Mædica - a Journal of Clinical Medicine

CASE REPORTS

245Maedica A Journal of Clinical Medicine, Volume 11 No.3 2016

MAEDICA – a Journal of Clinical Medicine2016; 11(3):245-249

An Uncommon Cause of

Longitudinally Extensive

Transverse Myelitis Catalina COCLITUa, Athena MERGEANIa, Teodora PARVUa, Octaviana RUSUa, Andrei CIOBOTARUa, Ovidiu BAJENARUa,b, Florina ANTOCHIa

a Neurology Department, University Emergency Hospital, Bucharest, Romaniab “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Address for correspondence:Dr. Catalina Coclitu, SUUB - Neurology, RomaniaEmail: catalina.coclitu@yahoo.com

Article received on the 29rd of July 2016. Article accepted on the 09rd of September 2016.

ABSTRACT

Considering that currently Romania has the highest tuberculosis incidence in Europe, the recognition of the infection is an acknowledged health issue. Central nervous system tuberculosis accounts for ap-proximately 1% of all cases of tuberculosis. Longitudinally extensive transverse myelitis is a contiguous infl ammatory lesion of the spinal cord which involves three or more spinal segments. In tuberculosis, spinal cord involvement is rare and is usually rather due to radiculomyelitis or spinal tuberculoma, and only very rare due to longitudinally extensive transverse myelitis.

We present the case of a 52-year-old man referred to our department for progressive neurological defi -cits due to a longitudinally extensive transverse myelitis. A# er a thorough work-up we diagnosed the patient with longitudinally extensive transverse myelitis secondary to infection with Mycobacterium tuberculosis.

Keywords: Central nervous system tuberculosis, longitudinally extensive transverse myelitis

BACKGROUND

Longitudinally extensive transverse my-elitis is defined as a contiguous, usually inflammatory lesion that involves three or more spinal segments.

In currently developing countries, such as Romania, tuberculosis is still a very im-portant health issue. In a report published in 2014, World Health Organization (WHO) esti-mated that there approximately 20 000 of new cases of tuberculosis registered every year in Romania, making the country the first one at

TB incidence among countries from the Euro-pean Economic Area (EEA) and European Union (EU) (1).

Of all cases of tuberculosis, central nervous system is affected in approximately 1%, with spinal cord involvement seen in less than half of these cases, with a higher prevalence for HIV infected individuals (2). Most often, central nervous system tuberculosis pertains to tuber-culous meningitis (95%), space-occupying ce-rebral or medular tuberculoma, and radiculo-myelitis, and very rarely to longitudinally extensive transverse myelitis (LETM) (3). q

AN UNCOMMON CAUSE OF LONGITUDINALLY EXTENSIVE TRANSVERSE MYELITIS

246 Maedica

A Journal of Clinical Medicine, Volume 11 No.3 2016

CASE REPORT

A 52-year-old man, chronic smoker with 32 pack-years of exposure, with a history of

alcohol consumption and with a nephew re-cently diagnosed with tuberculosis was referred to our department for a history of lower limbs ascending paresthesias, shortly followed by uri-nary retention and muscle weakness 5 days prior to admission. On admission the patient was febrile (37.6 ° C) without any other general signs. Muscle power was of 1/5 MRC (medical research council) in both lower limbs and 4/5 MRC in right upper limb. Deep tendon reflexes were brisk in the upper limbs, normal in right lower limb and absent in left lower limb, with no plantar response in right lower limb and a flexor response in left lower limb. All sensation modalities (pain, touch, temperature, joint po-sition and vibration) were impaired below tho-racic 8 (T8) spinal level. He also presented with urinary retention. No other additional sign was noted.

Routine blood tests were normal except for liver enzymes which were elevated (GOT 269 U/l, GPT 443U/l) and for a mild hyponatremia (Na 133 mmol/l). Serum vitamin B12 levels were also normal. HIV serology was negative and a chest X-ray was interpreted as normal.

We performed a cerebral MRI which proved normal, but the cervical and thoracic spine MRI showed a contiguous long lesion, extend-ing from cervical vertebral level C2 to thoracic

vertebral level T2, which was isointense on T1 and hyperintense on T2-weighted images, without contrast enhancement. Also, the MRI showed a certain extent of cervical vertebral degeneration (C4-C7).

FIGURE 1. Chest X-ray postero-anterior view- no obvious evidence of tuberculosis

FIGURE 2. T2-weighted sagi! al cervical and thoracic spinal cord MRI showing a long intramedullary hyperintense lesion without contrast enhancement

FIGURE 3. T2-weighted MRI showing a hyperintense lesion that extends from C2 to T2 spinal segments.

