Blood-CSF-barrier permeability in tuberculous meningitis and its association with clinical, MRI and inflammatory cytokines.

Blood -cerebrospinal fluid-barrier (BCB) disruption in tuberculous meningitis (TBM) may be mediated by inflammatory cytokines, and may determine clinico-radiological severity and outcome. We report BCB permeability in TBM and its relationship with inflammatory cytokines (TNF-α, IL-1ß and IL-6), clinical severity, MRI changes and outcome. 55 TBM patients with a median age of 26 years were included. Their clinical, cerebrospinal fluid (CSF) and MRI findings were noted. The severity of meningitis was graded into stages I to III. Cranial MRI was done, and the presence of exudates, granuloma, hydrocephalus and infarctions was noted. BCB permeability was assessed by a ratio of CSF albumin to serum albumin (Qalb). The concentration of TNF-α, IL-1ß and IL-6 in CSF were measured by cytokine bead array. The Qalb in the patients was more than the mean + 2.5 SD of controls. In TBM, Qalb correlated with TNF- α (r = 0.47; p = 0.01), CSF cells (r = 0.29; p = 0.02) and exudate on MRI (0.18 ± 0.009 Vs 0.13 ± 0.008; p = 0.04). There was however no association of Qalb with demographic variables, stage, tuberculoma, infarction and hydrocephalus. At 6 months, 11(20%) died, 10(18.2%) had poor and 34(61.8%) had a good recovery. BCB permeability in TBM correlated with TNF-α, CSF pleocytosis and exudates but not with severity of meningitis and outcome.

Cerebrospinal fluid analysis is associated with enhancement on MRI in bacterial and tuberculous meningitis: A retrospective observational study.

OBJECTIVE: Along with cerebrospinal fluid (CSF) analysis, enhancement on contrast-enhanced MRI is useful to diagnose meningitis. However, the conditions for its appearance have not been clarified. This study aimed to investigate the association between CSF parameters and enhancement on contrast-enhanced head or spinal MRI in patients with bacterial meningitis (BM) or tuberculous meningitis (TM). METHODS: A total of 12 patients with BM and 23 patients with TM who underwent both CSF analysis and contrast-enhanced MRI were included. The correlation between CSF analysis and MRI findings has been examined using receiver operating characteristic (ROC) analysis. RESULTS: Contrast enhancement was found in 7 and 10 patients with BM and TM, respectively. Both CSF analysis and MRI were useful to distinct between BM and TM, and the enhancement implied the severity of them. In patients with BM, higher CSF protein and lower CSF glucose were associated with enhancement on MRI, while not only CSF protein and glucose but also leukocyte and lymphocyte counts were associated with it in TM. CSF adenosine deaminase (ADA) did not show discriminant ability of the MRI findings. CONCLUSIONS: CSF analysis is associated with enhancement on contrast-enhanced MRI both in BM and TM. Our findings indicate the importance of CSF analysis in assessing the need to perform contrast-enhanced MRI, which may be useful in diagnosis, distinction, and estimation of prognosis in those patients.

Predictors of fever response in tuberculous meningitis: A clinical, MRI and biomarker study.

BACKGROUND: Central nervous system (CNS) has a different immune surveillance system; therefore, fever at admission and timeline of fever response after antitubercular treatment (ATT) may follow a different course in CNS infection. We report the predictors of fever response in tuberculous meningitis (TBM) including the effect of tumour necrosis factor-α (TNF-α) in cerebrospinal fluid (CSF) and its gene expression at mRNA of peripheral blood mononuclear cells (PBMCs). METHODS: Fifty-seven patients with TBM were prospectively evaluated. Their clinical findings and severity of meningitis were recorded. The expression of TNF-α gene in PBMCs was quantified by real-time polymerase chain reaction and TNF-α concentration in CSF by cytokine bead array both in the patients and 14 matched controls. RESULTS: All the patients had history of fever for a median duration of 75 days. The admission temperature ranged between 37.2°C and 40°C and correlated with CSF cell counts (p < 0.05). Cranial MRI was abnormal in 54 (94.7%) and revealed exudates in 33(57.9%), hydrocephalus in 27(47.4%), infarction in 27(47.4%) and tuberculoma in 33(57.9%) patients. Fever subsided after a median duration of 18 (2 60) days of treatment. Twelve (21.8%) patients only became afebrile within 10 days. The expression of TNF-α gene correlated with CSF concentration of TNF-α (p = 0.02) and independently predicted duration of defervescence [adjusted hazard ratio 1.02 (95% CI 1.00-1.04; p = 0.01). CONCLUSION: In the patients with TBM, defervescence takes longer time, and TNF-α gene expression predicts the duration of defervescence. Future studies are needed to evaluate the role of TNF-α-modifying drugs in TBM.

