Paradoxically developed optochiasmatic tuberculoma and tuberculous lymphadenitis: a case report with 18-month follow up by MRI.

Abstract: We report the first case of extracranial tuberculous lymphadenitis which paradoxically developed during treatment of intracranial tuberculoma. Our patient, a 15-year-old girl who initially presented with meningitis and intracranial tuberculomas, developed extracranial tuberculomas during treatment for central nervous system tuberculosis. She was followed clinically with cerebrospinal fluid (CSF) studies and magnetic resonance imaging (MRI) at three monthly intervals. Within 18 months of specific antituberculous treatment, the patient had fully recovered. The course and response to therapy are discussed in light of the current literature.

Key Words: tuberculous lymphadenitis, extracranial, intracranial optochiasmatic tuberculoma

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Central nervous system (CNS) tuberculosis (TB), a relatively common manifestation of TB in developing countries, is experiencing a recent surge in the developed world. CNS tuberculosis may appear in diffuse or localized forms, including tuberculoma, abscess or cerebritis. (1) Tuberculous meningitis and intracranial (IC) tuberculomas are the two most frequent manifestations of CNS tuberculosis. (1,2) IC tuberculomas with paradoxical response to antituberculous chemotherapy have been documented worldwide. In all of these reported cases, tuberculomas developed or enlarged during proper antituberculous treatment of patients with intra- and extracranial TB. (3) Although rare, optochiasmatic involvement represents another form of IC tuberculomas. Prognosis is poor, especially when diagnosis is delayed and treatment is not adequate. (4)

Our patient, who initially presented with meningitis and IC tuberculomas, paradoxically developed a cervical tuberculous lymphadenitis and multiple IC tuberculomas. To our best knowledge, there is no report in the English literature of paradoxically developed extracranial tuberculomas during treatment of CNS tuberculosis, and due to its interesting nature, we present this unusual case. Relevant literature is reviewed and the diagnosis, treatment and course are discussed.

Case Report

A 15-year-old girl was admitted to our clinic with impaired consciousness, agitation, headache and vomiting. Her history revealed that she had a sudden onset of headache and vomiting a week before admission. Three days after manifestation of symptoms she was seen by a physician and given an analgesic, a vitamin and some type of antibiotic. During the following 2 days (5th day of the complaints) she had a fever of 37.7[degrees]C. Due to worsening of the headache and loss of consciousness, she was admitted to our clinic. Her family history revealed that three years previously, her father had lung tuberculosis and had received treatment for one year.

Physical examination revealed a bad general condition, somnolence, and an axillary fever of 37.4[degrees]C. She had medial deviation in both eyes, neck stiffness, positive Kernig and Brudzinski signs, and bilateral positive Babinski signs. Laboratory findings revealed WBC of 9,400/[mm.sup.3], erythrocyte sedimentation rate of 19 mm/h, and a C-reactive protein of 16 U/L. Cerebrospinal fluid (CSF) and initial cranial MRI findings are listed in the Table. Ziehl-Neelsen staining of CSF for acid-fast bacilli (AFB) was positive. Cerebrospinal fluid (CSF) culture on Lowenstein Jensen (LJ) medium yielded Mycobacterium tuberculosis at the 40th day. Chest x-ray and ultrasound of the abdomen revealed no abnormality. A combined antituberculous drug therapy was started with rifampin, isoniazid, streptomycin and pyrazinamide. The patient was also given 32 mg/d of dexamethasone. She became conscious on the second day of treatment and her body temperature returned to normal. She was diagnosed with restriction of lateral movement of both eyes and diplopia. Ophthalmological examination revealed bilateral abducens paresis and optic disc edema in the left eye. On the 15th day of antituberculous chemotherapy, she was conscious and had no neurologic deficit other than the abducens paresis. Dexamethasone was tapered beginning at day 15 and was discontinued at day 30 of treatment. Three days after the tapering dose of dexamethasone was begun, on the 18th day of treatment, she began to have intermittent subfebrile fever.

