Spinal intramedullary tuberculosis: A series of 15 cases

Clinical Neurology and Neurosurgery 111 (2009) 115–118

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Spinal intramedullary tuberculosis: A series of 15 cases Shashank R. Ramdurg, Deepak Kumar Gupta ∗ , Ashish Suri, Bhavani Shankar Sharma, Ashok Kumar Mahapatra Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India

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Article history: Received 10 February 2008 Received in revised form 31 August 2008 Accepted 4 September 2008 Keywords: Spinal intramedullary tuberculosis Intramedullary lesion Spinal tuberculosis

a b s t r a c t Objectives: Spinal intramedullary tuberculosis is a rare disease. This study aims to acquaint readers with its clinicoradiological features and emphasizes the importance of early treatment in intramedullary spinal tuberculosis. Materials and methods: Retrospective analysis was conducted from 1985 to 2006 over a period of 21 years and data were retrieved from patient records at our institute (single centre study). Clinicoradiological and pathological data were reviewed along with final outcome at discharge and analyzed. Results: Fifteen patients were analyzed. Mean age of presentation was 31 years (range: 18–45 years), with average duration at presentation being 11 months (2–24 months). Common locations: dorsal region: 7 cases, cervical: 5 cases, cervicodorsal: 2 cases and dorsolumbar region: 1 case. Sensori-motor involvement was noted in fourteen patients. Bowel and bladder involvement was seen in ten patients while one patient had respiratory distress. Only 40% of patients had secondary involvement of spine while the rest of the cases were having primary spinal intramedullary tuberculosis. Three patients had previous history of tubercular meningitis, while one patient had old pulmonary tuberculosis. There were one case each of cervical node involvement and intracranial granuloma. Twelve patients underwent surgery while others were conservatively managed, all patients received antitubercular therapy for 18 months. Nine of the twelve operated patients showed improvement in motor power, while two of the conservatively managed patients improved. Patients presenting late had a poorer outcome. Conclusion: Spinal intramedullary tuberculosis is a non-malignant, treatable lesion giving a good outcome on management. Surgically managed patients showed a better outcome. © 2008 Published by Elsevier B.V.

1. Introduction Tuberculosis is the one of the commonest endemic disease in India. Involvement of central nervous system (CNS) tuberculosis constitutes up to 10–15% of all tuberculous infections [1]. CNS involvement of tuberculosis is one of the most feared complications as it is associated with high rates of morbidity and mortality, even in those patients who are adequately treated [2]. Cases of tuberculosis involving spine are rare (ratio of involvement of spine:brain = 1:42) [2]. Spinal tuberculosis usually presents as tuberculous spondylitis or arachnoididts. Involvement of intramedullary portion is unusual [3–7]. Since first described by Abercrombie in 1828 [8], there have been multiple isolated case reports or short series of this rare disease. With a rising incidence of human immunodeficiency virus

∗ Corresponding author at: 714, Neurosciences Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India. Fax: +91 11 26589650. E-mail addresses: dkg [email protected], dg [email protected] (D.K. Gupta). 0303-8467/$ – see front matter © 2008 Published by Elsevier B.V. doi:10.1016/j.clineuro.2008.09.029

(HIV)/acquired immunodeficiency syndrome (AIDS) there is likely to be a concurrent rise in the exposure of neurosurgeons all over the world to this uncommon entity. However due to the absence of routine screening for immunosuppressive states, it is difficult to ascertain the actual incidence of such diseases as HIV in spinal intramedullary tuberculosis. Although a treatable entity, delay in diagnosis is also associated with significant morbidity [9]. However a lack of large series and analysis has precluded a proper analysis of this disease. To our knowledge this is the largest series of spinal intramedullary tuberculosis reported in English literature. 2. Materials and methods This is a retrospective study at our institute, conducted over a period of twenty one years (1985–2006). Fifteen patients of spinal intramedullary tuberculosis were treated at our institute during this period. Data pertaining to these patients were retrieved from patient records. Clinical, radiological and pathological data were reviewed along with final outcome at discharge. Investigations included routine hemogram (including erythrocyte sedimentation

