OBJECTIVE

Early diagnosis and treatment of tuberculous meningitis (TBM) is essential for a positive outcome, but sensitive, specific, and rapid diagnostic tests for TBM are lacking. We evaluated the diagnostic utility of enzyme-linked immunosorbent spot (ELISPOT) assays in HIV-uninfected patients with suspected TBM.

METHODS

All HIV-uninfected patients with suspected TBM were prospectively enrolled at a tertiary care hospital in an intermediate TB-burden country, during a 6-year period. ELISPOT assays were performed on peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid-mononuclear cells (CSF-MC).

RESULTS

Of the 276 evaluable patients, 90 (33%) were classified as having TBM (30 definite cases, 19 probable, and 41 possible), and 186 (67%) as having non-TBM. When comparing definite TBM versus non-TBM, the sensitivity and specificity of the PBMC ELISPOT assay (≥6 spots; manufacturer's recommended cut-off) for diagnosing TBM were 96% (95% CI, 82-100) and 58% (95% CI, 50-66), respectively. The CSF-MC ELISPOT assay (≥38 spots; receiver operating characteristic [ROC]-derived cut-off) was a useful rule-in test with specificity of 95% (96% CI, 90-98). Its sensitivity was 68% (95% CI, 45-86), which was superior those of AFB smear microscopy (14%; P < 0.001) and CSF Mycobacterium tuberculosis PCR (41%; P = 0.07). Combining this assay with M. tuberculosis PCR, clinical score, and both together increased sensitivity to 86%, 91%, and 95%, respectively, while retaining about 95% specificity.

CONCLUSIONS

The CSF-MC ELISPOT assay appears to be a rapid and accurate rule-in test for the diagnosis of TBM and a useful adjunct for diagnosing TBM in HIV-uninfected patients.

OBJECTIVE

This study aims at evaluating the clinical and radiological outcome of tuberculous meningitis (TBM) patients with pulmonary miliary tuberculosis.

METHODS

Diagnosis of TBM was based on clinical, CT scan or MRI and CSF criteria, and that of miliary tuberculosis on chest radiograph. Detailed clinical evaluation was done in all. Severity of meningitis was graded into Grades I, II and III. Complete hemogram, serum chemistry and Montaux tests were performed. The recovery was defined on the basis of 6 months Barthel index score as poor, partial or complete.

RESULTS

20 out of 165 patients with TBM had pulmonary miliary tuberculosis. Their mean age was 30 years; there was one child and 13 patients were females. The mean duration of symptoms was 6.3 months. Montoux test was negative in 9 patients. Six patients were in stage I, 3 in stage II, and 11 in stage III meningitis. Hemoglobin was below 12 gm% in 13 and liver dysfunction and hypocalcaemia was present in 8 and 18 patients respectively. CT scan was abnormal in 16 patients and revealed hydrocephalus (10), granuloma (7), exudates (3) and infarction (1). MRI was abnormal in 7 out of 8 patients and 3 of these patients had normal CT scan. MRI revealed multiple granuloma in 7 patients and exudates in 2. At 6 months, 2 patients died, 10 had complete, 2 had partial and 4 had poor recovery.

CONCLUSIONS

TBM with pulmonary miliary tuberculosis was commoner amongst females who were anemic and hypocalcaemic. MRI revealed multiple granuloma and the majority of the patients improved.

Neurological symptoms in childhood miliary tuberculosis are generally caused by underlying tuberculous meningitis (TBM), since the 2 conditions commonly occur concurrently. Cerebral infarction, a well-recognized complication of TBM, usually results from tuberculous periarteritis and secondary thrombosis. Neuropathological studies have demonstrated that the anterior cerebral circulation is more commonly affected than the arteries of the vertebro-basilar system, and basilar artery occlusion as a presenting manifestation of childhood miliary tuberculosis or TBM has not been described before. We report a 13-month-old infant who presented with fever and convulsions, terminating in acute decerebration after a second prolonged seizure 1 week after the onset of symptoms. Magnetic resonance (MR) imaging demonstrated density changes compatible with acute vertebro-basilar ischemia as well as multiple cerebral granulomas. A chest radiograph showed diffuse miliary tuberculosis. Postmortem examination confirmed this diagnosis and revealed acute occlusion of the basilar artery by an infected (septic) thromboembolus showing granulomatous inflammation, which most likely arose from an endocardial vegetation with identical histology.