During the first month of therapy, cranial MRI revealed an increase in the size of the tuberculoma and new tuberculomas, and optochiasmatic tuberculoma also appeared. Repeated cranial MRI and CSF findings are given in the Table. Eye examination revealed the continuation of bilateral abducens paresis and left optic disc edema. Side vision examination revealed normal findings on the right and enlargement of the blind spot on the left (consistent with the disc edema). The CSF smear for M tuberculosis was positive. The M tuberculosis species isolated from the first culture was determined to be sensitive to first line antituberculous drugs. The treatment was continued without any modification. The patient continued to have intermittent subfebrile fever until the 60th day of the treatment. By the 70th day of treatment, she was discharged following resolution of fever X 10 days.

By the third month of therapy, the patient noticed a swelling on the right side of the neck and was readmitted to our clinic. A 3 X 2 cm single lymph node was found in the right posterior cervical chain. Fine needle biopsy revealed acid-fast bacilli (AFB). The patient was screened radiologically following determination of extracranial involvement. Cranial MRI and CSF examination results are given in the Table. Chest x-ray and ultrasound of the abdomen were both normal. Cervical MRI revealed tuberculomas in the craniocervical junction anterior to the bulbus and cerebellar tonsils. Thoracolumbar MRI findings were normal. CSF smear revealed no AFB or M tuberculosis. The patient was followed with successive cranial MRI and CSF examinations. The findings are summarized in the Table.

During the sixth month of therapy, an approximate 4 X 5 cm fluctuating, conglomerated lymph node was detected in the right posterior cervical chain. The restriction of lateral eye movement disappeared. A minimal optical blind spot was detected on the temporal site of the left optic disc. Visual field examination was normal. Microscopy and culture for M tuberculosis of the CSF was negative.

During the 9th month of the therapy, the cervical MRI revealed complete disappearance of the lesion. The patient was without complaints. Physical examination revealed reduction in the size of the cervical lymph node, down to 0.5 X 0.5 cm, (with final disappearance by the 10th month of the treatment). Ocular examination revealed a minimal temporal sequelae on left optic disc. The right eye was normal.

At the 12th month of the therapy, the CSF findings were normal. Physical examination revealed complete resolution of the cervical lymph node, with residual scar tissue. Routine laboratory findings were within normal ranges.

By the 15th month of the therapy, the patient remained without complaints, and cranial MRI findings revealed only a 2 to 3 mm noncontrasting hypointense area in the left cerebellum (See Table). By the 18th month of the therapy, the cranial MRI findings were normal, and antituberculous therapy was discontinued. The patient was followed for 10 more months and no relapse was observed.

Discussion

Central nervous tuberculosis involves the meninges and/or parenchyma. Parenchymal disease may occur with or without coexistent meningitis, as was seen in our patient. We present here an interesting case of an optochiasmatic tuberculoma and extracranial cervical lymphadenopathy which paradoxically developed during antituberculous drug therapy for CNS TB. The patient had no history of tuberculosis or any head injury, was HIV negative and had no obvious impact of immunocompromization. No concurrent extracranial lesions were detected at admission. A cervical lymphadenitis was diagnosed 3 months after the diagnosis of CNS tuberculosis, while the patient was undergoing four-drug antituberculous therapy.

The coexistence of extraneural tuberculosis is not rare in cases of CNS tuberculosis, (1,5) and this may provide a clue to the diagnosis of CNS TB whenever observed. Yet, in IC TB, cases of intraspinal involvement may also be present (1) necessitating the expansion of neuroimaging procedures to include both the brain and spine. In our patient, however, there was no coexistence of extracranial involvement with the CNS tuberculosis at the time of admission. In addition, further radiological assessments were performed when we discovered a paradoxical increase of the number and size of tuberculomas during chemotherapy, but no intraspinal involvement was noted.

It is well known that paradoxical development of tuberculomas during drug therapy does not usually represent failure or resistance of antituberculous therapy. (3,6) The development of TB meningitis or IC tuberculomas during therapy for intra and extra-CNS tuberculosis has been well documented. (3,6,7) The important features in our patient are the development of IC tuberculomas (including optochiasmatic involvement) and cervical tuberculous lymphadenitis (extra-CNS tuberculosis) during effective treatment of CNS tuberculosis, as indicated by susceptibility of the isolated pathogen to the medication. To our knowledge, this represents the first case of this unusual course of CNS tuberculosis.