Longitudinal cerebrospinal fluid assessment in a patient with tuberculous meningitis-A case report.

BACKGROUND: Dynamic assessment of cerebrospinal fluid (CSF) is essential for diagnosis, treatment, and prognosis of tuberculous meningitis, one of the most severe forms of central nervous system (CNS) infection. CASE PRESENTATION: A 45-year-old man sought care as he developed confusion, clonic convulsion, and coma. Longitudinal, comprehensive analyses of cytological, biochemical, and microbial changes in CSF specimen were assessed for this patient. On day 1 of hospitalization, modified Ziehl-Neelsen staining of CSF identified positive acid-fast bacilli, cytological analysis revealed neutrophilic-predominant pleocytosis (neutrophils 77%), and adenosine deaminase (ADA) was substantially elevated. Therefore, tuberculous meningitis was diagnosed and first-line standard anti-tuberculosis treatment was initiated. Interestingly, after 7-day treatment, the patient was greatly improved, and CSF disclosed a dominant percentage of lymphocytes (82%) as well as macrophages engulfing Mycobacterium tuberculosis. Later, the dose of dexamethasone was reduced, large number of neutrophils (57%) was present and protein level was immediately elevated in CSF specimen, indicating a possible relapse of tuberculous meningitis. Since the clinical condition of the patient was not worsening, the patient was stick to reduced dose of dexamethasone and standard anti-tuberculosis agents. He was discharged from the hospital on day 34, with 1-year continuation standard anti-tuberculosis therapy, and was clinically resolved from tuberculous meningitis. CONCLUSION: Detailed analyses of cellular composition, biochemical results, and microbial tests of CSF specimen provide the physician direct evidence of the immune surveillance status during tuberculous meningitis, which facilitates early diagnosis, optimal treatment, and improved prognosis.

Extrapulmonary Tuberculosis: Pathophysiology and Imaging Findings.

Extrapulmonary tuberculosis (TB) represents approximately 15% of all TB infections. It is difficult to diagnose on the basis of imaging characteristics and clinical symptoms, and biopsy is required in many cases. Radiologists must be aware of the imaging findings of extrapulmonary TB to identify the condition in high-risk patients, even in the absence of active pulmonary infection. In extrapulmonary TB, the lymphatic system is most frequently affected. The presence of necrotic lymph nodes and other organ-specific imaging features increases the diagnostic probability of extrapulmonary TB. Disseminated infection and central nervous system involvement are the most frequent manifestations in immunosuppressed patients. Renal disease can occur in immunocompetent patients with very long latency periods between the primary pulmonary infection and genitourinary involvement. In several cases, gastrointestinal, solid-organ, and peritoneal TB show nonspecific imaging findings. Tuberculous spondylitis is the most frequent musculoskeletal manifestation. It is usually diagnosed late and affects multiple vertebral segments with extensive paraspinal abscess. Articular disease is the second most frequent musculoskeletal manifestation, and synovitis is its predominant imaging finding.©RSNA, 2019.

Role of Oxidative Stress in Tuberculous Meningitis: a Clinico-Radiological Correlation.

Central nervous system infection may be associated with oxidative stress and may influence clinical severity and outcome. We report oxidative stress markers in the patients with tuberculous meningitis (TBM) and correlate these with clinico-radiological severity and outcome. Fifty-six patients with TBM diagnosed on the basis of clinical, cerebrospinal fluid (CSF), and magnetic resonance (MRI) were included. Plasma glutathione (GSH), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured in the patients and 55 matched healthy controls. Hospital death was noted. Disabilities at 3 and 6 months were categorized using the modified Rankin Scale (mRS) as poor (mRS > 2) or good (mRS ≤ 2). The patients had lower levels of GSH (1.49 ± 0.49 vs 2.57 ± 0.39 mg/dL, p Ë‚ 0.001) and TAC (0.25 ± 0.17 vs 2.20 ± 0.31 mmol Trolox Eq/L, p Ë‚ 0.001), and higher level of MDA (6.61 ± 1.72 vs 3.09 ± 0.38 nmol/mL, p < 0.001) compared to controls. Total antioxidant capacity correlated with cranial nerve palsy and CSF pleocytosis. Patients with tuberculoma had lower GSH compared to those without. Six patients died in the hospital, and they had lower GSH (p < 0.01) and TAC (p = 0.02) levels compared to those who survived. Thirty-one and 36 patients had a good outcome at 3 and 6 months respectively. The patients with good outcome had higher GSH level.

Imaging in Pediatric Extra-Pulmonary Tuberculosis.

