Preliminary Study of Tuberculosis of the Spine

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1 Original Articles Preliminary Study of Tuberculosis of the Spine Robert C. Lifeso, MD, FRCS(C)* * Orthopedic Surgeon, Department of Surgery, King Faisal Specialist Hospital and Research Centre ABSTRACT Tuberculosis of the spine is a common problem in Saudi Arabia. Sixty-two patients with this condition presented to the King Faisal Specialist Hospital and Research Centre between June 1978 and July Thirty-six of the 62 patients presented with tetraparesis or paraparesis. Thirty-two percent of neurologically impaired patients improved with chemotherapy and all but three of the remainder recovered following anterior decompression and fusion. The remaining 26 patients were ambulatory upon admission; 68 percent of these patients recovered with chemotherapy alone and 32 percent recovered with anterior decompression in addition to chemotherapy. Anterior decompression and fusion is recommended in spinal tuberculosis for (1) biopsy, (2) failure of conservative treatment, and (3) instability. RC Lifeso, Preliminary Study of Tuberculosis of the Spine. 1982; 2(1): 3-12 KEYWORDS: Tuberculosis, osteoarticular, Spinal diseases, Spinal fusion Introduction Tuberculosis, although a disease of antiquity, is still all too prevalent in many areas of the world. 1 It is estimated that there may be as many as 20 million infectious cases of tuberculosis worldwide today. 2 Tuberculous involvement of the spine, although relatively uncommon, is often one of the most serious and dangerous manifestations of the disease. It is frequently accompanied by neurological sequelae and death. Adams, in 1940, reported a 40 percent mortality rate in children with spinal tuberculosis, whether treated conservatively or with posterior spinal fusion. 3 Swift, also reporting in 1940, showed a 28 percent mortality rate following posterior spinal fusion. This study included 584 patients, 57 percent under the age of ten years. 4 The introduction of chemotherapy in the early 1950s did affect the mortality rate but had little effect on the rate of paraparesis. 5 The mortality rate among patients with spinal tuberculosis fell from approximately ten percent to three percent but the rate of paraparesis remained constant at about 20 percent of all cases of spinal tuberculosis. 5 The first, major improvement in this dismal picture was reported from Hong Kong where anterior decompression and fusion were performed on all patients with spinal tuberculosis. 6 In their first 100 cases, healing with bony ankylosis occurred in 93 percent with an overall mortality rate of four percent. Thirty-five of these first 100 patients were paraparetic and 74 percent of these made complete recoveries following anterior decompression and fusion. Among this group, there was a six percent mortality rate. Over the past 18 years, the Medical Research Council of England (MRC) has been carrying out a prospective study of spinal tuberculosis in various centers throughout the world. Their results suggest that 82 to 88 percent of all patients receiving chemotherapy alone will achieve a favorable result over a three-year period. 7 A favorable result means: no drainage, ability to work, and spinal stability. This stabilty was due to bony ankylosis in 68 percent of cases. These authors' results suggest that other forms of treatment such as bed rest, plaster jackets, and surgical debridement without fusion had little effect on the end results. Chemotherapy using isoniazid, para-aminosalicylate (PAS), and streptomycin was found to be no more effective than chemotherapy without streptomycin. 7 It is difficult to compare the results of the MRC study with the results of other studies, specifically concerning the paraparetic patient. The MRC study did not include patients who were nonambulatory. The Hong Kong portion of the MRC study did not include patients having three or more vertebral bodies involved and in Hong Kong the majority of patients were children under the age of ten years. In this preselected group, the MRC did achieve an 82 to 88 percent satisfactory result over three years but with an average increase in kyphosis of 15 and a failure rate of 12 to 18 percent. The MRC recommends early operative treatment for the neurologically impaired patient, specifically radical debridement and anterior fusion, if the facilities are available. 11 It is difficult to compare studies from various parts of the world. The disease seems to affect different populations in widely diverse ways. In the MRC study, 40 percen' of all patients were under the age of ten years, whereas in Europe tuberculosis is primarily a disease of adults. The average age of patients from the Royal National

