiological size increased in spite of the treatment. Sinuses-In most cases sinuses healed within six to twelve weeks of the start of the treatment. A small number required longer treatment or excision of the tract with or without d#{233}bridement. Neurological complications-in the patients who began to show progressive recovery of neurological complications on triple drug therapy between three to four weeks and who progressed to complete recovery, surgical decompression was considered unnecessary. Decompression of the cord for neurological complication has been performed for patients who did not show progressive recovery after a fair trial of conservative therapy for a few weeks, for patients who developed neurological complications during conservative treatment, for those who showed deterioration of the neurological state while undergoing treatment with antitubercular drugs and bed rest, and for those with a history of recurrence of neurological complication. In advanced cases with motor, sensory and sphincter involvement or those having severe flexor spasms, as well as in elderly patients, decompression was not delayed unduly. In other words we performed decompression for absolute indications (Tuli 1969). Excision-Excisional surgery is recommended for postenor spinal disease with or without neural involvement because of the danger of development of superficial abscesses or sinuses and secondary infection ofthe meninges. D#{233}bridement-Operative d#{233}bridement is advised for patients who do not show arrest of the activity of spinal lesions after three to six months of chemotherapeutic regime, or for patients with recurrence of the disease. TABLE INDICATIONS FOR OPERATION ON THE VERTEBRAL LESION Decompression for neurological complications which failed to respond to conservative therapy. Posterior spinal lesion. Failure ofresponse after three to six months of non-operative treatment. Doubtful diagnosis. Instability after healing. Recurrence of disease or of neural complication. Fusion-Posterior spinal arthrodesis is recommended for unstable spinal lesions in which the disease otherwise seems to be arrested. A lesion is considered mechanically unstable if in spite of the arrest of the vertebral disease I the patient gets discomfort in the back on doing normal work. Radiologically such lesions may show significant destruction of more than two vertebrae and lack of regeneration of vertebral bodies during the process of healing. The main indications for surgical intervention on vertebral lesions are summarised in Table I. Post-operative management-after decompression or d#{233}bridement or arthrodesis the patients are nursed on a hard bed ; when necessary a plaster-of-paris bed is used for the first two to three weeks. In cases with neural complications the patient is gradually mobilised out of the bed with the help of spinal braces six to nine months after the operation. In the absence of paraplegia, mobilisation with spinal braces is started at three to six months. The spinal brace is gradually discarded about twelve to eighteen months after the operation. OPERATIVE PROCEDURES For decompression and d#{233}bridement, with or without bone grafting, the cervical spine and cervico-thoracic junction have been exposedthrough an anterior approach; the thoracic spine and thoraco-lumbar junction through an antero-lateral approach or rarely through the transpleural approach ; and the lumbar spine and lumbo-sacral junction through an extraperitoneal approach or rarely through a transperitoneal approach. Laminectomy has been used for excision of the diseased bone in posterior spinal disease and in cases of paraplegia caused by extradural granuloma or tuberculoma. Anterior transposition of the cord through the antero-lateral route was performed in two cases with an extreme degree of kyphotic deformity and paraplegia. More recently we have been trying to correct severe kyphotic deformities by halo-pelvic traction. RECRUDESCENCE OF DISEASE Recurrence or relapse of a tuberculous lesion in the spine poses a special problem. Sometimes there may be a reactivation complicated by neurological involvement. Perhaps the commonest cause is a grumbling activity of infection caused by a resistant strain of acid fast bacilli in a patient with relatively poor general resistance. In such a situation a thorough clinical and radiological examination may be helpful in localising the areas of activation. Special investigations such as tomo;:aphy and myelography in cases of neural involvement may be of help in localising the disease. The diseased area is explored and thorough clearance is performed. The patient is treated by appropriate supportive therapy, second line antitubercular drugs in conjunction with isoniazid and a three weeks course of streptomycin after operation. At the time of d#{233}bridement bone grafting may be performed if there is any evidence of instability; decompression of the cord is performed when there is neural involvement. THE JOURNAL OF BONE AND JOINT SURGERY

