Role of Caspase- 3, TNF-α, and IL6 mRNA Expression in Intracranial Tuberculoma.

The development of tuberculoma is a process of inflammation, necrosis, and apoptosis. Therefore, the pro-inflammatory cytokines and apoptosis biomarkers are likely to play an important role. In this study, we report the expression of TNFα, IL6, and caspase-3 at the mRNA level in the patients with tuberculous meningitis (TBM) and compare these biomarkers in the patients with and without tuberculoma. A total of 134 patients with TBM and 35 matched healthy controls were included. The clinical, cerebrospinal fluid (CSF), and cranial magnetic resonance imaging (MRI) findings were noted. The mRNA expression of TNFα, IL6, and caspase-3 in peripheral blood mononuclear cells was evaluated by reverse transcriptase polymerase chain reaction. On cranial MRI, 89 (64.2%) patients had tuberculoma, and their level of consciousness, severity of meningitis, CSF findings, and blood counts were not significantly different from those without tuberculoma. Patients with tuberculoma had a higher expression of TNFα and IL6 compared to the controls, but had lower expression compared to the patients without tuberculoma. TNFα expression positively correlated with the expression of caspase-3, but not with IL6. Twenty-five (18.6%) patients died: 12 (13.5%) in tuberculoma and 13 (28.9%) in the non-tuberculoma group. Death was related to higher expression of TNFα and caspase-3. The lower expression of TNFα and IL6 in intracranial tuberculoma suggests that these patients are unlikely to be benefited with TNFα blockers.

Neurotuberculosis: A Clinical Review.

In September 2018, the United Nations General Assembly held the first ever meeting to discuss the global epidemic of tuberculosis (TB) and adopted a political declaration titled "United to end tuberculosis: an urgent global response to a global epidemic." The timing of the meeting was prescient but overdue since Mycobacterium tuberculosis surpassed the human immunodeficiency virus as the world's leading infectious killer in 2014. Infection of the central nervous system by Mycobacterium tuberculosis, herein referred to as neurotuberculosis, is the most feared and dangerous form of tuberculosis, requiring a high level of suspicion and clinical experience for prompt diagnosis and treatment. Neurologists, infectious disease specialists, orthopedic surgeons, neurosurgeons, and hospitalists in all countries need to recognize the spectrum of neurotuberculosis and be able to integrate clinical information, laboratory data, and radiological findings to make a diagnosis with or without microbiological confirmation.

Clinical and radiological spectrum of intracranial tuberculosis: A hospital based study in Northeast India.

Central nervous system tuberculosis (TB) is the most severe extra pulmonary TB having a high mortality and morbidity. OBJECTIVE: To study the various clinical, biochemical, and radiological spectrum of intracranial TB. MATERIALS AND METHOD: Ninety-three patients were enrolled in this prospective study after ethical clearance and consent from August 2013 to May 2015. The entire clinical course with complications and predictors of mortality were assessed. RESULTS: 36 females (38.7%) and 57 males (61.3%) were included whose mean age of presentation was 32.3±17.05 years. Alcohol was the most common risk factor seen in 19.4%. Headache (90.3%) was the most common symptom. Co-infection with human immunodeficiency virus, cryptococcal, and toxoplasmosis were seen in 11, 3, and 2 patients, respectively. Cerebrospinal fluid analysis showed acid-fast bacilli in 1 patient; polymerase chain reaction for TB and BACTEC was positive in one and three patients, respectively. Neuroimaging showed basal exudates (21.7%), tuberculoma (28.6%), brain edema (27%), hydrocephalus (32.9%), infarct (21%), and abscess (2.9%). Complications were noted such as brain edema (24.7%), vasculitis (26.9%), hydrocephalus (17.2%), hyponatremia (11.8%), drug-induced hepatitis (4.3%), and drug rash in 5 patients (5.4%). A total of 25 patients (26.9%) died and 38 patients (40.9%) developed neurological sequelae like hemiparesis, paraparesis, visual loss, and hearing loss. Logistic regression showed that a Glasgow scale of <10, British Medical Research Council stage 3, and vasculitis were associated with poor outcome. CONCLUSION: Lack of sensitive diagnostic method and criteria makes central nervous system TB a challenge where early diagnosis and prompt management is required.