AN UNCOMMON CAUSE OF LONGITUDINALLY EXTENSIVE TRANSVERSE MYELITIS

247Maedica A Journal of Clinical Medicine, Volume 11 No.3 2016

Considering the findings we performed a lumbar puncture. The cerebral spinal fluid analysis showed 39 white blood cells count/mm3 with 15.4% lymphocytes and 84.6% neutrophils, elevated proteins (95 mg/dl), and a CSF glucose of 57 mg/dl (blood glucose 154 mg/dl), with normal opening pressure. Ziehl-Nielssen stains were negative, as well as the Gram stains.

The clinical and MR findings were consis-tent with longitudinally extensive transverse myelitis, so a thorough work-up was performed for possible causes of LETM, testing for a series of markers of autoimmune disorders. ANA, DNA-ds as well as CSF angiotensin converting enzyme were found to be negative. Consider-ing the patient’s history (his nephew was re-cently diagnosed with tuberculosis) and the re-sults from the lumbar puncture, we had a polymerase chain reaction (PCR) for Mycobac-terium tuberculosis from the CSF which also turned out negative. In order to rule out Neu-romyelitis optica (frequently associated with LETM) and multiple sclerosis (associated with transverse myelitis) we tested our patient for Anti-AQP4 antibodies, and for oligoclonal bands respectively, both being negative.

Paraneoplastic disease might also be re-sponsible for LETM, so we tested the patient for

onconeural antibodies which also proved to be negative.

Considering that even if all the tests for tu-berculosis were negative but the patient have been exposed to Mycobacterium tuberculosis and lacking an obvious cause for LETM we per-formed a CT scan of the lungs which showed a pulmonary nodule in the lower right lobe and a smaller one in the superior right lobe. We re-ferred the patient for a thoracic surgery consult and a biopsy. The histopathologic analysis of the specimen eventually revealed an epitheli-oid granuloma with caseous necrosis in the center confirming the diagnosis of Mycobacte-rium tuberculosis infection.

Before making the final diagnosis and start-ing the appropriate treatment, the patient was started on iv dexamethasone, 16 mg daily and ciprofloxacin daily for urinary tract infection. He gradually improved with corticotherapy, the muscle power of both lower limbs being of 2/5 MRC.The patient was referred to a tuber-culosis specialized center and never returned for a follow-up. q

DISCUSSION

Mycobacterium tuberculosis is an acid fast pathogenic bacterium that primarily in-

volves the lungs giving rise to tuberculosis. In developed countries the incidence of tubercu-losis decreased in the past decades, but in countries with a lower standard of life, the dis-ease is still a very serious health problem, being one of the front rank causes of infection related mortality and morbidity (4). An important pro-spective epidemiological study performed in Canada between 1970 and 2001 showed that the chance of developing CNS tuberculosis was 1.0% among 82,764 tuberculosis cases (5). The meninges is the most frequent site of CNS allocation, but amid patients with spinal TB 7% have intramedullary lesions (6).

The etiologies for longitudinally extensive transverse myelitis are fairly broad, but classi-cally it is associated with inflammatory demy-elinating disorders of central nervous system, such as Neuromyelitis optica, but many other causes are known, a rare one of them being the Mycobacterium tuberculosis infection (7). LETM due to mycobacterium tuberculosis is very rare.

One of the most important information about spinal cord involvement in tuberculosis

FIGURE 4. T2- weighted axial MRI of cervical spine showing an intramedullary hyperintense lesion

FIGURE 5. CT scan of the lungs showing pulmonary nodules in the right lung

AN UNCOMMON CAUSE OF LONGITUDINALLY EXTENSIVE TRANSVERSE MYELITIS

248 Maedica

A Journal of Clinical Medicine, Volume 11 No.3 2016

comes from an article published by Gupta back in 1994, which describes the lesions of my-elopathy as being usually hypointense in T1-weighted images, rarely as isointense, with iso-, hypo- or hyperintense lesions on T2 weighted images, with or without gadolinium enhance-ment according to the type of lesion they iden-tified (11 of there 20 patients had leptomenin-gitis and intramedullary lesions, 5 of them only intramedullary lesions, 2 leptomeningitis le-sions and 2 of them only extradural tuberculo-sis) (8). Considering this MRI findings we reck-oned with the diagnosis of possible tuberculous LETM, even if our patient didn’t have any past medical history of any kind of immunosuppres-sion to which spinal cord involvement is more related to in patients with tuberculosis (9). In case reports described in literature it seems that in more than 80% of tuberculous myelitis the most afflicted regions are the thoracic and cer-vical ones (10).

