Multiple tuberculomas in an immunocompetent patient and their diagnostic challenge in a high prevalence country: Case report and literature review.

CONTEXT: Intracranial tuberculomas are rare yet lethal forms of tuberculosis. Diagnosis is often difficult because of its nonspecific symptoms and radiological findings. AIM: This study aims to perform a literature review of multiple tuberculomas to improve disease recognition and management in immunocompetent patients along with presenting a case report on the topic. DATA SOURCES: Scopus, LILACS, Ovid MEDLINE and EMBASE. STUDY SELECTION: Case reports and case series up to December 2018 in English, Spanish, and Portuguese focusing on intracranial tuberculomas in adult and pediatric immunocompetent patients. Data on presentation, diagnostic workup, and treatment was analyzed. DATA EXTRACTION: Cochrane Collaboration/Cochrane Handbook and PRISMA guidelines. RESULTS: Twenty reports involving 21 patients were included. Most patients were male (57.14%). The average age at diagnosis was 26.9 ± 14.9 years. Headache was the most common presenting symptom (52.4%; 11/21), followed by motor weakness (47.6%; 10/21) and vomiting (23.8%; 5/21). MRI was the most used image technique (17/21). Most lesions occurring in the cerebral hemispheres (16/21); we found five or more lesions in 66.6% (14/21) of the patients. The majority treated with anti-tuberculous drugs resulted in a favorable outcome. CONCLUSIONS: Immunocompetent patients living in TB endemic areas whose clinical evaluation and neuroimaging findings are compatible with tuberculoma should undergo anti-tubercular treatment despite a lack of bacteriological confirmation.

Solitary intracranial tuberculoma in patients without immuno-suppression: a report of three cases.

BACKGROUND AND OBJECTIVE: Poverty, drug resistance and the advent of human immunodeficiency virus infection (HIV) have led to a recent upsurge in the incidence of tuberculosis including intracranial tuberculosis. In this article, we report 3 patients who had solitary brain tuberculomas and were otherwise healthy to underscore the importance of continuing vigilance for this disease. CASE REPORTS: Three patients (57 years, female; 52 years, male; 7 years male) presented to our unit with features of intracranial tumours. They were all HIV negative with no previous history of tuberculosis. Cranial computed tomography scans demonstrated uniformly contrast enhancing falcine supratentorial masses in the adult patients and a cerebellar hemispheric lesion with peripheral contrast enhancement in the paediatric patient INTERVENTION: All the patients had gross total tumour excision. The histology confirmed a tuberculoma. They all had antituberculous therapy after histological confirmation. The outcome was good in all the patients. CONCLUSION: Intracranial tuberculoma can occur in otherwise healthy individuals and should always be considered in the differential diagnosis of solitary intracranial mass lesions in sub-Saharan Africans so that minimally invasive procedures can be used to establish the correct diagnosis.

Multiple intracranial tuberculomas in a child.

Intracranial tuberculomas continue to be a serious complication of central nervous system tuberculosis. Tuberculomas are conglomerates of tubercles resulting from hematogenous spread of infection. Modern neuroimaging studies such as magnetic resonance imaging and molecular biologic techniques such as polymerase chain reaction are helpful in the diagnosis of central nervous system tuberculosis and tuberculomas. We report a boy with multiple intracranial tuberculomas diagnosed and treated with the aids of magnetic resonance and polymerase chain reaction techniques.

[Cerebral tuberculomas]. / Les tuberculomes cérébraux.

We report eight cases of brain tuberculoma. The clinical presentation was polymorphous: partial epilepsy (n=4), headache (n=3), hemiplegia (n=1), meningitis (n=1), cerebellar syndrome (n=1). Six patients also had pulmonary tuberculosis, one had tuberculosis of the genital organs, and one had HIV co-infection. The brain CT scan and MRI were highly contributive to diagnosis and follow-up. Despite good compliance with an anti-tuberculosis regimen for at least 14 months, the course was favorable in only six patients. Adjunction of corticosteroids led to radiological improvement. Assessment of cell immunity demonstrated a diminished immunomodulator ratio. Cerebral tuberculoma should be searched for in patients with unexplained neurological manifestations and several intracerebral lesions, particularly if pulmonary or visceral tuberculosis and/or immunodepression is part of the clinical picture.

[Paradoxical appearance of encephalic tuberculomas during treatment for tuberculosis in immunocompetent patients]. / Aparición paradójica de tuberculomas encefálicos durante el tratamiento de tuberculosis en pacientes inmunocompetentes.

Two cases of appearance of encephalic tuberculomas during anti-tuberculous treatment in immunocompetent patients are presented. The first an adult man presenting a right frontal lesion which required surgical treatment and the second a girl with multiple lesions located mainly in the brainstem. This paradoxical presentation is attributed to a bizarre immunological reaction between the host and the tuberculosis bacillus. Patients with this condition do not require changes in anti-tuberculous treatment, and steroids are helpful in alleviating the symptoms. Surgery is indicated only for cases of uncontrollable intracranial hypertension or when there is diagnostic uncertainty. The prognosis of this entity is usually good.

[Multiple cerebral tuberculomas resistant to conventional therapy in an immunocompromised subject]. / Tubercolomi cerebrali multipli resistenti alla terapia convenzionale in un soggetto immunosoppresso.