3 RESULTS OF TREATMENT OF SPINAL TUBERCULOSIS BY MIDDLE-PATH REGIME 15 RESULTS The results presented here are based upon personal observations during the treatment of patients suffering from tuberculosis of the spine during the last ten years. The observations are based upon 900 cases, including 200 cases oftuberculous paraplegia. The number of cases which were available for various follow-up studies are mentioned in the appropriate sections. Pain-Back pain and tenderness were relieved in 96 percent of cases at the end of twelve months treatment. Sinuses-All the sinuses healed within one to seven months with treatment by antitubercular drugs (average 3.4 months). Multiple sinuses healed almost simultaneously. There was no problem of persistent sinus formation even after extensive operation. A small number of sinuses which failed to respond to drugs within three to four months healed after excision of the sinus tracks. between six and twelve months. Second line antitubercular drugs were used in conjunction with operation for these recurring cases. Deep-seated radiological paravertebral abscesses-observations regarding response to non-operative treatment are based upon seventy-two patients who had deep-seated radiological abscess and in whom operation was not done as the first procedure. Sixty-eight per cent of abscess shadows disappeared spontaneously within six to twelve months (Figs. 1 to 4), in 16 per cent the shadow regressed to constant size and in 14 per cent it appeared calcified. In 2 per cent of cases the deep seated paravertebral abscess required drainage because the size of the abscess increased in successive radiographs in spite of treatment or because an abscess in the neck caused difficulty in breathing and swallowing. Our observations compare favourably with those of Konstam and Konstam (1958); Kaplan (1959) ; Konstam and Blesovsky (1962); Stevenson FIG. I FIG. 2 Radiographs of a case of tuberculosis of the thoracic spine at the time of presentation (October 1968). The antero-posterior view shows a paravertebral abscess shadow and the lateral view shows a destructive lesion with marked diminution of the intervertebral space. FIG. 3 FIG. 4 Radiographs of the same case fifteen months after treatment as an out-patient by triple drug therapy and appropriate rest. Note spontaneous absorption of the paravertebral abscess, osseous replacement of the intervertebral space, healing by bone block formation and no appreciable increase in kyphosis. Sinus ramification is always greater than can be appreciated from the appearance of the openings or the quantity ofthe discharge. The sinus tracks lead in various directions and for great distances, so that complete operative excision is difficult and indeed impracticable. With triple drug therapy operation is rarely necessary. Similar observations are reported by Bosworth and Wright (1952); Hald (1 955) ; Kaplan (1 959); Konstam and Blesovsky (1962); Bosworth (1963) and Paus (1964). Palpable (peripheral) cold abscesses-repeated aspiration and instillation of streptomycin was sufficient to heal 85 per cent ofabscesses; 10 per cent healed after operative evacuation. Most of the abscesses were healed within six months. Nearly 5 per cent of abscesses were not fully controlled in spite of operative drainage and continuous treatment. These abscesses were probably caused by resistant strains of mycobacterium. Some of them presented with recurrence after a quiescent period varying and Manning(l962); Konstam (1963); American Thoracic Society (1963) and Friedman (1966). The presence of an abscess does not seem to inhibit the process of healing. On the basis of the results of the present and of other studies, it is suggested that a less aggressive attitude should be adopted towards radiologically demonstrable paravertebral abscesses. Drainage may be considered in cases with neurological complications, in those having difficulty in swallowing and breathing, or in those with abscesses getting bigger in spite of adequate antitubercular therapy. Neurological complications-all the patients were given the treatment outlined. The overall results in 200 patients are summarised in Table 11. Thirty-eight per cent recovered on conservative therapy alone and six patients died three to four weeks after admission and the beginning of treatment. The cause of death in these patients was poor general condition with visceral tuberculous foci, VOL. 57-B, No. I, FEBRUARY 1975

4 16 S. M. TULI tuberculous meningitis, or both. In nine cases drainage of prevertebral abscesses was performed in cervical or cervico-thoracic lesions. In the remaining 1 18 patients who failed to respond to closed treatment or whose disease was too far advanced to permit observation for a long time, the cord was decompressed by operation. Of these, eighty-one (69 per cent) recovered fully, thirteen ( 1 1 per cent) had recovery sufficient to enable them to walk with a moderate degree of support, ten (8 per cent) failed to show appreciable motor recovery though they had improvement in sensation and in sphincter function, and fourteen (12 per cent) died. One death occurred forty hours after operation from hypostatic pneumonia; the other patients died between four and twelve weeks after decompression, the causes of death being tuberculous meningitis, uraemia, ascending urinary tract infection, renal failure and toxaemia associated with bedsores. The results of decompression in our series viewed separately from results in patients who responded to the conservative regime may appear to be poorer than those in many other series in which surgical decompression was performed in all the patients. However, in the present series decompression was performed principally when the neurological signs failed to respond to conservative antituberculous treatment while in the series in which decompression was performed in all patients, operation may have received credit for recoveries which would have occurred anyway on conservative therapy alone. The overall response in our series shows a success rate of 785 per cent, which compares favourably with the results of any other series. In Konstam and Blesovsky s (1962) series twenty-eight of fifty-six patients with paraplegia (50 per cent) got well with antitubercular drugs alone and did not need operation. The other twenty-eight (50 per cent) underwent operation. in twenty-six of these simple operations like drainage of abscesses were done and antero-lateral decompression was done in only two. Twenty-five of these recovered. In Friedman s (1966) series ten (43#{149}4per cent) of twenty-three paraplegics recovered with closed methods of treatment and the remaining thirteen (566 per cent) needed