2 Orthopaedic Hospital in Stanmore, England suffering from spinal tuberculosis is 37.6 years. 12 Similarly in Ireland, it is adults, not children, who are generally affected. 13 The physician treating spinal tuberculosis is, therefore, faced with a difficult, and seemingly contradictory choice. The MRC study, on the one hand, suggests approximately 85 percent of patients with spinal tuberculosis will improve without surgery. On the other hand, the group advocating anterior debridement and fusion claim better results, faster healing, and resolution of paraparesis with surgery. All of these previous papers have recommended the use of a combination of isoniazid, PAS, and streptomycin as standard chemotherapy. To date, there are no results on the efficacy of isoniazid, rifampin, and ethambutol in spinal tuberculosis. This paper is an attempt to distinguish between those cases of spinal tuberculosis which will require surgery and those which can be safely treated with chemotherapy combining isoniazid, rifampin, and ethambutol. Methods All cases of tuberculosis of the spine referred to King Faisal Specialist Hospital and Research Centre and seen by the author between June 1978 and July 1980 have been included. The minimal follow-up period has been one year. All patients underwent standard investigations including complete blood count (CBC), erythrocyte sedimentation rate (ESR), SMAC-20 blood analysis, PPD tuberculin skin test, and radiograph of the chest and specific spinal lesions. Special studies included bone scan, tomography, myelography, and computed tomographic (CT) scan which were utilized as clinically indicated. Follow-up examinations were all performed by the author. All proven cases of spinal tuberculosis were originally treated with full dosages of isoniazid, rifampin, ethambutol, and pyridoxine. The majority of cases presenting with tetraparesis or paraparesis had been on such regimens elsewhere, many for three to six months without improvement. Surgery was reserved for those cases in which: (1) the diagnosis was in doubt, (2) there had been a failure of medical management, or (3) there was either early or late instability. Instability was judged by the amount of bony destruction and displacement at initial presentation or, in the late cases, by continuing movement and pain after at least three to six months of adequate chemotherapy. Figure 1A and B. Lack of clinical improvement in the neurologically impaired patient after two to three weeks of chemotherapy was an indication for surgery. This period was chosen empirically at the beginning of the series. After we had gained some experience in the problem, surgery was advocated immediately if radiographic examination showed a localized mechanical block due to spinal displacement or protrusion of bone or disc not likely to respond to chemotherapy. Patients with blocks due to widespread disease or arachnoiditis were not operated upon. Figure 2A and B. In the ambulatory patient, the minimum period of chemotherapy was three months; however, in this group I generally wait six months before advocating surgery. Surgical Approaches Involved cervical vertebrae were approached through a standard anterior incision between the carotid sheath and the trachea. Thoracic vertebrae were approached via a right thoracotomy incision unless radiographic examination showed that abscess and bone destruction was greater on the left. In that case, left thoracotomy was performed. The cervicothoracid junction was approached either through the right third rib or through a low anterior cervical spine approach, depending upon the extent of the disease.

3 Figure 1 A. A 38-year-old woman with a four-year history of untreated cervical spine tuberculosis, B. The same patient five months following anterior decompression and fusion. Thoracolumbar lesions were usually approached through the chest and then turning down the diaphragm as required. Lumbar lesions were approached via a standard retroperitoneal procedure. Results Seventy-three cases were referred for evaluation with the initial diagnosis of tuberculosis of the spine; however, only 62 of these patients were finally proven to have tuberculosis. The average age of the patient in the group with confirmed tuberculosis was 39 years. There were 24 female and 38 male patients. Our youngest patient was 12 years of age. The remaining 11 patients, originally referred to the Hospital with a presumptive diagnosis of tuberculosis, were found on biopsy to have other diseases. The average age of this group was 34 years. Table 1. Figures 3 and 4. Of the 62 patients with tuberculosis, 50 percent had tuberculous lesions in the thoracic spine, 25 percent in the lumbar spine, 13 percent in the cervical spine, and 8 percent at the thoracolumbar junction. Five percent had extradural lesions without initial evidence of bone involvement. This five percent all presented with paraparesis or tetraparesis. Table 2. Table 3 shows the percentage of cases at each spinal level initially presenting with paraparesis or tetraparesis. Tetraparesis or paraparesis implied that the patient was unable to stand or walk because of neurological involvement. Patients classified as nonparetic were all able to walk although many exhibited some degree of motor or sensory deficiency. This excludes cases without bony foci, with widespread arachnoiditis, or with multiple disease foci. One patient with involvement at the C/C 2 level died before treatment could be started.