Extrapulmonary tuberculosis in children tends to be more severe than the adults. It can affect almost any organ system of the body. The clinical manifestations are often non-specific. Imaging findings are also not always very specific. This article describes the imaging spectrum of pediatric extrapulmonary tuberculosis.

Hypothalamic and pituitary dysfunction is common in tubercular meningitis: A prospective study from a tertiary care center in Northern India.

INTRODUCTION: Current literature is poor with respect to well conducted prospective studies of hypothalamic pituitary axis (HPA) dysfunction in tubercular meningitis (TBM). As hormonal deficiencies are associated with poor clinical outcome in various neurological and non-neurological disorders, we prospectively evaluated the hypothalamic pituitary axis (HPA) dysfunction in TBM. PATIENTS AND METHODS: Present study included newly diagnosed drug naive TBM patients (n = 63) at a tertiary care centre in Northern India. All patients underwent detailed clinical, radiological evaluation (Gadolinium enhanced magnetic resonance imaging of brain) and HPA hormonal profiles (electrochemiluminescence assay) both at initial presentation and at six month follow up. All the data was recorded on a predesigned proforma. RESULTS: 77.8% patients had definite and 22.2% had highly probable TBM. 84.2% of patients had pituitary hormonal abnormalities at presentation. These included hyperprolactinemia (49.2%), secondary adrenal deficiency (42.9%), secondary hypogonadism (38.1%) and central hypothyroidism (9.5%). At follow up, 42.1% patients had HPA abnormalities [hyperprolactinemia (13.2%), secondary hypogonadism (15.8%), secondary adrenal deficiency (10.5%) and central hypothyroidism (10.5%)]. On multivariate logistic regression analysis, secondary hypocortisolism (Odd ratio: 4.042; 95% CI = 1.074-15.22; P = .039) was associated with poor outcome in TBM. CONCLUSION: Abnormalities of HPA are common in TBM. Patients with TBM should be evaluated for dysfunction of HPA and treated accordingly.

Concurrent Intramedullary and Intracranial Tuberculomass.

Tuberculosis of the central nervous system (CNS) is well known. CNS involvement can occur in the form of tubercular meningitis (TBM), tuberculous vasculitis, tuberculoma and rarely brain abscess. Tubercular granulomas generally solitary and occur in the brain but they may be multiple and involve other areas such as spinal cord, epidural space and subdural space also. Tuberculoma in the spinal cord is rare. Co-occurrence of intracerebral and intramedullary spinal tuberculoma is extremely rare in children with only few cases reported till date. We are reporting one such case in children and review of literature.

Central nervous system blast crisis of chronic myeloid leukaemia misdiagnosed as tubercular meningitis.

Chronic Myeloid Leukaemia (CML) presenting with isolated Central Nervous System (CNS) blast crisis is an uncommon entity. A 22-year-old man, diagnosed with chronic phase CML in 2011 and was in haematological and cytogenetic remission until July 2016, had acute onset headache and vomiting with meningeal signs and was admitted elsewhere, investigated by brain imaging and cerebrospinal fluid (CSF) analysis and suspected to have tubercular meningitis, for which steroids and antitubercular medications were started. The patient's sensorium further deteriorated, and Ventriculoperitoneal shunt surgery was done for hydrocephalus by a neurosurgeon. After 2 months of the illness, he was admitted to our hospital with a persistent headache, vomiting and altered sensorium. CSF for cytospin confirmed myeloid blasts. He was still in haematological remission. So, a diagnosis of isolated CNS blast crisis was made. The patient was started on triple intrathecal chemotherapy and cranial radiotherapy. He had improvement with treatment and is still in remission.

Role of Immuno-Polymerase Chain Reaction (I-PCR) in Resolving Diagnostic Dilemma Between Tuberculoma and Neurocysticercosis: A Case Report.

BACKGROUND Tuberculoma and neurocysticercosis (NCC) often show similar clinical and neuroimaging features. Differential diagnosis of these 2 diseases is imperative, as tuberculoma is an active infection that requires immediate anti-tubercular therapy (ATT). CASE REPORT We present the case of a 17-year-old Indian girl with fever, severe headache, and right 6th cranial nerve palsy. Brain magnetic resonance imaging (MRI) showed multiple tiny ring-enhancing lesions in bilateral cerebral parenchyma with mild perilesional edema, which were initially thought to be NCC, but subsequently were diagnosed as brain tuberculomas. Based on clinical findings, mildly increased choline/creatine ratio (1.35) with slight prominent lipid lactate peak and absence of alanine, succinate peak by magnetic resonance spectroscopy (MRS), and the detection of Mycobacterium tuberculosis (Mtb)-specific early-secreted antigenic target-6 (ESAT-6, Rv3875) protein from the cerebrospinal fluid (CSF) by indirect ELISA, as well as indirect immuno-PCR (I-PCR) assay, diagnosis of brain tuberculomas associated with tuberculous meningitis (TBM) was confirmed, which was followed by ATT. The patient responded well and the symptoms resolved. CONCLUSIONS In this case, multiple ring-enhancing lesions of the brain by MRI were diagnosed as tuberculomas associated with TBM by MRS and indirect ELISA/I-PCR method, thus resolving the diagnostic dilemma.

