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|Year : 2014 | Volume
| Issue : 4 | Page : 409-412
Longitudinal extensive transverse myelitis due to tuberculosis: A report of four cases
SK Sahu, S Giri, N Gupta
Department of Medicine, University College of Medical Sciences (UCMS), Delhi, India
|Date of Submission||13-Feb-2014|
|Date of Decision||19-Apr-2014|
|Date of Acceptance||02-Jun-2014|
|Date of Web Publication||5-Nov-2014|
Dr. N Gupta
Department of Medicine, University College of Medical Sciences (UCMS), Delhi
Source of Support: None, Conflict of Interest: None
Tuberculosis of the central nervous system (CNS) accounts for approximately 1% of all cases of tuberculosis and half of these involve the spine. Intramedullary involvement is rare in tuberculosis and usually present in the form of radiculomyelitis, transverse myelitis, intraspinal granulomas, or thrombosis of anterior spinal artery. Transverse myelitis typically extends two or less spinal segments, whereas longitudinal extensive transverse myelitis (LETM) extends three or more spinal segments in length and may occasionally span all the segments of the spinal cord. LETM is most frequently associated with neuromyelitis optica (NMO). Moreover, associations between NMO and active pulmonary tuberculosis have been suggested by a number of case reports and case series. We present here four cases of spinal tuberculosis that presented with LETM and none of them had a clinical profile fulfilling the diagnostic criteria for NMO.
Keywords: Longitudinal extensive transverse myelitis, myelitis, neuromyelitis optica, spinal TB, tuberculosis
|How to cite this article:|
Sahu S K, Giri S, Gupta N. Longitudinal extensive transverse myelitis due to tuberculosis: A report of four cases. J Postgrad Med 2014;60:409-12
| :: Introduction|| |
According to the World Health Organization statistics for 2011, out of the estimated global annual incidence of 8.7 million tuberculosis (TB) cases, 2.2 million were from India alone. Central nervous system (CNS) TB accounts for approximately 1% of all cases of TB; half of these involve the spine. , In HIV-infected patients, the incidence of CNS TB is 10-20%.  Various presentations of spinal TB have been described in the literature, but intramedullary involvement is very rare.  Longitudinally extensive transverse myelitis (LETM) is a term designating a transverse myelitis that extends three or more vertebral segments in length, the most common cause of which is neuromyelitis optica (NMO). We present 4 cases in this paper.
| :: Case Reports|| |
A 35-year-old transgender presented with sudden-onset weakness of lower limbs and urinary retention. There was no history of root pain, back ache, fever, or trauma. The patient's vital signs and general physical examinations were normal. The CNS examinations revealed normal higher mental functions. Examination of the cranial nerves including the optic nerves revealed no abnormality. The power in both lower limbs was 0/5 according to the Medical Research Council (MRC) grade. Deep tendon reflexes were absent in bilateral lower limbs. Bilateral planters were non-responsive and abdominal reflexes were absent below T10 level. There was loss of sensation of pain and touch in the spinal segments below T10. Posterior column sensations were also absent in both lower limbs. Examination of upper limbs did not reveal any neurological deficit. Fundus examination was normal and there was no gibbus. His routine blood investigations were normal. HIV-1 serology was positive with a CD4 count of 104 cells/μl. Chest X-ray was also normal. Cerebrospinal fluid (CSF) examinations revealed 5 cells/ml (all lymphocytes), protein 75 mg/dl, sugar 48 mg/dl (blood glucose 98 mg/dl), and adenosine deaminase (ADA) 15 IU/L. Acid fast bacilli (AFB) stains were negative, but polymerase chain reaction (PCR) was positive for Mycobacterium tuberculosis. However, Gram stain, viral serology, and Indian ink preparation were negative in CSF. Magnetic resonance imaging (MRI) of the spine revealed diffuse long segment continuous centrally located intramedullary cord signal alteration extending from lower end of C7 spinal segment to the conus and appearing hyperintense on T2-weighted (T2W) images without cord expansion [Figure 1]. Contrast MRI of the brain showed multiple small ring-enhancing lesions with minimal perifocal edema in the right frontal region, left hemi midbrain and hemi pons, and cerebellar peduncle, suggestive of tuberculomas. Patient was treated with anti-tubercular treatment (ATT) comprising Isoniazid 300 mg, Rifampicin 450 mg, Pyrazinamide 1500 mg, and Ethambutol 1000 mg (HRZE). 'Methyl prednisone' 1 g was administered IV for 3 days, followed by oral prednisolone at a dose of 1 mg/kg/day. Three weeks after therapy, patient showed signs of improvement with recovery of powers and deep tendon reflexes in lower limbs. Subsequently, the patient was also started on antiretroviral therapy (ART). His neurological deficits gradually improved over 8 weeks. Now, after 1½ years of follow-up, the patient is normal without any residual neurological deficit.