Back in 1969, in an extensive report, Dastur and Wadia described in India the most impor-tant mechanisms by which M. Tuberculosis in-fection leads to spinal cord involvement: ede-ma of the spinal cord vascular border zone probably as a result of venous high pressure due to meningitis, myelomalacia secondary to ischemia from the oclussion of the meningeal vessels, even spinal cord infarct because of vas-cular occlusion and the classical form of case-ous intramedullary tubeculomas (11).

Whereas our patients’ CSF PCR for myco-bacterium tuberculosis came negative and that PCR is a very specific test for M. Tuberculosis (with sensitivity that varies from 56% to 90%

and a specificity from 88% to 100%) we con-sidered that the mechanism leading to menin-gitis wasn’t due to meningitis per se, but rather to due to an immune-mediated inflammatory lesion of the spinal cord because of infectious cross-reactivity (12). The CT of the thorax raised the suspicion for this etiology and con-firmed the diagnosis. Nevertheless, in 2011 it was published a study that described the asso-ciation between NMO (with longitudinally ex-tensive transverse myelitis) and pulmonary tu-berculosis, citing an immune-mediate inflammatory mechanism as responsible for myelitis (13). NMO diagnosis criteria were re-visited in 2015, defining Anti-AQ4 seronega-tive NMO and NMO spectrum disorder which we considered that might also be a possible diagnosis. q

CONCLUSION

Tuberculosis is an important health issue worldwide, especially in countries currently

developing. While CNS tuberculosis accounts for only 1% of all cases of tuberculosis, it carries a great burden because of its high morbidity and mortality, and also because it is difficult to recognize. LETM is a rare but remarkable pre-sentation of Mycobacterium tuberculosis infec-tion that should be acknowledged by clinicians. Approaching the diagnosis as fast as possible has an important impact on the prognosis of the disease, especially in terms of disability. q

Conflict of interests: none declared.Financial support: none declared.

R!"!#!$%!&1. World Health Organization Regional

offi ce for Europe. Review of the national tuberculosis programme in Romania. 2014.

2. Rock RB, Olin M, Baker CA, Molitor TW, Peterson PK. Central nervous system tuberculosis: pathogenesis and clinical aspects. Clinical microbiology reviews. 2008;21:243-61

3. Jain RS, Kumar S, Tejwani S. A rare association of tuberculous longitudinally extensive transverse myelitis (LETM)

with brain tuberculoma. SpringerPlus. 2015;4.

4. Be NA, Kim KS, Bishai WR, Jain SK. Pathogenesis of central nervous system tuberculosis. Current molecular medicine. 2009;9:94-9.

5. Phypers M, Harris T, Power C. CNS tuberculosis: a longitudinal analysis of epidemiological and clinical features. The international journal of tuberculosis and lung disease : the offi cial journal of the International Union against

Tuberculosis and Lung Disease. 2006;10:99-103.

6. Muthukumar N, Venkatesh G, Senthilbabu S, Rajbaskar R. Surgery for intramedullary tuberculoma of the spinal cord: report of 2 cases. Surgical neurology. 2006;66:69-74.

7. Bhargava P, Elble RJ. Clinical Reason-ing: an unusual cause of transverse myelitis? Neurology. 2014;82:e46-50.

8. Gupta RK, Gupta S, Kumar S, et al. MRI in intraspinal tuberculosis.

AN UNCOMMON CAUSE OF LONGITUDINALLY EXTENSIVE TRANSVERSE MYELITIS

249Maedica A Journal of Clinical Medicine, Volume 11 No.3 2016

Neuroradiology. 1994;36:39-43.9. Hernandez-Albujar S, Arribas JR, Royo

A, et al. Tuberculous radiculomyelitis complicating tuberculous meningitis: case report and review. Clinical infectious diseases : an offi cial publication of the Infectious Diseases Society of America. 2000;30:915-21.

10. Wasay M, Arif H, Khealani B, Ahsan H. Neuroimaging of tuberculous myelitis:

analysis of ten cases and review of literature. Journal of neuroimaging : offi cial journal of the American Society of Neuroimaging. 2006;16:197-205.

11. Dastur D, Wadia NH. Spinal meningiti-des with radiculo-myelopathy. 2. Pathology and pathogenesis. Journal of the neurological sciences. 1969;8:261-97.

12. Liu PY, Shi ZY, Lau YJ, Hu BS. Rapid diagnosis of tuberculous meningitis by a

simplifi ed nested amplifi cation protocol. Neurology. 1994;44:1161-4.

13. Zatjirua V, Butler J, Carr J, Henning F. Neuromyelitis optica and pulmonary tuberculosis: a case-control study. The international journal of tuberculosis and lung disease : the offi cial journal of the International Union against Tuberculosis and Lung Disease. 2011;15:1675-80.