OBJECTIVE

Tuberculous meningitis (TBM) is a debilitating form of CNS tuberculosis with a high morbidity and mortality in spite of treatment. The diagnosis is based on clinical, radiological and laboratory features. The classical CT features of basal exudates, hydrocephalus, infarcts and granulomas have been mostly reported in younger individuals. Our aim was to study imaging features of TB meningitis in adults over the age of 50 years.

METHODS

Clinical, imaging and laboratory features of 53 adult patients over the age of 50 years (sixth to eighth decades) were studied retrospectively. Diagnosis of TBM was based on clinical and laboratory features.

RESULTS

Imaging features were the conspicuous absence of typical features of TBM (ie, basal meningeal enhancement, hydrocephalus, infarcts/granulomas were seen in only a minority of patients).

CONCLUSIONS

CT features of TBM in elderly patients were few, atypical and non-contributory for diagnosis, probably because of age related immune senescence. Strong clinical suspicion and correlation with laboratory findings is necessary for early diagnosis.

OBJECTIVE

Tuberculosis (TB) is a public health problem worldwide. Rapid and accurate diagnosis of tuberculosis is crucial to facilitate early treatment of infectious cases and to reduce its spread. The present study was aimed to evaluation of 16 kDa antigen as a serodiagnostic tool in pulmonary and extra-pulmonary tuberculosis patients in an effort to improve diagnostic algorithm for tuberculosis.

METHODS

In this study, 200 serum samples were collected from smear positive and culture confirmed pulmonary tuberculosis patients, 30 tubercular pleural effusions and 21 tubercular meningitis (TBM) patients. Serum samples from 36 healthy, age matched controls (hospital staff), along with 60 patients with non-tubercular respiratory diseases were also collected and evaluated. Humoral response (both IgG and IgA) was looked for 16 kDa antigen using indirect ELISA.

RESULTS

Sensitivity of detection in various categories of pulmonary TB patients ranged between 73.8 and 81.2 per cent. While in the extra-pulmonary TB samples the sensitivity was 42.8 per cent (TBM) and 63.3 per cent (tubercular pleural effusion). The test specificity in both the groups was high (94.7%). All of the non-disease controls were negative. Among non-tubercular disease controls, five patients gave a positive humoral response against 16 kDa.

CONCLUSIONS

Serodiagnostic tests for TB have always had drawbacks of suboptimal sensitivity and specificity. The antigen used in this study gave encouraging results in pulmonary TB only, while in extra-pulmonary TB (tubercular meningitis and tubercular pleural effusion), this has shown a limited role in terms of sensitivity. Further work is required to validate its role in serodiagnosis of TB especially extra-pulmonary TB.

Enzyme-linked immunosorbent assay (ELISA) was standardized and evaluated for detection of antibody response in cerebrospinal fluid (CSF) to antigens of Mycobacterium tuberculosis and Cysticercus cellulosae. Sonicated extracts of heat killed M. tuberculosis H37Rv and C. cellulosae were prepared and used in ELISA to detect respective antibody response in CSFs for a definitive diagnosis as to tuberculous meningitis (TBM)/neurocysticercosis (NCC). ELISA was performed in a total of 201 CSF samples, which include Group I: chronic infections of the central nervous system (CNS) with possible diagnosis of TBM, tuberculoma, or NCC (n = 70), and Group II: control group of patients with infectious neurological (n = 19), non-infectious neurological (n = 82), and non-infectious non-neurological conditions, i.e., spinal anaesthesia CSFs (n = 30). Specificity in this study was 99.9% and no true cross-reactivity between antimycobacterial antibodies and C. cellulosae antigens and vice-versa was observed. However, in 17.14% of CSFs (12/70), both antimycobacterial and anticysticercal antibodies were detected, 50% of these cases were diagnosed as TBM. But none of the proven NCC cases showed presence of antimycobacterial antibodies. Results of this study would indicate that it would be beneficial if both antibody and antigen responses are detected in CSFs to infectious aetiologies such as M. tuberculosis, C. cellulosae, and C. neoformans in order to enhance the diagnostic accuracy and proper management, as these diseases are highly endemic in underdeveloped and developing countries.