Possible role of transforming growth factor ß in tuberculous meningitis.

BACKGROUND: Transforming growth factor ß (TGF-ß) is an anti-inflammatory cytokine and its role in hydrocephalus and stoke has been suggested. Tuberculous meningitis (TBM) is associated with exudates, stroke, hydrocephalus and tuberculoma, but the role of TGF-ß has not been evaluated in relation to these changes. AIM: To evaluate the cerebrospinal fluid (CSF) TGF-ß level in the patients with TBM, and correlate these with clinical findings, MRI changes, paradoxical response and outcome at 6months. METHODS: TBM patients diagnosed on the basis of clinical, CSF and MRI criteria were prospectively included. The clinical details including duration of illness, seizures, focal motor deficit, Glasgow Coma Scale (GCS) score and stage of TBM were noted. Presence of exudate, hydrocephalus, tuberculoma and infarction in MRI was also noted. MRI was repeated at 3months and presence of paradoxical response was noted. Cerebrospinal fluid TGF-ß was measured using ELISA on admission and repeated at 3months and these were compared with 20 controls. RESULTS: TGF-ß level was significantly higher in TBM compared to the controls (385.76±249.98Vs 177.85±29.03pg/ml, P<0.0001). TGF-ß correlated with motor deficit, infarction and tuberculoma on admission but did not correlate with CSF abnormalities, drug induced hepatitis, paradoxical response and outcome. TGF-ß level at 3months was significantly lower than the baseline but remained higher than the controls. CONCLUSION: CSF TGF-ß levels are elevated in TBM and correlate with infarction and tuberculoma.

Intracranial tuberculomas in adults: a report of twelve consecutive patients in Houston, Texas.

BACKGROUND: Intracranial tuberculomas are rare manifestations of tuberculosis (TB). An extensive literature review revealed that no study of consecutive adults with intracranial tuberculoma has been conducted in the USA. METHODS: This retrospective study consisted of 12 adults consecutively identified with intracranial tuberculomas from 1995 to 2009 in Houston, Texas. Of the 12 cases, 8 had a histopathological diagnosis, while 4 had a probable diagnosis based on the following criteria: (1) Mycobacterium tuberculosis identified from a source outside the brain, (2) radiographic confirmation of an intracranial mass, (3) received chemotherapy with 2 or more anti-tuberculosis medications, and (4) clinical response at 1-y follow-up. RESULTS: Common clinical manifestations were altered mental status, fever, and night sweats. Four patients (25%) had a human immunodeficiency virus (HIV) infection. Nine patients (75%) had concomitant M. tuberculosis at at least 1 extracranial site, including 5 patients with pulmonary TB. The median duration of therapy was 11 months. Patients had a 1-y mortality rate of 16.7% and an overall morbidity rate of 20%. CONCLUSIONS: Intracranial tuberculomas in Houston, Texas, are rare. Hospital discharge predicted survival at 1 y, despite severe clinical presentations and invasive diagnostic procedures. However, tuberculoma cases are associated with higher mortality rates than non-central nervous system TB cases.

Central system nervous tuberculosis in infants.

The lack of specific symptoms and signs in patients with tuberculous meningitis makes early diagnosis difficult. In this report, we reviewed the clinical features and laboratory findings of 6 infants with central system nervous tuberculosis during a 10-year period. One of the patients had multifocal tuberculosis. The mean time to the diagnosis was 32 +/- 13.4 days. A contact source was identified in only 2 patients. All 6 patients had abnormal cerebrospinal fluid findings, less than 500 cells/microL with lymphocytic predominance. Computerized tomography (CT) and/or magnetic resonance imaging (MRI) revealed hydrocephalus with basal enhancement in 2 patients. One patient developed pontocerebellar and pituitary tuberculomas, which were responsible for compression and diabetes insipidus, 1 year after antituberculous treatment. These localizations are very rare. On the follow-up, 3 patients had hypoacousia and only 1 had severe sequelae, despite a diagnostic delay.

[Intracranial tuberculoma in Africa, with no available neuroimaging. Case report and review of the literature]. / Tuberculome intracrânien en milieu africain sans neuro-imagerie. A propos d'un cas et revue de la littérature.