operations. Three ( 1 32 per cent) underwent costotransversectomy and ten (43#{149}3 per cent) antero-lateral decompression. in Roaf, Kirkaldy-Willis and Cathro s (1958) series, too, recovery from paraplegia was seen with conservative treatment. Evidently many patients with Pott s paraplegia recover simply with adequate and prolonged treatment by antitubercular drugs. Operative decompression is indicated in patients who fail to respond to drug therapy (Tuli 1969) or in cases of recurrence. TABLE II OVERALL RESULTS IN 200 CASES OF NEURAL INVOLVEMENT COMPLICATING CARIES OF THE SPINE. Minimum duration of follow-up of six months in those surviving Severity of Vertebral Number of neural Number of level patients involvement patients Number Mode of treatment patients of Result Results Number patients of Cervical I 3 Tetraparesis 10 Tetraplegia 3 Cervico-thoracic I 3 Tetraparesis 3 Tetraplegia 10 Thoracic 1 39 Paraparesis 29 Paraplegia 1 10 Thoraco-lumbar 21 Paraparesis I 1 Paraplegia 10 *Lumbar 10 Paraparesis 7 Paraplegia 3 *Lumbocral 4 Paraparesis 2 Paraplegia 2 Conservative 2 Conservative+traction+? drainage 9 Anterior decompression 2 Conservative 2 Conservative + traction +? drainage 7 Anterior decompression 4 Conservative 46 Decompression 93 Conservative 8 Decompression 13 Conservative 8 Decompression 2 Conservative - Decompression 4 Success 10 Partial success 2 Failure 0 Death 1 Success I 2 Partial success 1 Failure 0 Death 0 Success I 11 Partial success 5 Failure 7 Death 16 Success 18 Partial success 0 Failure 2 Death 1 Success 6 Partial success 2 Failure 0 Death 2 Success 0 Partial success 3 Failure I Death 0 * Cauda equina lesion. Patients who had motor weakness but were able to walk without support were classified as having tetraparesis or paraparesis whereas those unable to walk because of paralysis were included under the heading of tetraplegia or paraplegia. Advanced paralysis was often associated with other complications such as para-anaesthesia, sphincter involvement, or both. THE JOURNAL OF BONE AND JOINT SURGERY

5 RESULTS OF TREATMENT OF SPINAL TUBERCULOSIS BY MIDDLE-PATH REGIME 17 Onset and speed of neural recovery after operation-the first objective evidence of neural recovery was observed twenty-four hours to twelve weeks after decompression. No significant correlation was found between the pattern of motor recovery (for instance, starting distally or proximally), the onset and speed of recovery after decompression, and other clinical factors such as degree and duration of neural involvement. Most of the patients showed the first evidence of objective recovery within three weeks of decompression ; others, however, took longer to recover. Four patients in the present series started showing recovery ten and twelve weeks after decompression, two recovered completely and two had partial recovery. The time taken for nearly complete recovery varied between three and six months. Clinical features which influence the prognosis of neurological recovery are shown in Table 111. TABLE CLINICAL FACTORS INFLUENCING PROGNOSIS IN CORD INVOLVEMENT III relapse of the disease. One child who had a very severe kyphotic deformity reported back with neurological cornplications apparently due to the deformity five years after the first presentation. Two patients reported with recrudescence of the disease between three and five years. FIG. 5 FIG. 6 FIG. 7 Lateral radiographs of a case of tuberculosis of cervical spine (fifth to seventh vertebrae) treated by drugs and appropriate rest. Figure 5-(March 1972) at the time ofpresentation. Figure 6-(September 1972). Figure 7-(September 1973) during follow-up. Note reconstruction of the destroyed vertebral bodies, fibrous healing between the sixth and seventh vertebrae and anterior bone bridge formation between fifth and sixth vertebrae. Better prognosis Relatively prognosis poor Cord involvement Degree.... Partial Complete Duration... Shorter Longer Type.... Early onset Late onset Rate of involvement. Slow Rapid Age..... Younger Older General condition.. Good Poor Plantar response-an extensor plantar response, a sign of pyramidal tract involvement, lasted for a very long time. We had an opportunity to study this response eighteen months after the start of treatment in sixty-five patients who had achieved complete neurological recovery. In thirty-six cases (554 per cent) the response was extensor on one or both sides and in twenty-nine cases (446 per cent) it was flexor or equivocal. Early return of the flexor response was seen in cases of milder neurological involvement. Recurrence or relapse of neurological complications-one hundred patients with neurological involvement who had completely recovered were followed up for periods varying from three to ten years. Two reported with recurrence of paraplegia after three years of complete recovery, one due to an extradural granuloma and one apparently due to severe kyphosis. Of 144 patients without neural complication who had complete healing, twenty-four patients were followed for two years, thirty-nine between two and three years, forty-seven between three and four years and thirty-four for more than four years. One hundred and forty-one of these developed neither neurological complications nor FIG. 8 FIG. 9 Lateral radiographs of a case of tuberculosis of lumbar spine. Figure 8-At the time of presentation. Figure 9-After one year oftreatment, as an out-patient, by antitubercular drugs and appropnate rest. Restoration of the bony texture and osseous replacement of the anterior part of the intervertebral space is obvious. Fate of the intervertebral spaces without operation-of the 200 patients who could be followed up for at least one year twelve at the time of presentation showed intact intervertebral spaces. These had central, anterior or appendiceal type of tubercular lesions. The radiological appearance of the intervertebral space in these cases remained unchanged and intact at the last follow-up. The rest ofthe patients had varying degrees of diminution and destruction of intervertebral spaces. Fifteen per cent had fibrous (Figs. 5 to 7), 52 per cent had mixed (partly fibrous and partly osseous) and 3 1 per cent had osseous (Figs. 8 and 9) replacement of the intervertebral spaces. it was observed that in cases in which the disc was completely destroyed and there was obliteration of the intervertebral spaces there were more chances for the VOL. 57-B, No. 1, FEBRUARY

