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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2016  |  Volume : 27  |  Issue : 1  |  Page : 135-138
Multiple intracranial tuberculomas in a post-kidney transplant patient


1 Infectious Disease and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Infectious Disease and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Internal Medicine, Faculty of Medical Sciences, University of Duhok, Azadi Hospital Street, Dohuk, Kurdistan, Iraq

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Date of Web Publication15-Jan-2016
 

   Abstract 

Tuberculosis (TB) is a serious public health problem worldwide, particularly in developing countries. The most common presentation of TB is the pulmonary form; however, extrapulmonary manifestations are not uncommon, particularly in the immunocompromised patients. TB of the central nervous system is the most severe extrapulmonary presentation. We report a post-kidney transplant patient who had multiple ring-like lesions on contrast-enhanced magnetic resonance imaging (MRI). Based on the results of MRI and biopsy specimen, the patient was diagnosed with multiple intracranial tuberculomas. He was treated successfully with a standard quadruple therapy of rifampicin, isoniazid, ethambutol and pyrazinamide.

How to cite this article:
Yadegarynia D, Merza MA, Sali S, Seghatoleslami ZS. Multiple intracranial tuberculomas in a post-kidney transplant patient. Saudi J Kidney Dis Transpl 2016;27:135-8

How to cite this URL:
Yadegarynia D, Merza MA, Sali S, Seghatoleslami ZS. Multiple intracranial tuberculomas in a post-kidney transplant patient. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2019 Nov 14];27:135-8. Available from: http://www.sjkdt.org/text.asp?2016/27/1/135/174163

   Introduction Top


Tuberculosis (TB) is increasingly recognized as a serious public health problem worldwide, particularly in developing countries. [1] The most common presentation of TB is the pulmonary form; however, extrapulmonary manifestations are not uncommon, particularly in the immunocompromised patients. TB of the central nervous system (CNS) is the most severe extrapulmonary presentation, which may have forms of meningitis, tuberculoma or abscess formation. [2] Although the incidence of CNS TB has declined since the advent of effective anti-TB chemotherapy, it may still occur in approximately 1% of the cases. [3] There are reports of tuberculous meningoencephalitis in the literatures, [4] but documented cases of multiple intracranial tuberculomas in immunocompromised hosts are a rare presenting feature.

We report a post-kidney transplant patient who was diagnosed, based on the results of magnetic resonance imaging (MRI and biopsy specimen, to have multiple intracranial tuberculomas. He was treated successfully with a standard quadruple therapy of rifampicin, isoniazid, ethambutol and pyrazinamide.


   Case Report Top


A 54-year-old Iranian man with diabetic nephropathy received a living donor kidney transplant seven years earlier. His post-transplantation course was favorable for the first 6.5 years; however, it was complicated by two events of sickness during the past five months. With regard to past medical history, the patient had secondary hypertension secondary to endstage renal failure, and there was no family history of TB.

In the first episode, the patient presented to the emergency department in a tertiary care referral hospital with fever, malaise and confusion for six days. Physical examination was unremarkable, apart from mild fever. Laboratory investigations revealed leukopenia and increased serum creatinine. All other tests were normal, including computed tomography (CT) scan of the brain. He was treated with supportive care and mycophenolate mofetil (CellCept) medicine was stopped because of dropped white blood cell (WBC) count. He also received granulocyte-macrophage colonystimulating factor for correction of WBCs. His condition improved over 10 days and he was discharged home in a stable condition.

After 45 days, the patient was again admitted into the emergency department with fever, sweating, malaise and vomiting for one week. Thereafter, the patient developed dizziness, two attacks of seizure and gradual deterioration in the level of consciousness (LOC), with a Glasgow Coma Scale score of 12. Physical examination showed a temperature of 38°C, a pulse rate of 100 beats/min, a respiration rate of 16 breaths/min and a blood pressure of 130/80 mm Hg. The patient was mildly irritable; otherwise, there were no abnormalities on examination. There was no peripheral lymphadenopathy or hepatosplenomegaly.