A 33 years old immunocompromised woman was admitted for a fever of unknown origin during the last five months. She referred a body temperature up to 38.3 degrees C, headache, weakness. The physical examination revealed right homonymous hemianopia, hyperreflexia and Babinski on her right side. A TC scan and a following bioptic specimen showed multiple cerebral tuberculomas. A conventional therapy was started but no significative improvement was observed. She was finally treated with interferon gamma and GM-CSF in addition to the therapy with an important regression of the lesions and significative improvement of the fever and neurological findings.

Recurrent immune reconstitution inflammatory syndrome of tuberculous brain infection in people living with HIV/AIDS: a case report.

HIV infection has changed the scenario of infectious disease. HIV-associated immunodeficiency resulted in a wide spectrum of new opportunistic infections. After introduction of antiretroviral therapy (ART), immune reconstitution inflammatory syndrome (IRIS) became an important challenge in management of 10% to 25% of the patients. Meta-analyses of IRIS from various reports published worldwide by Monika Muller et al described 12% IRIS incidence and 15.7% IRIS tuberculosis. Among IRIS tuberculosis, central nervous system involvement with IRIS tuberculous meningitis forms only 7%. Only 9 cases of tuberculous brain abscess is reported in patients with AIDS so far. The IRIS tuberculous brain abscess is very rare, and so far only 1 case is reported as a paradoxical reaction after ART initiation. Here, we report a case of recurrent IRIS tuberculosis meningitis and brain abscess.

Intracranial tuberculoma in non-immunosuppressive state.

The rise in the incidence of tuberculosis is generally related to human immunodeficiency virus infection. However, intracranial tuberculoma, a complication of tuberculosis considered to be a critical disease, can develop even in the absence of immunosuppressive state. Here, we describe 2 cases of intracranial tuberculoma occurring in patients with no evidence of immunosuppressive state or past history of tuberculosis. In Case 1, lesions were observed in the right lateral ventricle, with histological examination revealing granulomatous lesions. In Case 2, scattered lesions were observed in the cranium and the lung fields. In both cases, the QuantiFERON Test (QFT) was positive, and improvements were observed in the symptoms following administration of antituberculous drugs. Intracranial tuberculoma cannot be considered rare, and needs to be included in the differential diagnosis of intracranial lesions. Diagnosis can be tricky since this disease can develop in a patient in a non-immunosuppressive state or without a past history of tuberculosis. The QFT is an effective test to enable the diagnosis of tuberculomas in atypical patients.

Neurocysticercosis case with tuberculoma-like epithelioid granuloma strongly suspected by serology and confirmed by mitochondrial DNA.

An Indian woman with multiple and nodular cerebral lesions presenting epithelioid granulomas was diagnosed as suspected malignant tumours and the biopsy was carried at local hospital in Japan. The specimen was pathologically diagnosed as tuberculoma. However, due to her nationality, the authors suspected it to be neurocysticercosis (NCC) and carried out serology and applied mitochondrial DNA analysis of Taenia solium. These diagnostic tools revealed it as NCC radiologically and pathologically mimicking central nervous tuberculomas. Molecular confirmation of NCC cases is strongly recommended when we can get the biopsy specimens.

Rapid diagnosis of CNS tuberculosis by a T-cell interferon-gamma release assay on cerebrospinal fluid mononuclear cells.

Central nervous system tuberculosis remains a clinical diagnostic challenge. The ex vivo Mycobacterium tuberculosis-specific enzyme-linked immunospot assay (ELISPOT) is a novel assay for the rapid detection of M. tuberculosis-specific T-lymphocytes in the peripheral blood. However, when performed on peripheral blood, this assay cannot distinguish between active tuberculosis or latent tuberculosis infection. On the assumption that M. tuberculosis-specific T-lymphocytes migrate to sites of infection, we were able to demonstrate high levels of M. tuberculosis-specific cells by ELISPOT in the cerebrospinal fluid of a patient with tuberculous meningitis and intracerebral tuberculoma four weeks before cerebrospinal fluid culture became positive for M. tuberculosis by culture.

Disseminated tuberculosis with multiple intracerebral tuberculomas in a patient with anorexia nervosa.

OBJECTIVE: Multiple tuberculous mycobacterial infections infrequently occur in immunocompromised patients. The malnutrition resulted from anorexia nervosa may contribute to the significant impairment of immunity. The authors present a 23-year-old female patient initially diagnosed with anorexia nervosa. METHOD: Immunological study revealed that helper T-cell (CD4) and cytotoxic T-cell (CD8) comprised 25 and 32%, respectively, with a CD4 to CD8 ratio of 0.78. Brain magnetic resonance imaging revealed various multiple rings enhancing lesions with edematous change in both cerebral and cerebellar hemispheres. RESULTS: Open biopsy disclosed palisading epithelioid granuloma surrounded by inflamed granulation tissue. After anti-tuberculous therapy for 12 months, her weight was completely restored, but multiple intracranial tuberculomas were not completely disappeared. CONCLUSION: Disseminated tuberculous mycobacterial infections including multiple intracranial tuberculomas may be attributed to immunocompromised status in anorexia nervosa.

Relationship between intracranial granulomas and cerebrospinal fluid levels of gamma interferon and interleukin-10 in patients with tuberculous meningitis.

Cerebrospinal fluid gamma interferon (IFN-gamma) and interleukin-10 levels in 39 patients with tuberculous meningitis were serially measured. Cytokine levels did not predict intracranial granuloma (IG) development, but IFN-gamma levels in the top quartile after 1 month of therapy were highly associated (odds ratio = 18) with detection of an IG by computed tomography scanning.