6 18 S. M. TULI FIG. 10 FIG. 11 FIG. 12 FIG. 13 Lateral radiographs ofa case oftuberculosis of the dorso-lumbar region showing a destructive lesion and diminution of the inter-vertebral space at the time of presentation. Figure I0-(March 1966). Figure 1 I-Note spontaneous healing by antitubercular chemotherapy at tie end of twenty-one months (December 1967). Figure 12-At twenty-nine months. Figure 13-At fifty-eight months. A shift from fibrous replacement of the intervertebral space to fibro-osseous and osseous replacement is obvious with longer follow-up. lesion to heal by bony replacement of this space (Figs. 2, 4 and 10 to 13). It was noted that with longer follow-up there was shift from fibrous replacement towards osseous replacement of the intervertebral space (Figs. 10 to 13 and 14 to 16). Fate of the intervertebral space with operation-eleven per cent of cases had mixed fusion and 89 per cent had bony healing of the vertebral lesion when assessed eighteen months after operation. Radiological healing of vertebral lesion-after control of the infection, the spine in most of the patients in the present series achieved stability without severe deformity. In a large proportion of lesions in which tubercular spondylitis was of the paradiscal or metaphysial variety, a spontaneous interbody bony or mixed fusion with clinical healing took place (Table IV). In a much smaller group clinical healing took place, with fibrous replacement of the space between the involved vertebrae. Regeneration of involved vertebral bodies was observed in many cases under the influence of antitubercular drugs (Figs. 5 to 7). Before the use of chemotherapy, when non-osseous tissue persisted between partially destroyed vertebral bodies, the arrest of the disease proved to be temporary in a large number of patients. The disease often became reactivated to break down what had appeared to be a fibrous ankylosis. Long-term prediction regarding recrudescence of the spinal disease in patients with intact intervertebral space or its fibrous replacement cannot be made from the present study. Further work on this aspect is in progress in our institution. However, in the present study we had an opportunity to observe seventeen lesions FIG. 14 FIG. 15 FIG. 16 Lateral radiographs of a child with tuberculosis of the mid-thoracic spine treated by triple drug therapy, appropriate rest and bracing. Figure 14-(1967) at the age of 2 years. Figure 16-( 1971 ) at the age of 6 years. Note gradual reconstruction of the destroyed vertebrae, gradual change to osseous replacement of the disc space with negligible increase in the angle of kyphosis. THE JOURNAL OF BONE AND JOINT SURGERY

7 RESULTS OF TREATMENT OF SPINAL TUBERCULOSIS BY MIDDLE-PATH REGIME 19 in which the intervertebral space was intact or replaced by fibrous tissue. These were followed for periods varying from fifteen to seventy-two months. All these lesions remained inactive during this period of follow-up. Bony and mixed replacement of the intervertebral space were not synonymous with clinical healing. In two patients who had complete bony fusion the disease was still clinically active; another two had mixed fusion and active disease. Observations regarding radiological healing in our and in other series are shown in Table IV. Konstam and Blesovsky s (1962) series and ours have many features in common and can reasonably be compared. It seems probable that if an intervertebral space is intact at the time of first examination-as happens commonly in the central and anterior types of lesions of the body-the space may remain so throughout the course of treatment and follow-up. On the other hand, in the common paradiscal type of disease 847 per cent of lesions achieve fibro-osseous or osseous replacement of the involved discs after twelve months of triple drug therapy. Course of kyphosis in patients not operated upon-observations were based upon 104 lesions followed up for at least one year. In thirty-two cases the kyphosis increased by more than 5 degrees ; the disease in three of these patients was active at the end of twelve months or more of follow-up. In seventy-two cases the kyphosis increased by 5 degrees or less; the lesion in one of these was active after more than twelve months. Increase of kyphosis by more than 30 degrees was seen in only six patients : four of these were children, and all of them had involvement of more than three vertebral bodies. It seemed that multiple vertebral involvement, active growth and situation of the lesion in the thoracic spine were responsible for excessive increase in kyphosis. Increase of kyphosis was observed in 667 per cent of thoraco-lumbar lesions, 55 per cent of thoracic lesions and 333 per cent of lumbar lesions. One of the patients with severe kyphosis who had a clinically and radiologically healed lesion at the end of the treatment started showing neurological complications after five years of follow-up, apparently because of the severe deformity. Conservative treatment in conjunction with triple drug therapy does not prevent the progress ofkyphosis (Konstam and Blesovsky 1962, Paus 1964, Friedman 1966, Dickson 1967). However, even spines with solid posterior fusion have shown progress in kyphosis during follow-up (Bakalim 1960). Similar observations