4 Figure 2. A. Widespread tuberculous arachnoiditis showing complete myelographic block at the L 4 level, without bony involvement. B. Cisternal myelogram showing complete block at the T 4 level, without bony involvement. Standard investigation of the patients with tuberculosis revealed that 84 percent of patients had positive skin tests for tuberculosis; 95 percent had ESR rates greater than 30 mm; all had normal hemoglobin and white blood cell counts; all had normal SMAC-20 blood analyses; and radiographs of 95 percent showed bony lesions. The three cases without bony lesions presented with paraparesis or tetraparesis, and all had extradural lesions as seen on myelography

5 Figure year-old girl with complete paraplegia. Note bone destruction plus large, soft tissue mass. The mass was proven, by biopsy, to be an aneurysmal bone cyst. Recovery was complete following anterior decompression and strut graft. Myelographs were performed on 25 patients. Ninety-two percent of the cases with tetraparesis or paraparesis showed complete or incomplete obstruction of the spinal canal. Bone scan results were positive in 62 percent of patients and were equivocal in 38 percent. Gallium scanning was per- formed in only three cases and was negative in two and equivocal in one. Table 1. Other causes of spinal lesions Tumor No. of patients Sepsis No. of patients Other Paraganglioneuroma 1 Brucella 1 Arterio-venous malformation 1 Aneurysmal bone cysts 3 Staph aureus 1 Meningioma 1 E. coli 1 Metastatic thyroid 1 Enterobacter 1 cancer 6 cloacae 4 1

6 Figure 4. A 25-year-old woman with destruction of the body of T 6 and complete paraplegia. Biopsy results indicated paraganglioneuroma. There was no recovery following anterior decompression and fusion. Needle biopsies were performed on 12 patients and were diagnostic in ten with one false positive and one false negative result. Thirty-six patients were unable to stand or walk when first seen, because of neurological involvement. Twentyfive have been followed for at least one year. Eleven other patients failed to follow the suggested treatment plan and have not been included in the results. Eight of the 25 patients recovered on chemotherapy alone such that surgical treatment was not required. The average duration of paraparesis in this group was three months before the initiation of treatment. On the average, these patients were able to walk again seven and one-half months after treatment was started. Seventeen of 25 paraparetic patients did not respond to chemotherapy and underwent anterior debridement and fusion. Figure 5a and b. In this group, the average duration of preoperative paraparesis was six months and 14 of 17 patients were walking in an average of 3.6 months after surgery. Table 4. Table 2. Location of disease in tuberculosis Number of Percentage Location patients of all TB C 1-C T 1-T T 7-T T 12-L L 2-L Extradural

7 Table 3. Percentage of cases of TB presenting with para or tetraparesis at various spinal levels* Location Total number of patients Percentage of para or tetraparetic patients C 1-C T 1-T T 7-T L 1-L * Excludes cases with widespread arachnoiditis and multiple disease foci. Three patients did not respond to surgery. The first was a 31 -year-old male who had had a posterior laminectomy elsewhere and had suffered a cord infarction. The second patient was a 78-year-old man who had paraparesis for 11 months before surgery. He did recover bowel and bladder control and sensation but is still unable to walk. The third patient was operated on 27 months after the onset of paraparesis and is now able to walk with the use of long-leg braces. Twenty-six patients with spinal tuberculosis were ambulatory when first seen and have been followed for more than one year. One patient failed to complete the treatment course and is excluded. Eight patients in this group eventually required anterior fusion because of continuing disease activity or persisting instability and pain. Six of these patients achieved solid fusion. One patient, who underwent anterior decompression and stabilization with rib graft struts, did not fuse and another was fusing at the time surgery was performed. This patient most probably would have healed without surgery. None of the patients, who were ambulatory upon presentation, worsened while on chemotherapy or following surgery. Figure 5. A. A 55-year-old man with complete paraplegia for three months. Preoperative radiograph shows involvement of thoracic bodies T 8 _ 11. B. The same patient six months after surgery showing healing with bony ankylosis and resolution of paraplegia. The strut of iliac crest is visible from T 8_11.