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Table 1 Clinical data of patients suffering from spinal intramedullary tuberculosis. S. no 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Age/sex 25/f 22/m 33/f 22/m 45/f 25/m 40/m 18/m 30/m 37/f 35/f 35/f 26/m 41/f 30/f

Site C2-D4 D4-D6 C6-C7 D11-L1 D4-D5 C2-C3 D9-D12 D2-D9 D9-D11 C2-C4 D5-D6 D4-D5 C7-D1 C2-C6 C2

Clinical features (M, S, B/B, C) M, S M/S M, S, B/B M, S, B/B C M, S, B/B M/S M, S, B/B M/S M, S, B/B M, S, B/B M, S, B/B M, S, B/B, C M, S, B/B, C M, S, B/B

Investigation modalities *

NCCT , CT Myelo NCCT, CT Myelo NCCT head/spine, CT Myelo+ MRI*** spine NCCT, CT Myelo+ MRI spine NCCT/MRI brain, MRI spine MRI spine MRI spine NCCT, CT Myelo, MRI spine NCCT/MRI brain, MRI spine NCCT head, MRI spine NCCT head/spine, MRI spine NCCT/MRI brain, MRI spine NCCT/MRI brain, MRI spine * NCCT/MRI brain, MRI spine + DSA*** NCCT/MRI brain, MRI spine

Associated TB

Treatment

Pulmonary kochs (old) – Cervical nodes, TBM (old) – Intracranial granuloma – – – TBM (old) – Potts spine (old) TBM (old) – – –

Surgery Surgery Conservative Surgery Conservative Surgery Surgery Surgery Surgery Surgery Surgery Surgery Surgery Conservative Surgery

Abbreviations: Age: in years; Sex: m, male; f, female; Site: C, cervical; D, dorsal/thoracic; L, lumbar; Clinical features—M, motor involvement; S, sensory involvement; B/B, bowel and bladder involvement; C, constitutional symptoms like pain, fever; TBM, tubercular meningitis. All patients underwent other systemic examinations like C-X-ray, ultrasound abdomen, urine examination to rule out other sources of dissemination. Note: IADSA was done to rule out vascular pathology. Cranial investigations obtained to rule out intracranial lesions. Patient was started on antitubercular therapy to which patient responded. ** MRI—Magnetic resonance imaging. * NCCT—Non-contrast computed tomography. *** IADSA—Intra-arterial digital subtraction angiography.

rate, ESR) and serum biochemistry. Human immunodeficiency virus testing was done in 5 cases (negative in all). Chest X-ray, ultrasound abdomen and urine analysis were done to rule out source of infection. Six patients had non-contrast computed tomography (NCCT) spine. Five patients underwent CT myelography and thirteen patients had magnetic resonance imaging (MRI) spine. Nine patients also had a NCCT/or MRI brain. Three patients were conservatively managed on antitubercular therapy (ATT) alone (given for 18 months while rest underwent laminectomy with decompression of abscess/tuberculoma with postoperative antitubercular therapy for 18 months. Biopsy was obtained on all surgically operated cases. Postoperatively all patients received a short course of steroids in the form of dexamethasone/methyl predniosolone, which was rapidly tapered off. All patients were started on antitubercular therapy to be received for 18 months duration (4 drugs (RHEZ, rifampicin 10 mg/kg body weight, isoniazid 5 mg/kg body weight, ethambutol 15 mg/kg body weight and pyrazinamide 25 mg/kg body weight) for 6 months and 2 drugs (Rifampicin and Isoniazid for 12 months). 3. Results The patients age ranged from 18 to 45 years (mean = 31 years). The male to female ratio was 7:8 with slight female preponderance, in contrast to most previous studies [2–7]. The duration of symptoms before presentation was 2 months to 24 months (mean 11 months). Most common location was in the dorsal region with seven cases. Five cases had cervical involvement, two cases cervicodorsal region, while there was one case of dorsolumbar spinal intramedullary tuberculosis (Table 1). 3.1. Symptomatology The most common modality of presentation was in the form of sensory-motor involvement in fourteen patients (94%). Motor involvement was in the form of asymmetric weakness, paraparesis or even quadriparesis. Sensory symptoms included numbness or paraesthesias with many patients exhibiting dissociative sensory loss. Ten patients (66.67%) had some form of urinary symptoms in the form of absent bladder sensations, incontinence or increased frequency. One patient (6.7%) had respiratory distress, who was

