| Abstract|| |
Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis is an infectious disease that continues to be a significant health problem in a developing country like India. The cause of peripheral neuropathy associated with tuberculosis is controversial. Possibilities include the toxic effects of anti-tuberculous chemotherapy (especially, rifampicin, streptomycin & ethambutol), immune mediated neuropathy, direct invasion of nerves, vasculitic neuropathy, compressive neuropathy, and meningitic reaction. This report describes an unusual finding of tuberculous granulomas in the peripheral nerve (Greater auricular nerve) of a patient ,who presented with a painful neck swelling. Granulomas were present in Greater auricular nerve (C2,C3) biopsy specimen associated with tuberculous peri-neuritis, but with no more specific indications of the mechanism of the neuropathy.
Keywords: Anti-tubercular chemotherapy, granuloma, greater auricular nerve, peri-neuritis, peripheral nerves, tuberculoma, tuberculosis, tuberculous neuritis
|How to cite this article:|
Warpe BM, Poflee SV, Pande NP, Shrikhande AV. Tuberculous neuritis: A rare sequel of a common disease. Indian J Pathol Microbiol 2014;57:69-71
| Introduction|| |
The causative association of peripheral neuropathy with tuberculous infection is controversial. Many possibilities have been studied, with no definite single cause.  This report describes the rare finding of the presence of tuberculous granulomas in cervical lymph nodes associated with tuberculous involvement of the adjacent peripheral nerve - the greater auricular nerve (C2,C3) - on microscopic examination in a patient who had presented with a painful neck swelling.
Cervical lymph nodes were probably involved initially by tuberculosis, and the tuberculous infection affected the peripheral nerve later on. Neuropathy preceded the anti-tubercular drug treatment.
Neuropathy in patients with tuberculosis is not always iatrogenic and the possibility of a primary effect on the nerves should be considered. A high degree of suspicion in cases of tuberculosis with unusual presentation, early diagnosis and timely anti-tubercular treatment can avoid complications such as neuropathy.
| Case Report|| |
A 69-year-old female presented with left-sided neck swelling since 13 months and pain over the swelling since 1 week. She also complained of progressive weight loss for the last 6 months. There was no present or past history of fever or cough. On examination, a single 9 cm × 2 cm × 1 cm firm, tender, tubular swelling was noted over the left side of the neck. The patient did not have other swellings or disease stigmata.
X-ray of the chest and neck were normal. Neck ultrasonography was reported as suspicious of thrombosed retro-mandibular vein and non-contrast computerized tomography (CT) neck was indicative of thrombosis of the left external jugular vein. CT chest revealed no specific finding like lung consolidation, pleural effusion or malignancy. Ultrasonography and CT abdomen performed for presence of lymphadenopathy or any other mass lesion revealed mild hepatomegaly with no evidence of primary malignancy.
The erythrocyte sedimentation rate (ESR) of the patient was 40 mm at the end of the first hour by the Wintrobe method. The patient was non-reactive for HIV I and II.
Because of the clinical suspicion of a vascular lesion of the neck, fine needle aspiration cytology study of the swelling was not performed. On the basis of clinical and radiological findings, the patient was operated under general anesthesia.
The excised mass from the left side of the neck [Figure 1] was sent for histopathological study. On gross examination, the specimen consisted of a single cord-like tubular tissue of size 9 cm × 2 cm × 0.5 cm, with an irregular mass adhered to its center with minute yellowish, 2-3-mm-sized tiny nodules on the external surface [Figure 2].
|Figure 1: The dissected cord-like structure with minute 2-3 mm nodules on the external surface|
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|Figure 2: The resected cord-like, tubular, white structure with attached irregular mass at the center of the lesion|
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On hematoxylin and eosin staining, tissue sections from the irregular mass revealed multiple small lymph nodes completely replaced by classical caseating granulomas of tuberculosis [Figure 3]. In addition, sections from the cord-like structure showed caseating granulomas comprising of epitheloid cells, Langhans giant cells and lymphocytes in the nerve fascicles with disruption of the perineurium and surrounded by granulomatous reaction in the adjacent lymphoid and fibrofatty tissue [Figure 4]. No foamy macrophages (Lepra cells) were seen. The impression conveyed was of tuberculous lymphadenitis with periadenitis. Follow-up and investigations for tuberculosis were advised.
|Figure 3: Multiple lymph nodes showing caseating granulomas (hematoxylin and eosin [H&E], ×100), arrow and inset (H&E, ×400) showing Langhans giant cell|
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|Figure 4: Caseating granulomas in the nerve fascicles and surrounding lymphoid tissue (hematoxylin and eosin [H&E], ×100), thin arrow-perineurium, thick arrow-uninvolved nerve fascicle. Inset (H&E, 400)-granuloma with Langhans giant cell inside the nerve substance|
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On review of the slides, caseating granulomas were identified in the lymph nodes, nerve substance and the surrounding tissue. Special stains for acid fast bacilli performed on the lymph node and the nerve were negative. With characteristic microscopic features, the final impression given was tuberculous lymphadenitis with perineuritis and nerve granuloma.