Concurrent intramedullary spinal cord and multiple intracranial tuberculomas with tuberculous optic neuritis: A rare case report.

Tuberculosis (TB) remains a worldwide burden, with a large majority of new active TB cases occurring in underdeveloped and developing countries. Tuberculous meningitis (TBM) is one of the common infections of central nervous system. Other manifestations include intracranial tuberculoma, tubercular brain abscess, spinal tuberculoma, and granulomatous arachnoiditis. Visual impairment in TBM may be due to optic neuritis, optochiasmatic arachnoiditis (OCA), tuberculoma in the chiasmatic region or in the optic pathways, chorioretinitis, secondary to hydrocephalus and increased intracranial pressure, and finally due to ethambutol toxicity. We report a case of young girl with concurrent spinal cord intramedullary tuberculoma and multiple intracranial tuberculomas with TBM and bilateral visual impairment due to tuberculous optic neuritis.

Cerebral and Spinal Tuberculous Leptomeningitis: Advanced Magnetic Resonance Imaging Findings.

At diagnosis of the cerebral and spinal tuberculous meningitis magnetic resonance (MR) imaging is the primary imaging technique. Magnetic resonance images reveal cerebrospinal fluid collection and obliteration of the spinal subarachnoid space. The contrast-enhanced MR imaging shows nodular and thick intradural enhancement. Herein, the authors reported advanced MR imaging findings of the cerebral and spinal tuberculous leptomeningitis.

Neuroimaging in tuberculous meningitis.

Tuberculous meningitis is a serious infection caused by Mycobacterium tuberculosis. Early diagnosis is the key to success of treatment. Neuroimaging plays a crucial role in the early and accurate diagnosis of tuberculous meningitis and its disabling complications. Magnetic resonance imaging is considered superior to computed tomography. Neuroimaging characteristics include leptomeningeal and basal cisternal enhancement, hydrocephalus, periventricular infarcts, and tuberculoma. Partially treated pyogenic meningitis, cryptococcal meningitis, viral encephalitis, carcinomatous, and lymphomatous meningitis may have many similar neuroimaging characteristics, and differentiation from tuberculous meningitis at times on the basis of neuroimaging characteristics becomes difficult.

[Multiple meningeal and cerebral involvement revealing multifocal tuberculosis in an immunocompetent patient]. / Atteinte cérébro-méningée multiple révélant une Tuberculose multifocale chez un immunocompétent.

Tuberculosis is a public health problem in Morocco. Central nervous system involvement is nevertheless rare, occurring in the context of multifocal or miliary tuberculosis. However, it may be a mode of revelation even in an immunocompetent subject. We report the case of a 30-year old man with language disorder accompanied by significant impairment of general condition. Clinical examination showed Broca's motor aphasia, right-sided pyramidal syndrome and latero-cervical adenopathies. HIV serologic test was negative. Brain MRI showed lesions associating multiple intracranial tuberculomas and meningoencephalitis. Thoracic CT scan showed multiple pulmonary micronodules, cavity wall thickening and bronchiectasia of the right fowler and culmen. Lymph node biopsy revealed typical architecture of a TB granuloma. The diagnosis of multifocal tuberculosis was retained and the patient received anti-bacillary therapy associated with corticosteroid therapy with good clinico-radiological evolution. This study is peculiar due to the appearance and the seat of tuberculous lesions on brain imaging, the absence of immunodeficiency, a good evolution under treatment. It highlights the role of active and exhaustive assessment of associated extracerebral tuberculous infection in the case of cerebromeningeal lesion suggestive of tuberculosis.

Tubercular Meningitis on 18F-FDG PET/CT: Incidentally Detected and Masquerading as Relapse in a Patient With Ovarian Burkitt Lymphoma.

Tuberculosis can mimic malignancy, both clinically as well as on ¹8F-FDG PET/CT, leading to false-positive lesions. We present such a case of a 14-year-old female patient with ovarian Burkitt lymphoma treated with chemotherapy. On post-therapy PET/CT, ¹8F-FDG avid meningeal enhancement was seen which was suspicious for distant relapse versus tubercular meningitis. On cerebrospinal fluid examination, diagnosis of tubercular meningitis was confirmed.