Tuberculosis (TB) is a serious public health problem. Development of experimental models and vaccines are essential to elucidate physiopathological mechanisms and to control the disease. Vascular endothelial growth factor (VEGF) is a potent activator of vascular permeability and angiogenesis. VEGF seems to participate in breakdown of the blood brain-barrier (BBB) in tuberculous meningitis (TBM), contributing to worsening of disease. Therefore, the objective here was to extent the characterization of our previously described murine model of central nervous system TB (CNS-TB) by describing the VEGF participation in the CNS disease, and suggesting a vaccination plan in mice. Plasmid encoding DNA protein antigen DNA-hsp65 has been described as a protector against TB infection and was used here to test its effectiveness in the prevention of VEGF production and TB disease. Vaccinated mice and its controls were injected with Mycobacterium bovis bacillus Calmette-Guerin (BCG) in cerebellum. Four weeks after BCG injection, mice were perfused and brains were paraffin-embedded for VEGF expression analysis. We observed VEGF immunohistochemical expression in TBM and granulomas in non-vaccinated mice. The DNA-hsp65 treatment blocked the expression of VEGF in mice TBM. Therefore, our murine model indicated the VEGF participation in the physiopathology of CNS-TB and the potential prevention of the DNA-hsp65 in the disease progression.

Central nervous system (CNS) infections are a significant contributor to morbidity and mortality globally. However, most published studies have been conducted in developed countries where the epidemiology and aetiology differ significantly from less developed areas. Additionally, there may be regional differences due to variation in the socio-economic levels, public health services and vaccination policies. Currently, no prospective studies have been conducted in Sabah, East Malaysia to define the epidemiology and aetiology of CNS infections. A better understanding of these is essential for the development of local guidelines for diagnosis and management.

We conducted a prospective observational cohort study in patients aged 12 years and older with suspected central nervous system infections at Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia between February 2012 and March 2013. Cerebrospinal fluid was sent for microscopy, biochemistry, bacterial and mycobacterial cultures, Mycobacterium tuberculosis polymerase chain reaction (PCR), and multiplex and MassCode PCR for various viral and bacterial pathogens.

A total of 84 patients with clinically suspected meningitis and encephalitis were enrolled. An aetiological agent was confirmed in 37/84 (44 %) of the patients. The most common diagnoses were tuberculous meningitis (TBM) (41/84, 48.8 %) and cryptococcal meningoencephalitis (14/84, 16.6 %). Mycobacterium tuberculosis was confirmed in 13/41 (31.7 %) clinically diagnosed TBM patients by cerebrospinal fluid PCR or culture. The acute case fatality rate during hospital admission was 16/84 (19 %) in all patients, 4/43 (9 %) in non-TBM, and 12/41 (29 %) in TBM patients respectively (p = 0.02).

TBM is the most common cause of CNS infection in patients aged 12 years or older in Kota Kinabalu, Sabah, Malaysia and is associated with high mortality and morbidity. Further studies are required to improve the management and outcome of TBM.

Tuberculous meningitis (TBM) is not the most common but the most serious clinical form of extrapulmonary tuberculosis. Serious complications resulting from difficulties in diagnosis and treatment of the disease makes it an important health problem. In our study, 82 patients with TBM, followed up in our clinic between January 1998-December 2002, are evaluated with their clinical and laboratory properties. 52% of our patients were females, 48% were males and their ages ranged from 15 to 70 with a mean of 32 years. The diagnosis was based on patients' history, clinical and laboratory properties, cerebrospinal fluid (CSF) findings and radiographic findings. 59% of our patients were grade II clinically, 29% were grade I, and 23% were grade III. Mostly observed complaints were headache (87%) and nausea-vomiting (63%) and fever (45%) and mostly seen physical findings were stiff neck (70%), alterations in consciousness (57%). Pleocytosis in CSF was detected in 94%, low CSF glucose level in 87%, and elevated CSF protein level in 82% of the patients. From CSF samples of 40 patients, out of total 82, Mycobacterium tuberculosis was isolated on Loewenstein-Jensen medium (49%). Nineteen patients had tuberculomas, 13 had basal meningitis, and 11 had hydrocephalus on cranial radiographic studies. 28% had miliary pattern and 26% had active infiltration and cavities on chest roentgenogram. A four-drug antituberculous regimen was administered for 88% of the patients and dexamethasone treatment was administered for 75%; 56 (68.3%) patients recovered from the illness, 14 (17%) patients had slight and 4 (4.9%) patients had serious neurological sequeales and 8 (9.8%) patients died in spite of tuberculous therapy. As a conclusion, TBM is an infectious disease with high morbidity and mortality rates. Various prognosis patterns may be observed according to the clinical grade of the patient on application. When suspected, an early diagnosis and early treatment of the disease are the most important factors which effect complication and mortality rates.

CD43, a surface glycoprotein, regulates Mycobacterium tuberculosis macrophage binding, replication, and proinflammatory cytokine induction in a murine model. We hypothesized that single-nucleotide polymorphisms (SNPs) in the CD43 gene region are associated with human tuberculosis (TB) susceptibility. We performed a case-population study in discovery (352 TB cases and 382 control subjects) and validation cohorts (339 TB cases and 376 control subjects). We examined whether 11 haplotype-tagging SNPs in the CD43 gene region were associated with tuberculous meningitis (TBM) and pulmonary TB (PTB) in Vietnam. Three SNPs from the CD43 gene region were associated with TB susceptibility with a genotypic model. The association fit a recessive genetic model and was greater for TBM than for PTB (for TBM: rs4788172, odds ratio [OR], 1.64; 95% confidence interval [CI], 1.04-2.59, rs17842268 [OR, 2.20; 95% CI, 1.29-3.76, and rs12596308 [OR, 2.38; 95% CI, 1.47-3.89]). Among TBM cases, rs17842268 was associated with decreased survival (hazard ratio, 2.7; 95% CI, 1.1-6.5; P = 0.011). In addition, rs12596308 and rs17842268 were associated with focal neurologic deficit at TBM presentation. Our data suggest that CD43 polymorphisms are associated with TB susceptibility, disease manifestations, and worse outcomes. To our knowledge, this is the first report that links CD43 genetic variants with susceptibility and outcome from a disease.

A retrospective study was made of the correlation between culture of Mycobacterium tuberculosis and detection of IgG antibody to M. tuberculosis antigen-5 in cerebrospinal fluid (CSF) by means of an enzyme linked immunosorbent assay (ELISA). Mycobacterium tuberculosis was cultured from the CSF in 14 of 70 patients with a clinical diagnosis of tuberculous meningitis (TBM). IgG antibody to M. tuberculosis antigen-5 was demonstrated in significant titres (80-640) in all 14 culture-positive patients. Thus, positive correlation was observed between culture of M. tuberculosis and detection of IgG antibody in the CSF. As a result of this observation, the CSF from 56 culture-negative patients with a clinical diagnosis TBM was specifically investigated for the detection of IgG antibody to M. tuberculosis antigen-5 and the findings were correlated with those of culture-positive patients. The assay was positive in 34 of 56 patients, the antibody titre ranging between 80 and 640. In the CSF of 70 patients with non-tuberculous neurological diseases, the assay was negative at a dilution of 1 in 80. Thus, detection of IgG antibody to M. tuberculosis antigen-5 by indirect ELISA carried 100% specificity and 60.7% sensitivity for a tuberculous aetiology in culture-negative patients with TBM. The results of this study suggest that indirect ELISA for IgG antibody to M. tuberculosis antigen-5 in CSF holds definite promise in diagnosis of TBM, particularly when repeated cultures of CSF are negative for M. tuberculosis.

<AbstractText>The use of transoral robotic surgery (TORS) and laser microsurgery (TLM) in the diagnosis and identification of the site of the unknown primary has become increasingly common. This systematic review and meta-analysis aims to assess the use and efficacy of TORS and TLM for this indication.</AbstractText><AbstractText>Systematic review and meta-analysis of studies employing TORS or TLM in diagnosis of the unknown primary tumor site in patients with cervical nodal metastases of squamous cell origin. MEDLINE, EMBASE and CINHAL were searched from inception to July 2018 for all studies that used TORS and or TLM in identifying the unknown primary.</AbstractText><AbstractText>251 studies were identified, of which 21 were eligible for inclusion. The primary tumour was identified by TORS/TLM in 78% of patients (433 out of 556). Tongue base mucosectomy (<em>TBM</em>) identified the primary in 222 of 427 cases (53%). In patients with negative physical examination, diagnostic imaging and PETCT, <em>TBM</em> identified the primary in 64% (95% CI 50, 79) cases. In patients who had negative CT/MRI imaging, negative PETCT and negative EUA and tonsillectomy, <em>TBM</em> identified a tongue base primary in 78% (95% CI 41, 92) cases. Haemorrhage, the commonest complication, was reported in 4.9% cases. Mean length of stay varied between 1.4 and 6.3 days.</AbstractText><AbstractText>Tongue base mucosectomy, performed by TORS or TLM, is highly efficacious in identifying the unknown primary in the head and neck region.</AbstractText>

BACKGROUND

The cytochrome P450 (CYP) superfamily enables terrestrial plants to adapt to harsh environments. CYPs are key enzymes involved in a wide range of metabolic pathways. It is particularly useful to be able to analyse the three-dimensional (3D) structure when investigating the interactions between CYPs and their substrates. However, only two plant CYP structures have been resolved. In addition, no currently available databases contain structural information on plant CYPs and ligands. Fortunately, the 3D structure of CYPs is highly conserved and this has made it possible to obtain structural information from template-based modelling (TBM).

METHODS

The CYP Structure Interface (CYPSI) is a platform for CYP studies. CYPSI integrated the 3D structures for 266 A. thaliana CYPs predicted by three TBM methods: BMCD, which we developed specifically for CYP TBM; and two well-known web-servers, MUSTER and I-TASSER. After careful template selection and optimization, the models built by BMCD were accurate enough for practical application, which we demonstrated using a docking example aimed at searching for the CYPs responsible for ABA 8'-hydroxylation. CYPSI also provides extensive resources for A. thaliana CYP structure and function studies, including 400 PDB entries for solved CYPs, 48 metabolic pathways associated with A. thaliana CYPs, 232 reported CYP ligands and 18 A. thaliana CYPs docked with ligands (61 complexes in total). In addition, CYPSI also includes the ability to search for similar sequences and chemicals.

CONCLUSIONS

CYPSI provides comprehensive structure and function information for A. thaliana CYPs, which should facilitate investigations into the interactions between CYPs and their substrates. CYPSI has a user-friendly interface, which is available at http://bioinfo.cau.edu.cn/CYPSI.

We present a novel persistent homological sparse network analysis framework for characterizing white matter abnormalities in tensor-based morphometry (TBM) in magnetic resonance imaging (MRI). Traditionally TBM is used in quantifying tissue volume change in each voxel in a massive univariate fashion. However, this obvious approach cannot be used in testing, for instance, if the change in one voxel is related to other voxels. To address this limitation of univariate-TBM, we propose a new persistent homological approach to testing more complex relational hypotheses across brain regions. The proposed methods are applied to characterize abnormal white matter in maltreated children. The results are further validated using fractional anisotropy (FA) values in diffusion tensor imaging (DTI).

Central nervous system tuberculosis (TB) is devastating and affects vulnerable populations. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculous meningitis (TBM) specifically are nearly uniformly fatal, with little information being available to guide the treatment of these patients. Delamanid (DLM), a nitro-dihydro-imidazooxazole, is a new, well-tolerated anti-TB drug with a low MIC (1 to 12 ng/ml) against Mycobacterium tuberculosis It is used for the treatment of pulmonary MDR-TB, but pharmacokinetic (PK) data for DLM in the central nervous system (CNS) of patients with TBM are not available. In the present study, we measured DLM concentrations in the brain and cerebrospinal fluid (CSF) of six rabbits with and without experimentally induced TBM receiving single-dose DLM. We report the steady-state CSF concentrations from three patients receiving DLM as part of multidrug treatment who underwent therapeutic drug monitoring. Drug was quantified using liquid chromatography-tandem mass spectrometry. In rabbits and humans, mean concentrations in CSF (in rabbits, 1.26 ng/ml at 9 h and 0.47 ng/ml at 24 h; in humans, 48 ng/ml at 4 h) were significantly lower than those in plasma (in rabbits, 124 ng/ml at 9 h and 14.5 ng/ml at 24 h; in humans, 726 ng/ml at 4 h), but the estimated free CSF/plasma ratios were generally >1. In rabbits, DLM concentrations in the brain were 5-fold higher than those in plasma (means, 518 ng/ml at 9 h and 74.0 ng/ml at 24 h). All patients with XDR-TBM receiving DLM experienced clinical improvement and survival. Collectively, these results suggest that DLM achieves adequate concentrations in brain tissue. Despite relatively low total CSF drug levels, free drug may be sufficient and DLM may have a role in treating TBM. More studies are needed to develop a fuller understanding of its distribution over time with treatment and clinical effectiveness.

Overproduction of extracellular matrix (ECM) is considered to be primarily responsible for both glomerular and tubulointerstitial (TI) changes in diabetic nephropathy (DN). To clarify the possible role of the collagens in TI damage in DN, type III interstitial collagen and type IV basement membrane collagen were studied in 10 cases of DN and 10 control cases by immunohistochemistry and in situ hybridization techniques. In control cases, no immunostaining for type III collagen was found in the renal tubules, while strongly positive in the adjacent interstitium. On the other hand, type IV collagen was found weakly in the tubular basement membrane (TBM) in control cases. In DN, increased immunostaining for both type III and type IV collagens were found in the damaged tubulointenstitium (TI). To determine the sources of these collagens in TI damage, non-radioactive in situ hybridization was performed utilizing thymine-thymine (T-T) dimerized synthetic oligonucleotides complementary to either human pro alpha 1 (III) chain or pro alpha 1 (IV) chain mRNA as probe. In normal tubules, tubular epithelial cells were not uniformly but persistently positive for pro alpha 1 (IV) mRNA. Meanwhile, no specifically detectable positive hybridization signals for pro alpha 1 (III) mRNA was found in the normal tubular epithelial cells. Accelerated synthesis of both type III and type IV collagens by tubular epithelial cells was noted in TI damage in DN. From the results we concluded that excessive synthesis of both type III and type IV collagens by tubular epithelial cells might significantly contribute to the TI damage found in DN.

Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB), and key TB antimicrobials, including rifampin, have restricted brain penetration. A lack of reliable data on intralesional drug biodistribution in infected tissues has limited pharmacokinetic (PK) modeling efforts to optimize TBM treatments. Current methods to measure intralesional drug distribution rely on tissue resection, which is difficult in humans and generally limited to a single time point even in animals. In this study, we developed a multidrug treatment model in rabbits with experimentally induced TBM and performed serial noninvasive dynamic ¹¹C-rifampin positron emission tomography (PET) over 6 weeks. Area under the curve brain/plasma ratios were calculated using PET and correlated with postmortem mass spectrometry. We demonstrate that rifampin penetration into infected brain lesions is limited, spatially heterogeneous, and decreases rapidly as early as 2 weeks into treatment. Moreover, rifampin concentrations in the cerebrospinal fluid did not correlate well with those in the brain lesions. First-in-human ¹¹C-rifampin PET performed in a patient with TBM confirmed these findings. PK modeling predicted that rifampin doses (≥30 mg/kg) were required to achieve adequate intralesional concentrations in young children with TBM. These data demonstrate the proof of concept of PET as a clinically translatable tool to noninvasively measure intralesional antimicrobial distribution in infected tissues.

BACKGROUND

Hyponatremia has long been recognized as a potentially serious metabolic consequence of tuberculous meningitis (TBM) occurring in 35-65% of children with the disease. The syndrome of inappropriate antidiuretic hormone (SIADH) secretion has for long been believed to be responsible for the majority of cases of hyponatremia in TBM. Cerebral salt wasting syndrome (CSWS) is being increasingly reported as a cause of hyponatremia in some of these children.

OBJECTIVE

This study was done to determine the frequency and causes of hyponatremia in children with TBM.

METHODS

Children with newly diagnosed TBM admitted over a 2-year period (January 2009 to December 2010) were included. All patients received anti-tubercular therapy, mannitol for cerebral edema, and steroids. Patients were monitored for body weight, urine output, signs of dehydration, serum electrolytes, blood urea nitrogen, serum creatinine, and urinary sodium. Hyponatremia was diagnosed if the serum sodium was <135 mEq/L. CSWS was diagnosed if there was evidence of excessive urine output, volume depletion, and natriuresis in the presence of hyponatremia. The outcome in terms of survival or death was recorded.

RESULTS

Twenty-nine of 75 children (38.7%) with TBM developed hyponatremia during their hospital stay. In 19 patients, hyponatremia subsided after the discontinuation of mannitol. Ten patients with persistent hyponatremia had CSWS. There were no patients with SIADH.

CONCLUSIONS

CSWS is an important cause of hyponatremia in children with newly diagnosed TBM. In our patients, it was more commonly seen than SIADH.

BACKGROUND

Discrimination between tuberculous and acute bacterial meningitis is difficult by clinical features alone and laboratory methods may only supplement the clinical suspicion. We aimed to validate the diagnostic criteria by Thwaites et al. [1] and construct our own diagnostic predictors based on the clinical and laboratory features.

METHODS

380 patients of acute bacterial meningitis (ABM) and 210 patients of tuberculous meningitis (TBM) were enrolled retrospectively from June 2004 to June 2007 and prospectively from July 2007 to September 2008. HIV positive patients were excluded. Detailed history, clinical examination CSF analysis, haematological, biochemical investigations and imaging was performed in all patients.

RESULTS

Factors associated with the diagnosis of TBM in the present study included rural area of residence, longer duration of disease, presence of clear CSF, lower percentage of CSF neutrophils, presence of diplopia and hemiparesis. On validation, age did not appear as a significant factor in our population. The diagnostic algorithm from our study group had a sensitivity of 95.71% and specificity of 97.63%.

CONCLUSIONS

The diagnostic criterion has a fair validation in our population when the age factor is excluded. The rule is useful in HIV negative patients with low CSF sugar and negative organism yield in the CSF.

HR-pQCT enables in vivo multi-parametric assessments of bone microstructure in the distal radius and distal tibia. Conventional HR-pQCT image analysis approaches summarize bone parameters into global scalars, discarding relevant spatial information. In this work, we demonstrate the feasibility and reliability of statistical parametric mapping (SPM) techniques for HR-pQCT studies, which enable population-based local comparisons of bone properties. We present voxel-based morphometry (VBM) to assess trabecular and cortical bone voxel-based features, and a surface-based framework to assess cortical bone features both in cross-sectional and longitudinal studies. In addition, we present tensor-based morphometry (TBM) to assess trabecular and cortical bone structural changes. The SPM techniques were evaluated based on scan-rescan HR-pQCT acquisitions with repositioning of the distal radius and distal tibia of 30 subjects. For VBM and surface-based SPM purposes, all scans were spatially normalized to common radial and tibial templates, while for TBM purposes, rescans (follow-up) were spatially normalized to their corresponding scans (baseline). VBM was evaluated based on maps of local bone volume fraction (BV/TV), homogenized volumetric bone mineral density (vBMD), and homogenized strain energy density (SED) derived from micro-finite element analysis; while the cortical bone framework was evaluated based on surface maps of cortical bone thickness, vBMD, and SED. Voxel-wise and vertex-wise comparisons of bone features were done between the groups of baseline and follow-up scans. TBM was evaluated based on mean square errors of determinants of Jacobians at baseline bone voxels. In both anatomical sites, voxel- and vertex-wise uni- and multi-parametric comparisons yielded non-significant differences, and TBM showed no artefactual bone loss or apposition. The presented SPM techniques demonstrated robust specificity thus warranting their application in future clinical HR-pQCT studies.

The incidence of cryptococcal meningitis (CM) and tuberculous meningitis (TBM) have gradually increased in recent years. These two types of meningitis are easily misdiagnosed which leads to a poor prognosis. In this study we compared differences of clinical features and prognostic factors in non-HIV adults with CM and TBM.

We retrospectively reviewed the medical records of CM and TBM patients from January 2008 to December 2015 in our university hospital in China. The data included demographic characteristics, laboratory results, imaging findings, clinical outcomes.

A total of 126 CM and 105 TBM patients were included. CM patients were more likely to present with headache, abnormal vision and hearing, and they might be less prone to fever and cough than TBM patients (P < 0.05). Higher percentage of CM patients presented with cerebral ischemia/infarction and demyelination in brain MRI than TBM patients (P < 0.05). CM patients had lower counts of WBC in CSF, lower total protein in CSF and serum CD4/CD8 ratio than TBM patients (P < 0.05). After three months of treatment, CM group have worse outcome than TBM group (P < 0.05). Multivariate analysis showed that age more than 60y (OR = 4.981, 95% CI: 1.955-12.692, P = 0.001), altered mentation (OR = 5.054, 95% CI: 1.592-16.046, P = 0.006), CD4/CD8 ratios < 1 (OR = 8.782, 95% CI: 2.436-31.661, P = 0.001) and CSF CrAg ≥ 1:1024 (OR = 4.853, 95% CI: 1.377-17.098, P = 0.014) were independent risk factors for poor prognosis for CM patients. For TBM patients, hydrocephalus (OR = 7.290, 95% CI: 1.630-32.606, P = 0.009) and no less than three underlying diseases (OR = 6.899, 95% CI: 1.766-26.949, P = 0.005) were independent risk factors, headache was a protective factor of prognosis.

Our study provided some helpful clues in the differential diagnosis of non-HIV patients with CM or TBM and identified some risk factors for the poor prognosis of these two meningitis which could help to improve the treatment outcome. Further studies are worth to be done.