regarding increase in kyphosis have been reported by other workers in patients treated by direct surgical extirpation of the vertebral lesion. In our study an increase of 10 degrees or more of kyphosis was seen in only 20 per cent of lesions during the period of followup. In the rest of the lesions (80 per cent) the curvature of the spine either remained static or kyphosis increased by less than 10 degrees or decreased. Six lesions in the present series had an increase in kyphosis of more than 30 degrees. In all these the lesion was in the thoracic spine. This is in agreement with Puig Gun s (1947) and Friedman s (1966) observations. Puig Gun (1947) stated that the destruction of a thoracic vertebral body resulted in a posterior displacement of the centre ofmotion, a subluxation at the level ofthe articular facets and increase in weight borne by the anterior part of the body. In the lumbar spine, the large bodies and vertical articular facets are more apt to telescope than to angulate. The cervical spine is prevented from telescoping by the interposition of the transverse processes, and in this part of the spine there was the least deformity. Kyphosis is more common in the thoracic spine and this region is subjected to the greatest degree of angulation. Almost the whole of the deformity takes place during the active phase of spinal disease. Development of kyphotic TABLE IV RADIOLOGICAL HEALING IN VARIOUS SERIES Number of cases Healing Fibro-osseous Osseous (mixed) Fibrous Intact disc Total Radical operation Roafet al. (1959). Hodgson and Stock (1960) Paus (1964).. Wilkinson (1969). Primarily drug therapy (622 per cent) 24 (168 per cent) 22 (154 per cent) 8 (56 per cent) Konstam and Blesovsky (1962) Kaplan (1959).. Friedman (1966).. Stevenson and Manning (1962) Tuli and Kumar (1971) (298 per ceno 52 (50 per cent) (144 per cent) 6 (58 per cent) 207 I Strict comparison is difficult because of varying criteria used by different workers to categorise the patients, and varying duration of follow-up. Many workers have used only the term successful fusion, which has been put under osseous healing in this table. The difference between the total number of patients/lesions and the sum of the corresponding figures under various headings in a particular series is due to the fact that some workers have excluded deaths and failures from their figures (adapted from Tuli and Kumar 1971). VOL. 57-B, No. I, FEBRUARY 1975

8 20 S. M. TULI deformity after the clinical healing of the disease seems to be uncertain. The only way to minimise the increase in kyphosis seems to be recumbency in the early active stage and prolonged protection with suitable braces in the later stages. Radiological kyphosis in patients operated upon-adequate assessment of the progress of kyphotic deformity was possible in fifty-two patients who were followed for periods of from two to six years. Increase in kyphotic deformity by 10 degrees or more was observed in 19 per cent ofcases. In the remaining 81 per cent the deformity either remained static or the increase in angulation was less than 10 degrees. The deformity in the operated cases became stable by about eighteen months in most cases. In one case (a child aged four with a lower thoracic lesion) the kyphosis increased by 25 degrees two years after operation, possibly because the disease remained active. There does not seem to be much difference in the behaviour of kyphosis between patients treated by radical operation (Paus 1964), those treated by conservative methods (Konstam and Blesovsky 1962), and those treated by the middle-path method (Tuli and Kumar 1971). Clinicalhealingincaseswithoutneurologicalcomplications- Ninety-six per cent of such lesions were inactive clinically and radiologically after twelve months of drug therapy. All these patients were able to return to their work. Four per cent of lesions did not show a favourable response to conservative treatment : these were subjected to d#{233}bridement; all ofthem were controlled by this method. Clinical healing of the lesions was judged by local and general signs and symptoms and radiological observations. After clinical healing patients engaged themselves in normal activity according to the criteria of Stevenson and Manning (1962) and had complete working capacity as described by Paus (1964). Women were leading their normal family life and many were able to bear children (Wilkinson 1955; Hodgson and Stock 1960; Yeager 1963; Paus 1964). The results of orthodox treatment obviously were poor in the days when antitubercular drugs were not available. Treatment by antitubercular drugs, either conservatively or in conjunction with radical surgical extirpation, on the whole gives good results (Table VI). We feel that the operation should be reserved for complications of spinal tuberculosis such as failure to respond to conservative treatment within three to six months, paraplegia not controlled by chemotherapy, abscess not resolving after repeated aspirations, and pain and instability. Many other workers have similar feelings (Kaplan 1959; Chofnas, Surrett and Severn 1964). Relapse or recurrence of complication-exact assessment of the incidence of relapse or recurrence of complication is not possible because these problems may occur at any period during the lifetime of a patient. Reactivation or development of complications has been observed even during the era of antitubercular drugs as late as twenty years or more after apparent healing (Martin 1970). One hundred and eighty-one cases of tuberculosis of the spine who had achieved clinical healing by following the middle-path regime were followed up by us for periods varying from three to ten years. Two patients (treated earlier by operation) came with recurrence of paraplegia (one due to extradural granuloma and one due to severe kyphotic deformity) ; one child