Laboratory investigations included complete blood cell count: hemoglobin of 12.7 g/dL and WBC of 4.4 × 10 3 /μL, and the differential count of polymorphs, lymphocytes, monocyte and eosinophils was 83%, 13%, 3% and 1%, respectively, and the platelet count was 270 × 10 3 /μL. The erythrocyte sedimentation rate (ESR) was 32 mm/h and C-reactive protein was 41 mg/L. Urinalysis revealed glycosuria and proteinuria; Routine biochemical parameters were as follows: fasting blood sugar, 240 mg/dL; blood urea nitrogen, 87 mg/dL; Serum creatinine, 2.3 mg/dL; serum sodium, 132 mEq/L; serum potassium, 5 mEq/L; and alkaline phosphatase, bilirubin and hepatic transaminases were within normal limits. Serum and broncho-alveolar lavage for galactomannan were negative. Serial virology of human T-lymphotropic virus Ab (1 and 2), human immunodeficiency virus, hepatitis B virus and hepatitis C virus were negative. The toxoplasma antibody titers were negative for IgM but positive for IgG and a Venereal Disease Research Laboratory test was negative. Urine and blood cultures were negative. Molecular diagnostic tests of sputum for cytomegalovirus, BK virus, JC virus, herpes simplex virus, Pneumoncystis jiroveci and fungi were negative. The sputum was negative for acid fast bacilli (AFB) on three consecutive smear examinations. A polymerase chain reaction (PCR) analysis for Mycobacterium tuberculosis was reported to be negative. Interferongamma release assays (IGRA) were negative. Cerebrospinal (CSF) examination revealed a protein level of 152 mg/dL, decrease glucose (40 mg/dL) and polymophonuclear pleocytosis (80%). Chest X-ray (CXR) was normal. Transthoracic and trans-esophageal echocardiograms were normal. A smear microscopy of CSF for AFB was negative and, further, a PCR for M. tuberculosis complex was also negative. An MRI with and without contrast was advised. MRI without contrast demonstrated multi illdefined low-density masses involving the brain, whereas MRI with contrast showed diffuse and bilateral ring enhancement cerebral lesions [Figure 1]a and b. According to the above picture, the patient was started on broad-spectrum antibiotics and empirical antiTB drugs, while brain biopsy was planned for him. Biopsies of the left frontal lobe of brain and lepto-meninges revealed extensive tissue necrosis and non-specific inflammation and edema and mild non-specific inflammation, respectively. The same specimens were positive for AFB in smear microscopy and the culture result was positive for M. tuberculosis. Finally, based on the above evidence, a diagnosis of intracranial tuberculomas was made.
Figure 1: Contrast-enhanced (a) axial and (b) coronal magnetic resonance images showing diffuse and bilateral hypo-intense lesions in the white matter and subcortical area of the brain with ring-like enhancement.

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In the first three weeks following standard quadruple therapy of rifampicin (600 mg/ day), isoniazid (300 mg/day), ethambutol (500 mg/day), and pyrazinamide (1000 mg/day), the patient's neurological symptoms continued to progress and he developed right-side hemiparesis. Although the patient was on an initial dose of 20 mg prednisolone, the dose of corticosteroid was increased. However, later, the clinical response to therapy was successful and the patient's LOC responded markedly.


   Discussion Top


Multiple intracranial tuberculomas are an uncommon presenting feature of TB in immunocompromised patients. [5] The pathogenesis of intracranial tuberculoma includes deeply seeded small caseous foci in the brain during a recent or remote hematogenous spread of the TB bacilli. In our case, the cause of tuberculoma was claimed to be due to the latter as there was no apparent concurrent involvement of other organs. There was no evidence of pulmonary TB in our patient, although it has been shown that in 30-70% of cerebral tuberculoma there is evidence of active TB elsewhere in the body. Cerebral tuberculoma results usually from the rupture of the subependymal tuberculous foci into the subarachnoid space rather than from direct hematogenous seeding. [6] In our case, multiple tuberculomas might be related to the immunosuppressant status of the patient. It has been stated that a higher degree of immunosuppression might induce a greater number of tuberculomas in the CNS. [7]

In our case, the diagnostic clue features of fever, sweating, malaise, dizziness and seizure attacks had a wide range of differential diagnoses. Overall, focal neurological features such as seizure may occur in 0.36-1% of solid organ transplants with cerebral infection. [8] The preliminary laboratory and radiological investigations were not conclusive for a specific disease.

Based on the MRI, there were multiple ringenhancing lesions that were suggestive of TB; however, other causes such as toxoplasmosis, lymphoma, cysticercosis, pyogenic abscesses and glioma should be ruled out. [9] The CSF finding of predominant polymorphonuclear cells was not suggestive of TB in the absence of lymphocytic predominance. [10] Further, the negative CSF examination for M. tuberculosis, negative family history of TB, negative purified protein derivative and IGRA tests represented a diagnostic challenge for TB in our case. These negative diagnostic criteria of TB result in diagnostic delay and overuse of antibiotics in the patient. Although the histopathological picture was not conclusive of TB, a smear and culture of the specimen for M. tuberculosis confirmed the diagnosis. It has been documented that brain biopsy may be required for a definitive diag-nosis of brain lesion, which can be made through lessinvasive stereotactic techniques, as in our case. [11] A similar case was reported by our colleagues from Iran, who presented a patient with concurrent opportunistic infection of Aspergillus and M. tuberculosis of the CNS after a renal transplantation; however, the presentation of TB in their case was early, i.e. one month following the transplantation. [12]