|Figure 1: MRI spine showing continuous centrally located intramedullary cord signal alteration from C7 spinal segment to the conus, appearing hyperintense on T2W images without cord expansion|
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A 40-year-old female presented with acute-onset rapidly progressive weakness of lower limbs and retention of urine for 3 days. There was no history of back pain, root pain, fever, or trauma. She was a known case of type 2 diabetes mellitus with good glycemic control for the past 10 years. She was diagnosed as having miliary TB a month back and had been on anti tubercular therapy since then. On admission, patient was conscious and oriented. Vital signs and general physical examinations were normal. The CNS examination revealed normal higher mental functions and intact cranial nerves. Power in both lower limbs was MRC grade 0/5 and planter reflexes were extensor. There was loss of sensations for pain, touch, and temperature in both lower limbs in the spinal segments below L1. Posterior column sensations were also absent in both lower limbs. Examination of upper limbs did not reveal any neurological deficit. Fundus examination was normal and there was no gibbus. Routine investigations were normal including the HIV serology. Chest X-ray showed bilateral milliary mottling. CSF examination revealed 5 cells/ml (all lymphocytes), protein 40 mg/dl, sugar 152 mg/dl (blood glucose 210 mg/dl), and ADA 6 IU/L. AFB stains were negative, but PCR for M. tuberculosis was positive in the CSF. Contrast-enhanced MRI of spinal cord revealed diffuse long segment continuous intramedullary T2-hyperintense signal intensity extending from D1 to conus [Figure 2]. Contrast-enhanced MRI of the brain revealed multiple tuberculomas diffusely distributed in brain parenchyma. IV methyl prednisolone 1 g/day was given for 3 days followed by oral prednisolone at a dose of 1 mg/kg/day. ATT (HRZE) was continued. Patient started showing signs of improvement 6 weeks after the therapy. Power in the bilateral lower limbs improved to MRC grade 3/5. Her neurological conditions improved gradually over 8-10 weeks. Now, after 1 year of follow-up, the patient has recovered completely without any residual neurological deficit.
|Figure 2: MRI spine showing continuous intramedullary T2 hyperintensity extending from D1 to conus|
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A 40-year-old male presented with low-grade fever for 2 weeks and acute-onset paraparesis with retention of urine for 1 day. There was no history of trauma or no past history of TB. Patient was conscious and oriented. Vital signs and general physical examination of the patient were normal. Cranial nerve examination did not reveal any deficit. Powers in bilateral upper limbs and lower limbs were MRC grade 5/5 and 0/5, respectively. Plantar reflexes were extensor. Fundus examination was normal and there was no gibbus. Rest of the systemic examination was normal. Routine blood biochemistries were normal including the HIV serology. Chest X-ray was also normal. CSF examination revealed 20 cells/ml (50% lymphocytes), protein 200 mg/l, sugar 35 mg/dl (blood glucose 80 mg/dl), and ADA 10 IU/L. AFB stains were negative, but PCR for M. tuberculosis was positive in the CSF. MRI of the spine revealed altered medullary signal intensity involving the dorsal cord from D6 to D10 levels, appearing hypointense on T1W and hyperintense on T2W images [Figure 3]. An orbital and brain MRI revealed no abnormality. The patient was put on ATT (HRZE). Methyl prednisolone 1 g IV for 3 days followed by prednisolone 1 mg/kg/day was given orally. The patient's neurological signs gradually improved over 8-10 weeks. After a follow-up of 1½ years, the patient recovered completely without any residual neurological deficit.
A 45-year-old male was brought to the emergency department with a history of fever for the past 10 days, urinary retention, and inability to walk for the past 3 days. There was no history of back pain or root pain. There was no past history of TB and trauma. Vital signs and general physical examination were normal. There was no cranial nerve palsy. Powers in the upper limbs and lower limbs were MRC grade 4/5 and 0/5, respectively. His plantar reflexes were flexor. He was confused and did not cooperate for sensory examinations. Fundus examination was normal and there was no gibbus. His routine blood chemistries were normal. HIV serology was negative and a chest X-ray was also normal. CSF examination showed a high opening pressure. There were 140 cells/ml in the CSF (60% lymphocytes, 40% polymorphs). The CSF protein was 440 mg/dl and sugar was 40 mg/dl (blood glucose 82 mg/dl). The CSF ADA was 6 IU/L; AFB and TB-PCR were positive. MRI of the spine showed patchy ill-defined T2 hyperintensities in the dorsal cord from D2 to D9 levels. An orbital and brain MRI did not reveal any abnormality. The patient was put on ATT (HRZE). Methyl prednisolone 1g IV for 3 days was also given, which was followed by oral prednisolone at a dose of 1 mg/kg/day. The patient's neurological signs improved gradually over 12 weeks. After a follow-up of 1 year, the patient recovered completely without any residual neurological deficit.