developed complications apparently from severe kyphotic deformity; two patients developed reactivation of the spinal lesion (one had been treated earlier by operation and one had healed with conservative treatment only) ; one patient treated earlier by surgical d#{233}bridement and bone grafting developed recrudescence of the vertebral lesion and died of generalised miliary tuberculosis probably because of resistant organisms. A high incidence of relapse rate or development of neural or other complications cannot be ruled out as some of such patients might not have TABLE OVERALL RESULTS OF VAtuous REGIMES IN SPINAL CARIES V Neural Mortality Healing recovery Relapse (percentage) (percentage) (percentage) (percentage) Orthodox (pre-antibiotic) ? Conservativewithchemotherapy Radical operation Middle-path without any signs of reactivation. Most of the adult patients were either farmers or daily wage earners and they were doing their work well. The overall incidence of healing (Tables V and VI) with conservative treatment varies in different series from 83 to 968 per cent. The incidence of healing after operation is reported as between 80 and 968 per cent reported to our institution for consultation and treatment. The cause of reactivation of the disease in spite of apparently adequate treatment at the time of initial therapy, appears to be lowered nutritional status ofthe patient or acquisition by the organisms of resistance to drugs. The relapse rates reported by Paus (1964) and Girdlestone (1965) were 1 1 and 12 per cent respectively. Kaplan THE JOURNAL OF BONE AND JOINT SURGERY

9 RESULTS OF TREATMENT OF SPINAL TUBERCULOSIS BY MIDDLE-PATH REGIME 21 TABLE VI COMPARISON OF RESULTS IN DIFFERENT SERIES OF PATIENTS TREATED BY VARIOUS WORKERS BY VARIOUS REGIMES, AFTER INTRODUCTION OF EFFECTIVE CHEMOTHERAPY Authors Mode of treatment Clinical healing (percentage) Neural recovery (percentage) Death (percentage) Relapse (percentage) Kondo and Yamada (1957).. Streptomycin alone (non-operative) 209? Streptomycin with Albee s operation 355? Streptomycin with focal d#{233}bridement 52? Falk (1958)..... Cases treated in with streptomycin alone and spinal arthrodesis in 69 per cent 66? Hodgson and Stock (l960fl. Stock (1962) J_. Surgical treatment by anterior approach ? Konstam and Blesovsky (1962). Antituberculous drugs. Operation onlyforfailureforparaplegia Konstam Antituberculous drugs primarily 86 99?? Masalawala (1963)... Focal d#{233}bridement with bone grafting Riskd and Novoszel (1963).. Costovertebrotomy-spondylodesis (resection of one rib with posterior arthrodesis) Kirkaldy-Willis and Thomas (1965) Surgical treatment by direct approach ? Friedman (1966).... Antituberculous drugs primarily 97? Kohli (1967).... Radical operation with antituberculous drugs ? Arct (1968)..... (patients more than 60 years) Antituberculous drugs alone Antero-lateral decompression with bonegrafting Wilkinson (1969).... Operative d#{233}bridement ( ) 80? 2 20 Operative d#{233}bridementwith chemotherapy ( ) Tuli (1969), Tuli and Kumar (1971) Antituberculous drugs; operation for failure only ? The results are not strictly comparable because there are variations regarding clinical material, criteria for clinical healing and duration of follow-up, during which death, recurrence or relapse are calculated. Only those series are tabulated where comparison was reasonably possible.?=difficult to calculate or not given clearly. (1959) reported a rate of recurrence of 2 per cent in 130 patients. In Konstam and Blesovsky s (1962) series only one of 207 patients had recurrence. The low rate of relapse (Table VI) is probably due to the effectiveness of antitubercular drugs currently available. Yeager (1963) observed that prolonged use of combined antimicrobial therapy has lowered the relapse rate to its lowest point in our history. DISCUSSION Radical operation for tuberculous disease of the spine has been recommended by many workers on the supposition that drugs are unable to gain access to skeletal tuberculous abscesses and necrotic bone (Wilkinson 1950, 1955, 1969; Orell 1951; Kondo and Yamada 1957; Hodgson et al. 1960). Fell#{228}nder, Hiertonn and Wallmark (1952); Katayama, Itami, Oya, Tanaka and Maruno (1954) and Hev#{233}rand Risk#{243}(1960) observed various concentrations of streptomycin in the diseased material from human tuberculous lesions, but the results varied widely because of the many uncontrolled parameters in the human clinical material. It has more recently been shown that radioactive dihydrostreptomycin (Andr#{233}1956; Hanngren and Andr#{233}1964; Lindberg 1967) and radioactive para-aminosalicylic acid (Hanngren 1959) reach skeletal tubercular foci. Barclay, Ebert, LeRoy, Manthei and Roth (1953) and Canetti (1955) reported that radioactive isoniazid diffused freely into all tissues including bone, as well as into abscess cavities and even dried caseous material in sufficient concentration to destroy the bacteria. Further work involving the use of bioassay techniques has shown that the concentration of streptomycin in the experimental tuberculous lesion after a single VOL. 57-B, No. I, FEBRUARY 1975