In our report, the patient was treated successfully with a quadruple of anti-TB drugs. In the early course of treatment, the patient's neurological symptoms and signs continued to progress and he developed right-sided hemiparesis, which was assumed to be due to paradoxical expansion of the tuberculomas. [13] This was countered by an increasing dose of adjuvant corticosteroid therapy (prednisolone 60 mg/day for 1 month). Although pharmacological regimen is the mainstay of treatment, there is controversy regarding the management of intracranial tuberculomas. Chemotherapy alone may be sufficient, but when complicated by obstructive hydrocephalus, surgical intervention is indicated, especially when the patient's vision is threatened by severe intracranial hypertension. Tuberculomas can occur almost anywhere in the CNS, and may cause pressure effects, depending on their location.

The treatment was continued and an improvement of neurological signs was observed after two months of the chemotherapy. After six months, the patient's LOC improved and there was a decrease in the severity of hemiparesis. A repeated MRI showed marked reduction in the size of the lesions. The treatment is planned to be continued for at least 9-12 months based on the patient's clinical evaluation and response to therapy.

We conclude that cerebral tuberculoma should be considered in the differential diagnosis of multiple intracranial lesions, particularly in immunocompromised patients from endemic areas. Early diagnosis and treatment of intracranial tuberculoma are crucial in preventing morbidity and mortality of the condition.

 
   References Top

1.
World Health Organization. Global Tuberculosis Control: Epidemiology, Strategy, Financing. WHO Report 2009. WHO/HTM/TB/2009.411. Geneva, Switzerland: WHO; 2009.  Back to cited text no. 1
    
2.
Vachharajani T, Abreo K, Phadke A, Oza U, Kirpalani A. Diagnosis and treatment of tuberculosis in hemodialysis and renal transplant patients. Am J Nephrol 2000;20:273-7.  Back to cited text no. 2
    
3.
Simon HB, Weinstein AJ, Pasternak MS, Swartz MN, Kunz LJ. Genitourinary tuberculosis. Clinical features in a general hospital population. Am J Med 1977;63:410-20.  Back to cited text no. 3
[PUBMED]    
4.
DeAngelis LM. Intracranial tuberculoma: Case report and review of the literature. Neurology 1981;31:1133-6.  Back to cited text no. 4
[PUBMED]    
5.
Chang T, Rodrigo C, Ranawaka N, Atukorala I. Multiple ring-enhancing cerebral lesions in systemic lupus erythematosis: A case report. J Med Case Rep 2012;6:172.  Back to cited text no. 5
    
6.
Traub M, Colchester AC, Kingsley DP, Swash M. Tuberculosis of the central nervous system. Q J Med 1984;53:81-100.  Back to cited text no. 6
[PUBMED]    
7.
Whiteman ML. Neuroimaging of central nervous system tuberculosis in HIV-infected patients. Neuroimaging Clin N Am 1997;7:199-214.  Back to cited text no. 7
    
8.
Singh N, Husain S. Infections of the central nervous system in transplant recipients. Transpl Infect Dis 2000;2:101-11.  Back to cited text no. 8
    
9.
Rock RB, Olin M, Baker CA, Molitor TW, Peterson PK. Central nervous system tuberculosis: Pathogenesis and clinical aspects. Clin Microbiol Rev 2008;21:243-61.  Back to cited text no. 9
    
10.
van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 2004;351:1849-59.  Back to cited text no. 10
    
11.
Zunt JR. Central nervous system infection during immunosuppression. Neurol Clin 2002;20:1-22,v.  Back to cited text no. 11
    
12.
Petramfar P, Yousefian M, Ashraf MH, Davarpanah MA, Rahmati H. Meningoencephalitis with Aspergillus and mycobacterium tuberculosis in a renal transplant recipient. Exp Clin Transplant 2011;9:68-71.  Back to cited text no. 12
    
13.
Hejazi N, Hassler W. Multiple intracranial tuberculomas with atypical response to tuberculostatic chemotherapy: Literature review and a case report. Infection 1997;25:233-9.  Back to cited text no. 13
    

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Correspondence Address:
Muayad A Merza
Department of Internal Medicine, Faculty of Medical Sciences, University of Duhok, Azadi Hospital Street, Dohuk, Kurdistan, Iraq

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DOI: 10.4103/1319-2442.174163

PMID: 26787580

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