Ziehl Nelson staining for acid fast bacilli on the patient's sputum sample was negative. Tuberculosis specialists started the patient on anti-tubercular drugs based on the histopathological report and their clinical suspicion.
During follow-up at 3 months, local examination revealed no pain or residual swelling in the neck and the patient was responding well to anti-tubercular medication. On follow-up at 6 months, the patient had no recurrent swelling and had regained the lost body weight with a sense of well being. However, she developed post-operative sensory deficit over the areas supplied by the great auricular nerve, i.e., the skin overlying the parotid gland, mastoid process and both surfaces of the outer ear.
| Discussion|| |
Lymphadenitis is the most frequent presentation of extra-pulmonary tuberculosis. Cervical lymph nodes are the most common lymph nodes to get involved and present as a neck mass.  However, cervical nerve involvement associated with cervical lymphadenitis is rarely quoted in the literature.
We have come across a patient in whom diagnosis was made on the basis of characteristic microscopic features of tuberculosis seen in the cervical lymph nodes and surrounding nerve tissue. Her increased ESR was the only other indicator of a chronic disease process. In the present case, cervical lymph nodes were probably involved initially by tuberculosis, although they were never palpable separately. Later on, tuberculous infection involved the adjacent great auricular nerve (peripheral nerve). The exact mechanism of neuropathy could not be ascertained in our patient. Possibilities include direct effects of the tuberculous exudates on the nerve and cytokine-mediated damage. 
Peripheral nerves can be directly affected by tuberculosis and neuropathy is attributable to peripheral nerve pressure and direct effects of the tuberculous exudates on the nerve.  Peripheral neuropathy is a unique and unusual presentation of tuberculosis and is attributed to compression by vertebral collapse or cold abscess according to Naha et al.  They have concluded that further studies are required to elucidate the mechanism of neurotoxicity in tuberculosis and identify the putative mediators. Nerve involvement secondary to regional tubercular lymphadenitis is reported by Goussard et al.  They have published a series of eight cases of phrenic nerve palsy in children caused by tuberculosis lymph gland infiltration of the phrenic nerve. According to them, nerve compression by inflammatory granulomatous tissue is responsible for neuropathy.
Peripheral polyneuropathy commonly occurs following exanthematous fevers and acute bacterial infections. The most common cause of neuropathy is leprosy and the primary process is axonal damage secondary to the inflammatory response.  In lepromatous leprosy, there is infiltration of the nerve by bacteria and inflammatory cells and fibroblastic proliferation causing fusiform enlargement of the nerves. In tuberculoid leprosy, nerve enlargement occurs as a result of acute neuritis. 
Neuropathy in patients with tuberculosis was attributed to alcohol and malnutrition, but more recently has been attributed to anti-tuberculosis medication and a radiculopathy as a result of tuberculous meningitis.  A vasculitic neuropathy has also been proposed but with no direct evidence of vasculitic abnormality in the nerve.  Mycobacterium avium-intracellulare has been implicated in neuropathy in patients with HIV. 
Tuberculous neuritis occurring after anti-tubercular medication has been studied, especially by isoniazid and ethambutol. , Isoniazid causes pyridoxine deficiency neuropathy that is initially sensory and later motor with features of axonal degeneration. Excess pyridoxine itself may cause a reversible sensory neuropathy. Ethambutol can produce a retrobulbar toxic neuropathy or reversible distal sensory peripheral neuropathy. Streptomycin is vestibulotoxic but does not cause peripheral neuropathy. 
The association of tuberculosis with Guillain-Barré syndrome is uncertain.  Peripheral neuropathy is a rare manifestation of sarcoidosis. Sarcoidosis and tuberculosis may occasionally coexist. 
In our patient, the neck swelling was brought to notice because of pain. If the patient had presented earlier, the nerve might not have been involved. However, there was no evidence of tuberculosis or other granulomatous infection elsewhere. The limitation of our study is that there was no pre-operative documented evidence of tuberculosis.
Tuberculosis is a disease with widespread body tissue involvement and shows many unusual modes of presentation. Good response to anti-tubercular treatment substantiates the diagnosis of tuberculosis in these cases. A high degree of suspicion on the part of specialists and tissue diagnosis before major surgical intervention becomes imperative in such unusual cases. Immunohistochemistry and ultrastructural studies may highlight the exact mechanism.
We have not come across a similar case of isolated cervical nerve involvement following regional tuberculous lymphadenitis in the literature. In our patient, the neuropathy preceded the anti-tubercular drug treatment. Neuropathy in patients with tuberculosis is not always iatrogenic and the possibility of a primary effect on the nerves should be considered.
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Bhushan M Warpe
Room No. 89, NRH, IGGMC, Nagpur - 440 018, Maharashtra
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4]