10 22 S. M. TULI intramuscular injection (equivalent to therapeutic doses) is much higher than that considered sufficient to have an inhibitory effect on human type of mycobacterium tuberculosis (Tuli, Brighton, Morton and Clark 1974). Finally, the clinical response of the spinal disease under chemotherapeutic treatment, with the quality of healing that is more rapid and more consistent than seen before the use of the antitubercular drugs, led many workers (Konstam and Konstam 1958, Konstam and Blesovsky 1962, Konstam 1963, Friedman 1966, Dickson 1967, Tuli et a!. 1967, Tuli 1969, Tuli and Kumar 1971) to infer that the drugs were indeed reaching the site of infection. These drugs are so effective that they have made sanatorium treatment unimportant (Fox 1962, 1964) and have obviated the need for routine operation. Few of the comparisons between the results of operative treatment and those of non-operative treatment are valid, because usually the evidence regarding the results of conservative treatment was obtained before modern antitubercular drugs became available (Bailey et a!. 1972). More objective comparison (Tuli 1973) of recent series treated by antitubercular drugs alone or in conjunction with radical operation on the whole offer evidence of the effectiveness of the drugs. Certainly, if the organism is sensitive to the antitubercular drugs and the drug is administered for sufficient length of time, the infection may well be controlled and most of the lesions will heal. If a lesion does not come under control the cause is not failure of the drugs to reach the lesion in sufficient concentration. The cause lies in other factors such as the nature of the mycobacterium (atypical being generally resistant), the resistance ofthe infecting organism to the drugs and the mechanical nature of the pathological lesion-for instance, the presence of large sequestra. The effects of antituberculous drugs on skeletal tuberculosis were aptly summed up in Girdlestone (1965): In every skeletal lesion, there are areas of bone which are infiltrated with tuberculous disease but which are not necrosed. These will recover under drug treatment. There are also areas of ischaemic and infarcted bone and these will also recover without operation because as the disease subsides, the circulation in the lesion improves. Finally, there are areas of necrosis which are past recovery and which harbour tubercular bacilli. For these operative treatment in addition to drugs is essential. Operation should be limited to such foci.. CONCLUSIONS AND SUMMARY By following the middle-path regime absolute indications for surgical intervention on the vertebral lesion are reduced to 6 per cent of cases without neural complications and to 60 per cent of cases with neural deficit. Ninety-four per cent of cases of tuberculosis of the spine without neurological complications can achieve clinical healing with an adequate course of chemotherapy without surgical intervention on the vertebral lesion. The overall results compare favourably with the published results of radical operation. Of the 181 patients treated by the middle-path regime who could be followed up for three to ten years, three had recurrence and three returned with complication of paraplegia. Of the cases with neurological involvement, 38 per cent recovered completely with drug therapy alone ; operation was performed for the remaining failures. Of the patients who underwent decompression and d#{233}bridement for neural complications, 69 per cent recovered completely. The overall success rate in neural complications treated by the middle-path regime was 785 per cent. Ofall the recovered cases, 2 per cent reported again with recurrence of complications. In the patients treated by drug therapy alone, 19 per cent revealed increase of kyphosis by more than 10 degrees. The diseased area went on to osseous replacement in 296 per cent, fibro-osseous in 50 per cent and fibrous in 202 per cent of cases. Of all the cases in which the vertebral lesion was operated upon, 19 per cent revealed increase in kyphosis by 10 degrees or more. The diseased area radiologically revealed osseous replacement in 89 per cent and fibro-osseous in 1 1 per cent of cases. Because the results obtained by the middle-path regime compare favourably with those of radical operation, it is suggested that triple drug therapy should be used in the first instance. Operative treatment is suggested for failure, recrudescence or complication. My thanks are due to Mr D. K. Mathur and Mr S. P. Singh for illustrations and to Mr P. K. Mukherji and Mrs Swam for secretarial help. REFERENCES American Thoracic Society. The Sub-Committee on Surgery and the Committee on Therapy (1963) The present status ofskeletal tuberculosis. American Review of Respiratory Diseases, 88, Andr#{233},T. (1956) Studies on the distribution of tritium-labelled dihydrostreptomycin and tetracycline n the body. Ada radiologica. Supplement 142. Arct, W. (1968) Operative treatment of tuberculosis of the spine in old people. Journal ofbone andioint Surgery, 50-A, Bailey, H. L., Gabriel, M., Hodgson, A. R., and Shin, J. S. (1972) Tuberculosis of the spine in children. Operative findings and results in one hundred consecutive patients treated by removal of the lesion and anterior grafting. Journal of Bone and Joint Surgery, 54-A, Bakalim, G. (1960) Tuberculous spondylitis, a clinical study with special reference to the significance of spinal fusion and chemotherapy. Acta orthopaedica Scandinavica, Supplement 47. Barclay, W. R., Ebert, R. H., Le Roy, G. V., Manthei, R. W., and Roth, L. J. (1953) Distribution and excretion of radioactive isoniazid in tuberculous patients. Journal of the American Medical Association, 151, Bosworth, D. M. (1963) Modem concepts of treatment of tuberculosis of bones and joints. Annals of New York Academy of Sciences, 106, THE JOURNAL OF BONE AND JOINT SURGERY