Optochiasmatic tuberculomas are very important and if an early diagnosis and adequate treatment is not implemented, (4) an insidious onset and progressive visual loss may occur. (4,8) In our case, no visual loss was present and the outcome was favorable with antituberculous therapy and corticosteroids. This may be due to the perichiasmatic nature of the tuberculoma; however, since the MRI can not differentiate between the intra- and perichiasmatic histologic types, it could not be concluded. (9-11)

Due to the variable nature of response to medical therapy, and the persistent and even paradoxical development of meningeal and parenchymal lesions despite adequate treatment, (1) we employed long-term follow-up, judging the activity of tuberculoma according to the degree of contrast enhancement in the MRI after CSF findings returned to normal. (1) We observed that normalization of CSF findings was followed by the disappearance of dural contrast enhancement and finally, complete resolution of tuberculomas, irrespective of their appearance. In our case, marked clinical improvement, as reflected by improvement of ophthalmic symptoms and lymphadenitis and the complete disappearance of the IC and optochiasmatic tuberculomas, was achieved by utilization of the four-drug antituberculous therapy (streptomycin X 1 month, pyrazinamide X 2 months. Isoniazid and rifampin X 18 months). We achieved a good result with this regimen, compared with previous reports which suggest a prolonged treatment for up to 30 months in cases showing paradoxical expansion. (5,12) Our patient continued to do well 10 months following therapy.

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In conclusion, the present case indicates three important points: First, to our knowledge, this is the first case of cervical lymphadenitis to develop paradoxically during antituberculous drug therapy for CNS TB. Second, a good clinical improvement was observed with relatively short term antituberculous therapy compared with the suggested prolonged therapy. Third, the activity of tuberculomas was detectable by MRI until 3 to 6 months after the normalization of CSF findings.

References

1. Bernaerts A, Vanhoenacker FM, Parizel PM, et al. Tuberculosis of the central nervous system: overview of neuroradiological findings. Eur-Radiol 2003;13:1876-1890.

2. Jain VK, Chandramukhi A, Venkataramana NK, et al. The far cry of TB brain: report of a case of tubercular meningitis, multiple tuberculomas and tubercular abscess. Clin Neurol Neurosurg 1989;91:171-176.

3. Hejazi N, Hassler W. Multiple intracranial tuberculomas with atypical response to tuberculostatic chemotherapy: literature review and a case report. Infection 1997;25:233-239.

4. Akhaddar A, El Hassani MY, Chakir N, et al. Optochiasmatic tuberculoma: complication of tuberculous meningitis: report of a case and review of the literature. J Neuroradiol 2001;28:137-142.

5. Wasay M, Moolani MK, Zaheer J, et al. Prognostic indicators in patients with intracranial tuberculoma: a review of 102 cases. J Pak Med Assoc 2004;54:83-87.

6. Afghani B, Lieberman JM. Paradoxical enlargement or development of intracranial tuberculomas during therapy: case report and review. Clin Infect Dis 1994;19:1092-1099.

7. Teoh R, Humphries MJ, O'Mahony G. Symptomatic intracranial tuberculoma developing during treatment of tuberculosis: a report of 10 patients and a review of the literature. Q J Med 1987;63:449-460.

8. Sharma K, Pradhan S, Varma A, et al. Irreversible blindness due to multiple tuberculomas in the suprasellar cistern. J Neuro-Ophthalmol 2003;23:211-212.

9. Clavier E, Thiebot J, Freger P, et al. Optochiasmatic tuberculoma and MRI: 2 cases. J Radiol 1988;69:333-337.

10. Beneggi A, Adamoli P, Bernardini E, et al. Tuberculous meningitis: a case with severe ocular complications. Pediatr Med Chir 1995;17:465-469.

11. Gotoh K, Nishiura I, Nagata N, et al. Multiple cerebral tuberculomas presenting with paradoxical expansion: a case report. No Shinkei Geka 2001;29:1075-1079.