The numerous extrapulmonary manifestations of tuberculosis have been well described. Intracranial localizations, including brain stem tuberculoma, are very rare. The authors report a case of brain tuberculoma in a patient with a history of primary pulmonary tuberculosis successfully treated more than twenty years earlier. The patient presented with signs of infection, although the fever disappeared temporarily after successive treatments for malaria (confirmed Plasmodium faiciparum), as well as neurological signs with left hemiparesis. Chest radiographs showed no signs of progressive pulmonary tuberculosis, and blood tests, cerebrospinal fluid testing, and HIV serology were all negative. Treatments for maxillary sinusitis, the malaria, bacterial meningitis, and cerebral abscess were equally ineffective. Brain stem tuberculoma was diagnosed only when the patient was transferred to a hospital equipped with neuroimaging equipment and was confirmed after histopathological examination of the intracranial lesion biopsies and the detection of mycobacterium DNA by polymerase chain reaction (PCR) in the cerebrospinal fluid. A review of 147 cases of intracranial tuberculoma reported in Africa between 1985 and 2001 points out the difficulties of both the differential diagnosis (tuberculoma or other intracranial space-occupying lesions) and treatment in African areas where neuroimaging is unavailable. Our patient's brainstem tuberculoma probably resulted from reactivation of latent tuberculosis.

[Neuroradiologic manifestations of central nervous system tuberculosis in 122 adults]. / Manifestations neuroradiologiques initiales de la tuberculose du système nerveux central de l'adulte. A propos de 122 cas.

PURPOSE: Central nervous system (CNS) tuberculosis remains a public health problem, particularly in developing countries. The aim of this study is to characterize neuroradiologic findings of various intracranial lesions. METHODS: We retrospectively reviewed data of 122 patients with CNS tuberculosis, without immunosuppression. CT scan was performed in all patients, whereas 17 patients had CT scan and MRI. RESULTS: We included 74 women (61%) and 48 men (39%) with a mean age of 37 years (17 -88y). 18 patients (14,7%) had a history of tuberculosis. Tuberculous meningitis was the most frequent clinical presentation (119 cases). Mycobacterium tuberculosis was isolated in cerebrospinal fluid of 18 patients (15%). Several types of lesions were identified : hydrocephalus (35 cases), tuberculomas (29 cases), leptomeningitis (26 cases), infarction (15 cases), abcesses (2 cases). Hydrocephalus was associated to other lesions in 26 cases. Communication hydrocephalus was present in 28 cases. Multiple tuberculomas were seen in 23 cases (80%), with miliary aspects in some cases. In 3 cases, tuberculoma was present without meningitis. Patients with leptomeningitis showed thick meningeal contrast enhancement involving all basal cisterns. Infarction resulted from arterial englobement or embols, and involved the area of middle cerebral artery (12 cases). CONCLUSION: Central nervous system tuberculosis has different appearences, mostly hydrocephalus and tuberculomas. MR with contrast is necessary for diagnosis and for follow-up during treatment.

Case report: one-and-a-half-syndrome and tuberculosis of the pons in a patient with AIDS.

A patient with advanced AIDS presented with right conjugate gaze palsy and impaired adduction on left gaze (the one-and-a-half syndrome). The responsible pontine lesion involved the ipsilateral abducens nucleus and the adjacent medial longitudinal fasiculus (MLF), as demonstrated by magnetic resonance imaging (MRI). Tuberculosis (TB) was the etiology of the brainstem lesion. The patient had complete recovery after anti-tuberculosis treatment. The nuclear location of the tuberculoma is unusual and the reversal of this neuro-ophthalmologic syndrome is noteworthy.

Intracerebral tuberculoma in children with tuberculous meningitis.

Not all patients with tuberculosis develop tuberculoma during the disease or antituberculous therapy. Therefore, we compared various parameters in patients with and without tuberculoma and presented the results. We formed two groups from the patients with tuberculous meningitis: Group I consisted of 18 patients with tuberculoma, and Group II consisted of 18 randomly selected patients without tuberculoma. Significant difference between the groups was found with respect to level of consciousness and CSF-glucose level (p < 0.05). The consciousness level was more depressed and the CSF-glucose level more decreased in the group without tuberculoma. These findings were discussed.