tracheostomized postoperatively for respiratory support/care. Six of the fifteen patients (40%) had evidence of tuberculosis elsewhere in the body. Three patients had cranial involvement in the form of tubercular meningitis while intracranial granuloma, cervical nodal involvement, pulmonary tuberculosis, Pott’s spine were found in one case each. 3.2. Investigations MRI was the chief investigation modality used. Lesions were usually hypo intense on T1W and iso-to-hyper intense in T2W images. Lesions were usually heterogeneous in nature with cord expansion. Ring enhancement was seen in six patients. Others showed heterogeneous enhancement. Three patients demonstrated multiple lesions. Three patients had associated syrinx. Nine patients had associated some degree of leptomeningeal enhancement. NCCT/MRI brain done in ten patients revealed an intracranial tuberculoma in one patient only (Figs. 1 and 2). 3.3. Treatment and follow up Three patients were conservatively managed. Two patients had intracranial involvement while one had high cervical cord involvement. Two of the patients showed some improvement, while one patient continued to remain quadriplegic. It was also observed that those patients that did not improve where predominantly those who presented late. Rest of the cases underwent laminectomy and decompression of the abscess/tuberculoma. Cord was expanded in majority of cases to variable degree with lack of clear cut demarcation of the lesion. Nine of the operated patients showed some degree of improvement while three patients stabilized neurologically. Student T-test was used to compare the outcome in conservatively managed and surgically treated patient group, however, the difference was not statistically significant barring the better outcome in more number of cases in surgically/early treated group than in conservatively managed patients. All patients received ATT for a period of 18 months. Regimen included INH, rifampin, pyrazinamide and ethambutol. Antituberculous treatment comprised 4 drugs for 6 months (Isoniazid 5 mg/kg body weight, Rifampicin 10 mg/kg body weight, Ethambutol 15 mg/kg body weight and Pyrazinamide 25 mg/kg weight) After 6 months, all

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Fig. 3. Histopathology slide showing epitheloid cell granuloma (magnification 40×).

Fig. 1. T1W sagittal image of MRI showing cervical intramedullary tuberculoma.

patients received Isoniazid and Rifampicin for next 12 months. All patients had weekly liver function tests for the first one month of therapy and subsequently every 3 monthly (serum bilirubin, serum transaminases (SGOT/SGPT) and alkaline phosphatase), ESR (Erythrocyte sedimentation rate). All patients had ophthalmological evaluation 6 months and 12 months after initiation of therapy to look for ethambutol toxicity. 3.4. Pathological examination All operated cases had histopathological analysis of the biopsy specimen to look for the presence of granulomas/caseous necrosis/presence or absence of tuberculous bacilli. AFB and Gram’s staining and AFB and bacterial culture analysis was done in all oper-

Fig. 2. T1W contrast image of cervical intramedullary tuberculoma showing enhancement with central isodense core.