11 RESULTS OF TREATMENT OF SPINAL TUBERCULOSIS BY MIDDLE-PATH REGIME 23 Bosworth, D. M., and Wright, H. A. (1952) Streptomycin in bone and joint tuberculosis. Journal o/bone andjoint Surgery, 34-A, Canetti, G. (1955) The Tuberc/e Bacillus in the Pulmonary Lesion of Man. New York : Springer Publishing Company, Inc. Chofnas, I., Surrett, N. E., and Severn, H. D. (1964) Pott s disease treated without spinal fusion. American Review ofrespiratory Diseases, 90, Dickson, J. A. S. (1967) Spinal tuberculosis in Nigerian children. Journal of Bone and Joint Surgery, 49-B, Falk, A. (1958) A follow-up study ofthe initial group ofcases ofskeletal tuberculosis treated with streptomycin, The United States Veterans Administration and Armed Forces Cooperative Studies of Tuberculosis. Journal of Bone and Joint Surgery, 40-A, Fell#{228}nder,M. (1955) Radical operation in tuberculosis of the spine. Acta orthopaedica Scandinavica, Supplement 19. Fell#{228}nder,M., Hiertonn, T., and Wallmark, G. (1952) Studies on the concentration of streptomycin in the treatment of bone and joint tuberculosis. Acta tuberculosea Scandinavica, 27, Fox, W. (1962) The chemotherapy and epidemiology of tuberculosis. Lancet, 2, , Fox, W. (1964) Realistic chemotherapeutic policies for tuberculosis in the developing countries. British Medicalfournal, 1, Friedman, B. (1966) Chemotherapy of tuberculosis of the spine. Journal ofbone andjoint Surgery, 48-A, Girdlestone, G. R. (1965) Tuberculosis ofbone andjoint. Third edition revised by E. W. Somerville and M. C. Wilkinson. London: Oxford University Press. Hald, J. (1955) Treatment of bone and joint tuberculosis with streptomycin and PAS. Acta tuberculosea Scandinavica, 30, Hanngren, A. (1959) Studies on the distribution and fate ofc 14- and T-labelled p-aminosalicylic acid (PAS) in the body. Acta radiologica, Supplement 175. Hanngren, A., and Andr#{233}, T. (1964) Distribution ofa 3 H-dihydro-streptomycin in tuberculous guinea-pigs. Acta tuberculosea etpneumologica Scandinavica, 45, Hev#{233}r, E., and Risko, T. (1960) Studies on streptomycin levels of blood and abscess. Acta tuberciilosea Scandinavica, 38, Hodgson, A. R., and Stock, F. E. (1960) Anterior spine fusion for the treatment of tuberculosis of the spine. Journal of Bone and Joint Surgery, 42-A, Hodgson, A. R., Stock, F. E., Fang, H. S. Y., and Ong, G. B. (1960) Anterior spinal fusion: the operative approach and pathological findings in 412 patients with Pott s disease of the spine. British Journal ofsurgery, 48, Kaplan, C. J. (1959) Conservative therapy in skeletal tuberculosis: an appraisal based on experience in South Africa. Tuhercle (London), 40, Katayama, R., Itami, Y., Oya, K., Tanaka, J., and Maruno, E. (1954) The chemotherapy of bone and joint tuberculosis. II. Observations on clinical diseases. Annals of Tuberculosis, 5, Kirkaldy-Willis, W. H., and Thomas, G. T. (1965) Anterior approaches in the diagnosis and treatment of infections of the vertebral bodies. Journal of Bone and Joint Surgery, 47-A, Kohli, S. B. (1967) Radical surgical approach to spinal tuberculosis. Journal ofbone andjoint Surgery, 49-B, Kondo, E., and Yamada, K. (1957) End results of focal d#{233}bridement in bone and joint tuberculosis and its indications. Journal of Bone andjoint Surgery, 39-A, Konstam, P. G. (1963) Spinal tuberculosis in Nigeria. Annals ofthe Royal College ofsurgeons ofengland, 32, Konstam, P. G., and Blesovsky, A. (1962) The ambulant treatment of spinal tuberculosis. British Journal ofsurgery, 50, Konstam, P. G., and Konstam, S. T. (1958) Spinal tuberculosis in Southern Nigeria, with special reference to ambulant treatment of thoraco-lumbar disease. Journal of Bone and Joint Surgery, 40-B, Lindberg, L. (1967) Experimental skeletal tuberculosis in the guinea-pig. A method for producing local lesions and autoradiographic study of their accessibility to tritium-labelled dihydrostreptomycin. Acta orthopaedica Scandinavica, Supplement 98. Martin, N. S. (1970) Tuberculosis of the spine. A study ofthe results oftreatment during the last twenty-five years. Journal ofbone and Joint Surgery, 52-B, Masalawala, K. S. (1963) Operative treatment in tuberculosis of the spine. Indian Journal ofsurgery, 25, Orell, S. (1951) Chemotherapy and surgical treatment in bone and joint tuberculosis. Acta orthopaedica Scandinavica, 21, Paus, B. (1964) Treatment for tuberculosis of the spine. Acta orthopaedica Scandinavica, Supplement 72. Puig Gun, J. (1947) The formation and significance of vertebral ankylosis in tuberculous spines. Journal of Bone and Joint Surgery, 29, Risks, T., and Novoszel, T. (1963) Experiences with radical operations in tuberculosis ofthe spine. Jour,zal ofbone andjoint Surgery, 45-A, Roaf, R., Kirkaldy-Willis, W. H., and Cathro, A. J. M. (1959) Surgical Treatment of Bone and Joint Tuberculosis. Edinburgh : E. & S. Livingstone Ltd. Stevenson, F. H., and Manning, C. W. (1962) Tuberculosis of the spine treated conservatively with chemotherapy: series of 72 patients collected , and followed to Tubercie (London), 43, Stock, F. E. (1962) Anterior spinal fusion. Review of 5 years work. Australian and New Zealand Journal of Surgery, 31, Tuli, S. M. (1969) Treatment of neurological complications in tuberculosis of the spine. Journal ofbone andjoint Surgery, 51-A, Tuli, S. M. (1973) Treatment of tuberculosis of the spine-a review. Indian Journal ofsurgery, 35, Tuli, S. M., Brighton, C. T., Morton, H. E., and Clark, L. W. (1974) Experimental induction of localised skeletal tuberculous lesions and accessibility of such lesions to antituberculous drugs. Journal of Bone and Joint Surgery, 56-B, Tuli, S. M., and Kumar, S. (1971) Early results oftreatment of spinal tuberculosis by triple drug therapy. Clinical Orthopaedics and Related Research, 81, Tuli, S. M., Srivastava, T P., Varma, B. P., and Sinha, G. P. (1967) Tuberculosis of spine. Acta orthopaedica Scandinavica, 38, Wilkinson, M. C. (1950) Curettage of tuberculous vertebral disease in the treatment of spinal caries. Proceedings ofthe Royal Society of Medicine, 43, Wilkinson, M. C. (1955) The treatment of tuberculosis of the spine by evacuation of the paravertebral abscess and curettage of the vertebral bodies. Journal of Bone and Joint Surgery, 37-B, Wilkinson, M. C. (1969) Tuberculosis of the spine treated by chemotherapy and operative d#{233}bridement. Journal ofbone andjoint Surgery, 51-A, Yeager, R. L. (1963) Current state of tuberculosis. Opening remarks. Annals ofthe New York Academ; ofsciences, 106, 3-4. VOL. 57-B, No. I, FEBRUARY 1975