In view of the MRI findings in all our cases, which were consistent with LETM, a thorough work-up was planned. CSF viral serology and oligoclonal bands were negative. Serum vitamin B12, folate, and angiotensin converting enzyme levels were normal. Aquaporin 4 (IgM NMO) antibodies, anti-nuclear antibodies (ANA), dsDNA, and anti Ro/La were also found to be negative.
[Table 1] summarizes the various laboratories and radiological findings of all the four patients.
| :: Discussion|| |
Among patients with spinal TB, 55% present with vertebral body involvement, 39% with intraspinal granulomatous lesions without bone involvement, and only 7% with intramedullary lesions.  Intramedullary lesions usually present in the form of radiculomyelitis, transverse myelitis, intraspinal granulomas, and thrombosis of anterior spinal artery. , Dastur and Wadia described four major mechanisms that lead to spinal cord involvement in TB:
- Edema of border zones of the cord probably secondary to venous impediment due to pressure associated with meningitis,
- Ischemic myelomalacia resulting from vasculitis or post-thrombotic occlusion of meningeal vessels,
- Infrequent infarction of the cord from vascular occlusion, and
- Formation of intramedullary tuberculomas with pericentral necrosis. 
M. tuberculosis is a very rare cause of transverse myelitis. An abnormal activation of the immune system against the spinal cord is thought to be the main etiologic mechanism.  In more than 80% of patients, tuberculous myelitis involves more than one spinal segment, most commonly affected areas being the thoracic and cervical region. , LETM is a term designating a transverse myelitis that extends three or more vertebral segments in length. These lesions, which may occasionally span the entire length of the spinal cord, are much rarer and associated with greater morbidity.  The most frequent cause of LETM is NMO. 
Associations between NMO and active pulmonary TB have been suggested by a number of case reports and series, the most likely mechanism being immune-mediated inflammatory demyelination of the optic nerves and spinal cord triggered by pulmonary infection with M. tuberculosis.  Open-label use of ATT was reported as beneficial in patients with NMO refractory to immunotherapy.  LETM can also occur in various other autoimmune and inflammatory diseases that involve the CNS, such as multiple sclerosis, systemic lupus erythematosus (SLE) or Sjögren syndrome, or in infectious diseases of the CNS, especially in association with HIV infection.  Our patients did not have any evidence of autoimmune disease; neither did they satisfy the Wingerchuk revised diagnostic criteria for definite NMO.  Tubercular etiology was suggested in our cases in view of positive TB-PCR in the CSF of all the four cases and the presence of tuberculomas on MRI brain in two cases of which one had milliary TB. Further, they showed a good clinical and radiological response to ATT.
PCR for M. tuberculosis in the CSF is a very specific test with a sensitivity that ranges from 56% to 90% and a specificity that ranges from 88% to 100%.  In our case series, we used the amplification sequence of maltose basic protein (MBP) 64 protein gene. This amplification sequence has the least false positivity of all the sequences used (10% according to Lee et al. At a cutoff value of 10 IU/L, the sensitivity and specificity of CSF ADA were 82.14% and 90.91%, respectively.  MRI has been considered as the investigation of choice for diagnosis of LETM. The first documented description of using MRI to determine intramedullary spinal TB was published by Rhoton et al. in 1988. Lesions are usually hypointense on T1W images and iso-to hyperintense on T2W images with cord expansion.  Ramdurg et al. reported the largest series of 15 spinal intramedullary TB cases with varied MR changes.  The MRI findings in patients with intraspinal TB have both diagnostic and prognostic significance; cord atrophy or cavitation and the presence of syrinx are generally associated with poor outcome.  Our patients did not show any of these features on MRI and, hence, they all showed favorable outcomes. Since the neurologic deficits are mainly secondary to the inflammatory process, these lesions usually respond to medical therapy alone, and with early diagnosis, one can avoid unnecessary surgical intervention. Adjunctive corticosteroid has shown favorable outcomes in our cases and were advocated without evidence. While they worked in our series, their routine use cannot be generalized. Our cases highlight the fact that mycobacterial infections might be more common than usually suspected in myelitis. In endemic areas, particularly in patients with HIV infection, TB should be considered as an important etiologic factor in the differential diagnoses of LETM.
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[Figure 1], [Figure 2], [Figure 3]
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