ated cases. Only one patient had AFB positive culture. None of the patients were positive for secondary bacterial infections. Biopsy revealed granulomatous lesions with or without caseation necrosis. Granulomas were characterized by lymphoid cells with foreign and Langhans type giant cells (Fig. 3). 4. Discussion The incidence of spinal tuberculosis is estimated to be 1 percent of all cases of skeletal tuberculosis [9,10]. Intramedullary involvement is very rare. Since its first description by Abercrombie in 1928 [8], there have been many isolated case reports or short series. True epidemiological and clinical profile thus has been elusive to study. With increasing incidence of AIDS, and resurgence of tuberculosis, a corresponding increase in such rarer modalities of presentation is also likely to increase. Intramedullary tuberculosis often afflicts the young adults, thus affecting the productive population of any country. Though there is a reported male predominance in previous studies [11,12], no such sex difference was seen in the current study. This in all probability may be due to increasing female literacy, health awareness in developing nations like India. Thoracic region is the most common site of involvement (7 cases in our series). This is followed by cervical (5 cases), cervicodorsal and dorsolumbar regions. Though multiple sites of involvement are well documented in literature (in 10–33%), they are uncommon and sparsely reported [10,13]. Presentation is highly varied. They usually present as sub acute neoplastic intramedullary space occupying lesions [14–16]. Manifestation depends on site and extent of the lesion. Most common involvement in our series was sensory-motor involvement (93%) in our series. Motor involvement was in the form of asymmetric weakness, paraparesis and quadriparesis. Sensory symptoms included numbness or paraesthesias. Many patients have dissociative sensory loss. Bowel and bladder involvement usually occur late. Constitutional symptoms like fever, weight loss may not be the presenting complaint in intramedullary tuberculosis as compared to pulmonary tuberculosis wherein the constitutional symptoms are very common. In case of involvement of higher cord/cervical levels more dramatic presentation in the form of respiratory distress can occur [12]. Previous studies have well documented the association with pulmonary tuberculosis. In our study we however did not find such an association. Intracranial tuberculosis was seen in four cases, with three cases of treated tubercular meningitis, while one patient had intracranial granuloma. Pulmonary tuberculosis, nodal

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involvement and Pott’s spine was seen in one case each. In a series by Indira devi et al. [15] pulmonary tuberculosis was detected in majority of cases. Concurrent occurrence of intracranial lesions has also been well documented in literature. Radiological investigation of choice is MRI spine (whole spine). First MRI documented description was given by Rhoton et al. in 1988 [13]. The differential diagnosis includes neoplastic, inflammatory, demyelinating, vascular and granulomatous lesions. Lesions are usually hypo intense on T1W images and iso-to-hyper intense on T2W images. Definitive features of cord expansion exist. They may have heterogeneous or ring enhancing lesions depending on the presence or absence of caseation necrosis [17,18]. X-ray and CT spine better delineate associated bony pathologies, if any. In pre MRI era CT myelography was often used for investigation. Workup of any patient should also include seeing for primary source of infection like Chest-ray, USG abdomen-pelvis, urine examination. Definitive diagnosis however rests on tissue biopsy. Biopsy shows granulation tissue with predominant lymphoid cells, with foreign body or Langhans type giant cells. Caseation may or may not be present in all cases. AFB staining and culture is often negative as was noted in our series. The incidence of extra pulmonary tuberculosis is also reported to be as high as 70% in patients infected with HIV. However, due to the absence of routine screening for HIV in these patients, the incidence of coexistence of both diseases is likely to be missed. Hence the prevalence of intramedullary lesions cannot be definitively ascertained in patients with AIDS. Gupta et al. [19] reported 10 cases that they managed conservatively. Similar findings were reported by other authors [14]. However progression of disease despite adequate antitubercular therapy is well documented [20]. Hence at our institute, we believe that surgical biopsy is essential as in many cases a preoperative diagnosis may be difficult. Surgical decompression aids a faster excision recovery when combined with 18 months of chemotherapy, along with antiedema measures/steroids. However due to paucity of literature on spinal intramedullary tuberculosis, such comment is at best our opinion in this regard. Decompression allows for better drug action, rapid relief from pressure symptoms. However, in a few cases, where surgical excision is hazardous, medical treatment with ATT may be the only viable option. Patients presenting with acute neurological deterioration/not showing any improvement with antitubercular therapy and bladder/bowel involvement, should be offered early surgical intervention for better neurological outcome. 5. Conclusion Spinal intramedullary tuberculoma is a rare form of spinal tuberculosis. It is a benign condition with good prognosis with

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