8 Table 4. TB paraparesis Duration of Time to Number of paraparesis walking patients Treatment (months) (months) 8 Recovered with chemotherapy alone Recovered after surgery Four patients developed paraparesis an average of eight years after previous treatment for tuberculous spinal disease. One developed severe arachnoiditis and paraparesis; she regained her ability to walk after being treated with chemotherapy only. Two patients had evidence of old disease with recurrence at different sites. Both recovered following anterior surgical decompression. The fourth patient showed a new focus plus diffuse arachnoiditis, and she recovered on chemotherapy only. Figure 6a and b. Table 1 shows 11 cases initially referred as tuberculosis but biopsy results revealed other diseases. Eight of these patients underwent anterior biopsy, decompression, and fusion; three underwent needle biopsy. All fusions were solid within one year. Ten patients had undergone surgery elsewhere. Six had undergone posterior decompression; three of the six developed postoperative paraparesis, and three remained unchanged. Four patients had undergone anterolateral decompression; two became worse as a result of surgery and two improved. Of the 36 cases who underwent anterior decompression and fusion, 84 percent improved and none worsened. Table 5. The six patients who failed to improve with anterior decompression included five with tuberculosis, previously discussed, and one case of paraganglioneuroma which achieved bony ankylosis without neurological improvement. Figure 6. A. Healed focus of tuberculosis with new focus of disease with widespread arachnoiditis. B. After one year of chemotherapy alone the new foci have fused and paraplegia has resolved.

9 Biopsy specimens taken at surgery in tuberculosis cases gave the following results: (1) pathology, positive in 73 percent; (2) smear, positive in 70 percent; (3) cultures, positive in 43 percent. There were no resistant organisms. Complications There was one death due to tuberculous involvement at the C 1 /C 2 level. Death occurred before treatment could be initiated. In the operative series, one patient suffered a nonfatal pulmonary embolus. Four patients either fractured or displaced their grafts, only one of which required reoperation. Figure 7A, B, C, and D. The remaining patients did well without serious complications; there was no secondary infections or draining sinuses. There were no operative deaths. Table 5. Results of surgery Surgical approach Worse Same Better Anterior Postero-lateral Posterior Discussion Spinal tuberculosis is not an uncommon disease in Saudi Arabia. The age of involvement is more similar to that seen in Europe rather than the age group usually seen in Asia or Africa. Severe neurological involvement was seen in 36 of 62 patients with spinal tuberculosis in this series. This is a much higher figure than reported elsewhere but it probably indicates that less severely affected cases respond to conservative treatment and only those failing to respond were referred to this Hospital. Thirty-one patients had lesions in the thoracic spine and 25 of these were referred for evaluation of paraparesis. The most dangerous area of the spine for neurological problems in our series is between the first and sixth thoracic vertebrae. Figure 8A and B. This may be due to the small diameter of the spinal canal in this area or, perhaps, the blood supply to the cord in this region makes it more vulnerable to injury. The cervical spine was involved in 13 percent, 50 percent had tetraparesis on presentation. The lumbar spine is remarkably stable and only one patient with tuberculosis in this area developed paraparesis; in this case the paraparesis was incomplete. Eleven cases referred as tuberculosis were eventually found to have other diseases. The importance of early biopsy in all cases of suspected tuberculosis failing to respond to chemotherapy and in all cases where the clinical and radiographic appearances leave doubt as to etiology cannot be overemphasized. The diagnosis is often clinically difficult. The PPD skin test was negative in 16 percent of patients, ESR was elevated in 95 percent but was nonspecific. Complete blood count and SMAC-20 blood analysis are of little value in differentiating tuberculosis from other septic processes or tumors. The value of needle biopsy has been equivocal. If positive, it can be extremely valuable; when negative, it must be followed by open biopsy.

10 Figure 7. A. A 28-year-old woman with complete quadriplegia for three months shows preoperative destruction at C 5 _ 7. B. The same patient following anterior decompression and strut at C 5 -T 1. c. One month after surgery the patient shows neurological improvement in standing status. Graft has extruded without neurological sequelae. D. The patient was ambulatory five weeks after the second operation with larger graft at C 4 -T 1.

11 Figure 8. A. A 16-year-old girl with complete paraplegia for three months. There is destruction of the upper thoracic spine with loss of two complete bodies and posterior displacement of bony sequestra (arrow). B. The same patient following decompression and strut grafting with removal of bony sequestra. Three cases presenting with profound neurological deficits had, initially, normal spinal radio-graphs. Myelography revealed extradural defects in all cases, which were proven by surgery to be tuberculosis. Myelography is extremely valuable in delineating the extent of obstruction in para or tetraparesis and in identifying cases of arachnoiditis which are probably not amenable to surgical treatment. All cases with severe arachnoiditis have responded well to chemotherapy alone. Of the ambulatory patients, 32 percent eventually required surgery for instability or continuing disease. In the remaining 68 percent all vertebrae fused satisfactorily, and no patient experienced neurological sequelae. In patients presenting with severe neurological impairment, 68 percent eventually required surgery. In this group, all patients operated on within nine months of the onset of paraparesis or tetraparesis experienced full recovery. The anterior approach is considered to be the surgical procedure of choice. From this approach, biopsy, decompression, and stabilization can all be safely performed. The indications for posterior decompression are: (1) posterior disease, (2) a stable spine with a localized tuberculoma causing blockage in the spinal canal, and (3) if the