All art is autobiographical. The pearl is the oyster's autobiography.
--Federico Fellini

Ahmet Kalkan, MD, Selami Serhatlioglu, MD, Mehmet Ozden, MD, Affan Denk, MD, Kutbettin Demirdag, MD, Turgut Yilmaz, MD, and Suleyman Sirri Kilic, MD

From the Departments of Infectious Diseases, Radiology, Immunology and Ophthalmology, Firat University Medical School, Elazig, TR23119 Turkey.

Reprint requests to Ahmet Kalkan, MD, Department of Infectious Diseases, Firat University, Medical School, Elazig, Turkey. Email: [e-mail]

Accepted January 4, 2006.

RELATED ARTICLE: Key Points

* This report presents, for the first time, a case of extracranial tuberculous lymphadenitis which paradoxically developed during treatment of intracranial tuberculoma.

* The case was followed up by clinical appearance and magnetic resonance imaging at three monthly intervals.

* Within 18 months of specific antituberculous treatment, she was fully recovered.

Table. Serial cerebrospinal fluid (CSF) and MRI findings of the case

Follow up                                MRI findings
(months)   CSF findings                  Meningeal enhancement

Initial    Appearance of fluid:          A pattern of minimal contrast
           Xantochromic Cell               in the dura
           (/[mm.sup.3]): 140 (35% PNL,
           65% lymphocyte)
           Protein (mg/dL): 85
           Glucose (mg/dL): 35
 1         Appearance of fluid:          A pattern of prominent
           Xantochromic Cell               contrast in the dura
           (/[mm.sup.3]): 970 (35% PNL,
           65% lymphocyte)
           Protein (mg/dL): 125
           Glucose (mg/dL): 129
 3         Appearance of fluid: Clear    The meningeal involvement
           Cell (/[mm.sup.3]): 90 (5%      disappeared
           PNL, 95% lymphocyte)
           Protein (mg/dL): 187
           Glucose (mg/dL): 60
 6         Appearance of fluid: Clear    No meningeal involvement
           Cell (/[mm.sup.3]): 50 (100%
           lymphocyte)
           Protein (mg/dL): 164
           Glucose (mg/dL): 39
 9         Appearance of fluid:          No meningeal involvement
           ClearCell (/[mm.sup.3]): 40
           (100% lymphocyte)
           Protein (mg/dL): 150
           Glucose (mg/dL): 55
12         Normal CSF findings           No meningeal involvement
15                                       No meningeal involvement.

                                  MRI findings
Follow up  Changes in number and size of
(months)   tuberculomas                    Optochias matic involvement

Initial    A couple of millimetric sized   No optochiasmatic involvement
             tuberculomas, localized in
             the left temporo-occipital
             side and right
             frontotemporal side.
 1         An increase in the size of      A 5 mm optochiasmatic
             tuberculoma on the left         tuberculoma, localized
             lateral vertex and a new        towards to the left optic
             tuberculoma in the right        nerve
             cerebellar pontine area.
 3         Lower number of granulomas      Similar to the previous scan
             which were also smaller in      (at 1st month)
             size (the largest being
             about 10 x 15 mm)
 6         Similar to the previous scan    The lesions around the optic
             (at 3 months of therapy)        chiasm became more
                                             prominent
 9         A slight decrease in the sizes  Decrease in the dimensions of
             (the largest being about        the optochiasmatic
             10 X 10 mm) of the observed     tuberculoma
             tuberculomas compared to
             previous.
12         Similar to the previous scan    Similar to the previous scan
             (at 9th month of therapy)       (at 9th month of therapy)
15         Normal cranial MRI findings,    The lesion on the level of
             except for a 2-3 mm             optic chiasm disappeared.
             noncontrast hypointense area
             in the left cerebellum.

1, at first month of therapy; 3, at 3rd month of therapy; 6, at 6th
month of therapy; 9, at 9th month of therapy; 12, at 12th month of
therapy; 15, at 15th month of therapy; PNL, polymorphonuclear
lymphocytes.