12 nature of the disease is such that only biopsy is contemplated. The development of neurological sequelae years after a primary focus has healed has, in the author's experience, been due to either disease at another site or arachnoiditis or both. Kyphosis or bony bars have, in my experience, not been a cause of the late onset of paraparesis. Recurrences should be treated the same way as the primary disease. Iliac crest strut grafts appear to be more advantageous for fusion than rib grafts. Rib grafts, in my experience, tend to be slow to incorporate, fracture more readily, and often cut into adjacent vertebrae leading to subsequent recurrence of kyphosis. The average hospital stay for the surgical patient is now approximately two weeks which includes both preoperative assessment and postoperative care. Postoperative immobilization may be achieved by a simple four-poster collar for the cervical spine, a simple lumbosacral corset for the lumbar lesions, and usually nothing for thoracic lesions. All patients are mobilized as soon as possible. This is usually within the first seven days after surgery. No patient has been treated with prolonged bed rest or plaster jackets. Conclusion In spinal tuberculosis 68 percent of ambulatory and 32 percent of nonambulatory patients responded favorably to chemotherapy alone. Of the remaining patients, 88 percent benefited from surgery. The preferred surgical approach is usually anterior and, from this approach, 88 percent of all operative cases achieved stable bony ankylosis with neurological recovery. Surgery is indicated if the diagnosis is in doubt and needle biopsy is inconclusive; in lesions of the cervical spine where either early or late instability is a high probability; and in all lesions of the thoracic spine not responding rapidly to conservative treatment. Surgery may also be indicated for continuing disease activity and painful instability in spite of adequate chemotherapy. In the paraparetic patient, immediate surgical intervention is indicated if radiographic studies suggest a localized mechanical obstruction. Obstruction is usually due to a sequestered bone or disc and conservative management will not reverse that obstruction. In the nonparaparetic patient, chemotherapy with isoniazid, rifampin, and ethambutol is preferred but close follow-up must be maintained to watch for any deterioration in the neurological status of the patient. Continuing disease activity or painful spinal instability in spite of adequate chemotherapy are relative indications for stabilization. Surgical intervention is not indicated in patients with wide areas of arachnoiditis. All such cases, in my experience, have responded well to chemotherapy. REFERENCES 1. Hershfield ES: Tuberculosis in the world. Chest (Suppl) 76(6):805-ll Seddon HJ: The choice of treatment in Pott's disease. J Bone Joint Surg 58(4): Adams AB: Tuberculosis of the spine in children. A review of sixty-three cases from the Lakeville State Sanatorium. J Bone Joint Surg 22(3): Swift WE: End results of the spine-fusion operation for tuberculosis of the spine. J Bone Joint Surg 22: Martin JS: Tuberculosis of the spine. J Bone Joint Surg 52(4): Hodgson AR, Stock FE: Anterior spine fusion for the treatment of tuberculosis of the spine. J Bone Joint Surg 42(2): Leading Article: Tuberculosis of the spine. Br Med J 4(5945): Medical Research Council: A controlled trial of ambulant out-patient treatment and in-patient rest in bed in the management of tuberculosis of the spine in young Korean patients on standard chemotherapy. A study in Masan, Korea. J Bone Joint Surg 55 (4): Medical Research Council: A controlled trial of debridement and ambulatory treatment in the management of tuberculosis of the spine in patients on standard chemotherapy. A study in Botswana, Rhodesia. J Trop Med Hyg 77: Medical Research Council: A controlled trial of anterior spinal fusion and debridement in the surgical management of tuberculosis of the spine in patients on standard chemotherapy. A study in Hong Kong. Br J Surg 61 (11): Seddon HJ: The choice of treatment in Pott's Disease. (Editorial.) J Bone Joint Surg 58B (4): Kemp HB, Jackson JW, Jeremiah JD, et al.: Anterior fusion of the spine for infective lesions in adults. J Bone Joint Surg

13 55(4): Martin NS: Pott's Paraplegia: a report on 120 cases. J Bone Joint Surg 53B(4): Hodgson AR, Stock FE, Fang HSY, Ong GB: Anterior Spinal Fusion: the operative approach and pathological findings in 412 patients with Pott's disease of the spine. Br J Surg 48: