Longitudinal voxel-based morphometry studies have demonstrated morphological changes in cortical structures following motor and cognitive learning. In this study, we applied, for the first time, tensor-based morphometry (TBM) to assess the short-term structural brain gray matter (GM) changes associated with cognitive learning in healthy subjects. Using a 3 T scanner, a 3D T1-weighted sequence was acquired from 32 students at baseline and after two weeks. Students were separated into two groups: 13 defined as "students in cognitive training", who underwent a two-week cognitive learning period, and 19 "students not in cognitive training", who were not involved in any teaching activity. GM changes were assessed using TBM and statistical parametric mapping. Baseline regional GM volume did not differ between the two groups. At follow up, compared to "students not in cognitive training", the "students in cognitive training" had a significant GM volume increase in the dorsomedial frontal cortex, the orbitofrontal cortex, and the precuneus (p<0.001). These results suggest that cognitive learning results in short-term structural GM changes of neuronal networks of the human brain, which are known to be involved in cognition. This may have important implications for the development of rehabilitation strategies in patients with neurological diseases.

Tensor-based morphometry (TBM) is widely used in computational anatomy as a means to understand shape variation between structural brain images. A 3D nonlinear registration technique is typically used to align all brain images to a common neuroanatomical template, and the deformation fields are analyzed statistically to identify group differences in anatomy. However, the differences are usually computed solely from the determinants of the Jacobian matrices that are associated with the deformation fields computed by the registration procedure. Thus, much of the information contained within those matrices gets thrown out in the process. Only the magnitude of the expansions or contractions is examined, while the anisotropy and directional components of the changes are ignored. Here we remedy this problem by computing multivariate shape change statistics using the strain matrices. As the latter do not form a vector space, means and covariances are computed on the manifold of positive-definite matrices to which they belong. We study the brain morphology of 26 HIV/AIDS patients and 14 matched healthy control subjects using our method. The images are registered using a high-dimensional 3D fluid registration algorithm, which optimizes the Jensen-Rényi divergence, an information-theoretic measure of image correspondence. The anisotropy of the deformation is then computed. We apply a manifold version of Hotelling's T2 test to the strain matrices. Our results complement those found from the determinants of the Jacobians alone and provide greater power in detecting group differences in brain structure.

BACKGROUND

Cerebrospinal fluid diversion procedures are indicated in patients with hydrocephalus after tuberculous meningitis (TBM). We present 2 patients with hydrocephalus after TBM who were successfully treated with endoscopic third ventriculostomy (ETV).

METHODS

Two patients had been diagnosed with hydrocephalus after TBM and had undergone ventriculoperitoneal shunt surgery for the same. They presented with multiple episodes of shunt dysfunction. Endoscopic third ventriculostomy was performed (twice for one patient), and the patients were evaluated clinically and radiologically after the procedure.

RESULTS

On long-term clinical follow-up (3 and 2 years, respectively), both patients were asymptomatic after the ETV. The first patient was radiologically evaluated 7 months after the procedure and the second patient 2 years after the procedure. The first patient showed a decrease in ventricular size. The second patient did not show any significant change in the ventricular size.

CONCLUSIONS

Endoscopic third ventriculostomy can be considered as a safe and long-lasting solution for hydrocephalus after chronic TBM.

OBJECTIVE

To determine whether long-term course of treated major depression has an effect on the structure of the brain and the hippocampal volume.

METHODS

An 11-year follow-up procedure was used with data collection at baseline and again at follow-up. Tensor-based morphometry (TBM) and automatic hippocampal volume measure was performed on different datasets. The baseline dataset consisted of T1-weighted magnetic resonance images (MRIs) of 24 in-patients suffering from major depression and 33 healthy controls. The second dataset consisted of T1-weighted MRIs of 31 remitted depressive patients and 36 healthy controls. The longitudinal dataset consisted of 19 patients and 19 matched healthy controls present at both the first and the second dataset. Brain segmentation and hippocampal segmentation were fully automated and were based on a spatial normalization to the International Consortium of Brain Mapping (ICBM) non-linear model.

RESULTS

Depressed patients were found to have smaller temporal lobes bilaterally, medulla and right hippocampus at baseline. However, these changes were not found at follow-up 11 years later. Moreover, these changes did not significantly correlate with the illness outcome.

CONCLUSIONS

Brain structure changes seem to be state dependent in major depression, only occurring in acute episode of major depression and normalizing after remission.

Neuropathological studies have demonstrated decreased Purkinje cells in cerebellar cortex and changes in the dentate nucleus of the cerebellum, the projection target for the Purkinje cells, in autistic spectrum disorders (ASD). The dentatorubrothalamic tract is formed by efferents from the dentate nucleus projecting toward the red nucleus with axon collaterals to this nucleus and continuing to innervate the ventral lateral and ventral anterior nuclei of the thalamus. In the current study, we assessed whether the dentatorubrothalamic tract is altered in ASD using Q-ball imaging (QBI). The QBI tractography was performed in 13 children with high functioning ASD (HFA), 11 children with low functioning ASD (LFA), and 14 typically developing children (TD). Regions of interest in dentate nucleus and red nucleus in both hemispheres were objectively placed to sort bilateral dorsal-rostral (DR), dorsal-caudal (DC), ventral-rostral (VR), and ventral-caudal (VC) portions of the dentatorubrothalamic pathway. Group differences in fractional anisotropy (FA), axial diffusivity, radial diffusivity, and fiber volume of individual pathways were analyzed. Significantly reduced FA was found in children with LFA and HFA, compared to the TD group in tracts originating in all four subdivisions of the right dentate nucleus. Tract-based morphometry (TBM) analysis demonstrated significant reductions of FA in caudal midbrain (p<0.0001), dorsal-caudal dentate (p=0.0013), and ventral-caudal dentate (p=0.0061) on the right in the LFA group. The FA values in TBM segments of right VR and VC pathways were significantly correlated with communication skills in the combined HFA/LFA group, while there was a significant correlation found between TBM segments of right DR pathway and daily living skills (r=0.76; p=0.004). Decreased white matter integrity in dorsal portions of the dentatorubrothalamic tract may be related to motor features in ASD, while changes in the ventral portions are related more to communication behavior.

BACKGROUND

In interstitial fibrosis, monocytes and myofibroblasts have been directly implicated in scarring, apoptosis, and tissue necrosis. While much has been done to explore the role of these cell types individually in fibrosis, the interactive dependency of monocytes and myofibroblasts has been only marginally explored.

METHODS

Alport mice were treated or not with a soluble receptor inhibitor for transforming growth factor-beta 1 (TGF-beta 1), which was previously shown to inhibit the accumulation of myofibroblasts, but not monocytes, in the tubulointerstitium. Kidneys were examined for fibrosis using several matrix markers, TGF-beta 1 mRNA expression by in situ hybridization, apoptosis using the terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL) assay, expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPS) by dual immunofluorescence microscopy, MMP activity by gelatin and in situ zymography, MMP mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR), and basement membrane degradation by dual immunofluorescence confocal microscopy and electron microscopy.

RESULTS

Treated mice showed a markedly reduced accumulation of matrix proteins. Tissue monocytes express TGF-beta 1 mRNA, and TGF-beta 1 is required for myofibroblast accumulation. The number of apoptotic cells was not influenced by TGF-beta 1 inhibition. Monocytes express MMP-2, MMP-9, TIMP-2, and TIMP-3. MMP activity and mRNA expression is equally up regulated in treated and untreated Alport mice. Tubular basement membranes (TBM) around clusters of monocytes are notably degraded. TGF-beta 1 inhibition does not extend the life of Alport mice.

CONCLUSIONS

These studies demonstrate that monocytes may influence myofibroblast accumulation via TGF-beta1, and that monocytes, and not myofibroblasts, are associated with tubular atrophy in Alport mice. Elevated MMP expression and activity is associated with TBM destruction near monocytes clusters, suggesting an anoikis mechanism may contribute to apoptosis in this model.

OBJECTIVE

This review summarizes the literature on adult or acquired tracheobronchomalacia (TBM) and explores its association with chronic obstructive pulmonary disease (COPD).

RESULTS

Dynamic imaging of central airways, a noninvasive test as effective as bronchoscopy to diagnose TBM, has increased the recognition of this disorder. Airway stabilization techniques using stents placed via bronchoscopy have also furthered the interest in TBM. The association of TBM with COPD is of growing interest particularly in the face of worldwide rise in COPD incidence. The pathobiology behind this condition may share significant common ground with COPD.

CONCLUSIONS

Despite the lack of uniformly accepted diagnostic criteria and the uncertain correlation to clinical manifestations and course, technologic advances in imaging and interventional bronchoscopy have spurred clinicians' interest in TBM. In exploring the association of TBM and COPD, an intriguing consideration is whether TBM could be an extension of peripheral airway disease.

The relationship between autoantibody reactivities and nephritis in systemic lupus erythematosus (SLE) is unclear. We studied MRL/l mice which developed a considerable albuminuria (either mice with short ( < 1 week) or heavy and prolonged (3 weeks) albuminuria) and compared them with non-albuminuric age-matched controls, with young (12 weeks old) non-albuminuric mice and with mice which were followed for 36 weeks and did not develop albuminuria. In a longitudinal prospective study on plasma samples we correlated a variety of anti-nuclear reactivities and reactivities against extracellular matrix (ECM) components, with the onset of albuminuria. We found that at the onset of albuminuria, anti-DNA was higher while anti-nucleosome and anti-H2A/H2B-DNA subnucleosome reactivities were lower compared with age-matched non-albuminuric mice. We also studied glomerular eluates of these mice in ELISA and in indirect immunofluorescence (IF). In the eluates we found with IF that anti-glomerular basement membrane (GBM)-tubular basement membrane (TBM) antibodies were already present in 12-week-old non-albuminuric mice. These eluates showed no anti-nuclear antibodies. In eluates of albuminuric mice more immunoglobulin was deposited, and anti-ECM, anti-DNA and anti-nucleosome reactivities were higher than in eluates of age-matched non-albuminuric mice. The deposition of anti-nucleosome antibodies preceded the deposition of anti-DNA antibodies since they were deposited to a greater extent in mice with a short albuminuria. We conclude that anti-GBM-TBM antibodies are the first autoantibodies that deposit in glomeruli of MRL/l mice at an early age. The onset of albuminuria is associated with additional deposition of both anti-ECM and anti-nuclear (anti-nucleosome and anti-DNA) antibodies, but the difference with non-albuminuric mice seems to be more quantitative than qualitative.

BACKGROUND

Prognostic indicators for tuberculous meningitis (TBM) offer realistic expectations for parents of affected children. Infarctions affecting the basal ganglia are associated with a poor outcome.

OBJECTIVE

To correlate the distribution of infarction in children with TBM on CT with an outcome score (OS).

METHODS

CT brain scans in children with TBM were retrospectively reviewed and the distribution of infarctions recorded. The degree of correlation with OS at 6 months was determined.

RESULTS

There was a statistically significant association between all sites of infarction (P = 0.0001-0.001), other than hemispheric (P = 0.35), and outcome score. There was also a statistically significant association between all types of infarction (P = 0.0001-0.02), other than hemispheric (P = 0.05), and overall poor outcome. The odds ratio for poor outcome with bilateral basal ganglia and internal capsule infarction was 12. The odds ratio for poor outcome with 'any infarction' was 4.91 (CI 2.24-10.74), with 'bilateral infarctions' 8.50 (CI 2.49-28.59), with basal ganglia infarction 5.73 (CI 2.60-12.64), and for hemispheric infarction 2.30 (CI 1.00-5.28).

CONCLUSIONS

Infarction is associated with a poor outcome unless purely hemispheric. MRI diffusion-weighted imaging was not part of this study, but is likely to play a central role in detecting infarctions not demonstrated by CT.

Magnetic resonance imaging (MRI) was performed in cocaine-dependent subjects to determine the structural changes in brain compared to non-drug using controls. Cocaine-dependent subjects and controls were carefully screened to rule out brain pathology of undetermined origin. Magnetic resonance images were analyzed using tensor-based morphometry (TBM) and voxel-based morphometry (VBM) without and with modulation to adjust for volume changes during normalization. For TBM analysis, unbiased atlases were generated using two different inverse consistent and diffeomorphic nonlinear registration techniques. Two different control groups were used for generating unbiased atlases. Independent of the nonlinear registration technique and normal cohorts used for creating the unbiased atlases, our analysis failed to detect any statistically significant effect of cocaine on brain volumes. These results show that cocaine-dependent subjects do not show differences in regional brain volumes compared to non-drug using controls.

Transcriptional regulation in eukaryotes is thought to occur through interactions between specific transcription factors and the general transcription machinery. We show that the regulatory protein FosB, but not FosB/SF or Fra-1, specifically and stably associates with the TATA box binding protein (TBP) and the multiprotein complex TFIID. The binding to TBP is specified by the last 55 C-terminal amino acids of FosB, requiring a small amino acid sequence, termed the 'TBP binding motif' (TBM). Deletion of the TBM affects transcriptional activity slightly, but it is adjacent to a proline-rich sequence which constitutes the major transactivation domain. However, both regions are required for the transformation of Rat-1A cells by FosB. Transfection experiments demonstrate that inhibition of transactivation due to excess levels of Gal4-FosB (squelching) can be partially relieved by the co-expression of TBP, which establishes that TFIID is a functional target of FosB. Since TBP binding is not exhibited by FosB/SF or Fra-1, we suggest that the activity mediated by the TBP interaction is one differentiating characteristic that distinguishes the FosB functions from those of FosB/SF and Fra-1.

We studied the expression of laminin chains in embryonic and adult human kidney by indirect immunofluorescence with monoclonal antibodies (MAbs). In embryonic human kidney, immunoreactivity for laminin alpha 1, beta 1, and gamma 1 chains was found in basement membranes (BMs) of primary vesicles, in comma- and S-shaped bodies, and in more mature stages of glomeruli and in tubules. The beta 2 chain of laminin was absent in the early glomerular structures but was prominent in BMs of maturing glomeruli (GBMs) and Bowman's capsule (BCBMs) and was also detectable in some tubules. Both the beta 2 and alpha 2 chains were variably seen in medullary tubule BMs. In adult human kidney, laminin alpha 1 chain was seen in GBMs and all tubule BMs (TBMs) as well as in arterial smooth muscle BMs (SMBMs). Laminin beta 1 chain reactivity was found in all TBMs, but not in GBMs or SMBMs. In the glomerulus, a distinct mesangial type of reaction was revealed with the MAbs to beta 1 and alpha 2 chains. The GBMs and SMBMs reacted with MAbs to the beta 2 chain, but reactivity was lacking in BCBMs. Laminin gamma 1 chain immunoreactivity was weakly present in BCBMs, GBMs, and SMBMs. The alpha 3 and beta 3 chains could not be detected in developing or adult human nephron. The results show that during development the BMs in human nephron undergo distinct changes, laminin beta 1 chain being transiently co-expressed with alpha 1 chain during early glomerular development and then becoming replaced by the beta 2 chain, which, on the other hand, disappears from the BCBMs on maturation. The alpha 2 chain appears to emerge in the mesangium late during development.

Immunohistological and elution studies of the human placenta revealed the presence of IgG on the trophoblastic basement membrane (TBM) which demonstrated specificity for placental but not lung, thyroid, or kidney basement membranes, suggesting the presence of a placenta-specific antigen in TBM. IgG comprised the bulk of immunoglobulin in eluates, and small amounts of IgA, trace amounts of IgM, but no IgE or IgD were identified in eluates. The distribution of IgG subclasses in eluate was not unusual as compared to maternal and neonatal sera, and Gm and Inv typing of eluates indicated that it was of maternal origin. Small amounts of eluate-IgG effectively inhibited the blastogenic response of unrelated lymphocytes to old tuberculin, phytohemagglutinin, and in one- or two-way mixed lymphocyte culture reactions. The inhibition was distinct from nonspecific inhibitors, and dose-response analysis indicated that eluate was very much more potent as an inhibitor than were the nonspecific inhibitors. Inhibition was shown to not be due to anti-HL-A activity, and was probably not due to aggregated IgG or immune complexes. Binding of eluate to lymphocytes was very loose as shown by washing experiments, and no binding could be shown by immunofluorescence. The capacity of eluate IgG to inhibit MLC was retained after pepsin digestion to F(ab')(2), suggesting that the inhibition reactions were immunological. It is suggested that eluate-IgG is maternal blocking antibody to a hitherto uncharacterized trophoblast antigen, and it is speculated that either abnormal antigen or aberrant responses to antigen could result in fetal wastage.

BACKGROUND

We report our preliminary experience with two cases of tuberculous meningitis (TBM) in which endoscopic third ventriculostomy (ETV) was performed to treat non-communicating hydrocephalus. For many years, the insertion of ventriculoperitoneal shunts has been the standard treatment for hydrocephalus in patients with TBM, although the indications for and timing of surgery are not uniformly accepted. Shunt insertion is associated with a high incidence of complications, particularly with long-term follow-up. An alternative treatment for hydrocephalus in this group of patients would clearly be of great benefit. The indications for ETV have increased in the last decade, and there are reports of some effectiveness of the procedure in patients with hydrocephalus due to bacterial meningitis. To our knowledge, ETV has not been described in the management of TBM.

METHODS

We report the early results of our preliminary experience with ETV in two patients who presented with neurological compromise due to hydrocephalus and raised intracranial pressure. The clinical context and pre-operative investigation of these patients are presented. The emphasis is placed on the distinction between communicating and non-communicating pathologies as a guide to management options. We detail our surgical findings and the peculiar endoscopic challenges that the condition presented to us. Follow-up in these patients included clinical and investigational data suggesting early effectiveness of the procedure in converting non-communicating hydrocephalus into a communicating one, which can then be treated medically.

CONCLUSIONS

Endoscopic third ventriculostomy is presented as a new application of a procedure accepted for other indications in the treatment of non-communicating hydrocephalus. There are particular aspects of the use of this procedure related to the unique pathology of TBM that are significantly different. We explain our rationale for endoscopy in these patients, and suggest a protocol in which endoscopy may play a role in the management of patients with raised intracranial pressure due to tuberculous hydrocephalus.

MR imaging was performed on 27 children with stage II-III tuberculous meningitis for the specific purpose of examining the brainstem, as well as comparison with other CT features of the disease. In addition to defining the ischemic disturbances of basal ganglia and diencephalon more clearly, MR also demonstrates the frequent occurrence of parenchymal signal abnormalities in the brainstem and adjacent temporal lobes, which are invisible or uncertain on CT. Although the presence of brainstem abnormalities on MR correlated well with clinical findings of brainstem dysfunction, clinical staging on admission remains the best prognostic indicator in advanced TBM. We also review the MR features of basal exudation, hydrocephalus and tuberculoma.

Although some progress has been made in recent years, there are truly large gaps in our basic knowledge on how the TBM is assembled during development. Some of the new evidence presented here indicates that both the tubular epithelium and interstitial fibroblasts participate in TBM protein biosynthesis during nephrogenesis. In addition, newly assembled segments of TBM are spliced or inserted into existing TBM during tubule expansion and elongation. A similar splicing mechanism has been described previously in the GBM, endocrine organs, and intestinal villi, and this mechanism therefore probably represents a fundamental process of basement membrane formation. A major unresolved question at present, however, is how this mechanism operates at the molecular level. Does the newly formed basement membrane contain identical components as that already present? Since an enzymatic process is likely occurring in the insertion of new matrix into old, which enzymes are involved? What is the cellular origin of these enzymes and which matrix component(s) is their substrate? Even more fundamental yet unanswered questions have to do with the mechanisms of epithelial induction, basement membrane gene activation, and tubular morphogenesis. Once the basement membrane is fully formed at the completion of nephrogenesis, what controls basement membrane turnover and how does this operate? Clearly, much additional research is necessary to address these questions. This work is needed, however, before we can fully understand the important roles basement membranes play in normal development as well as in disease.

Tuberculous meningitis (TBM) is the most devastating form of meningitis and prompt diagnosis holds the key to its management. Conventional microbiology has limited utility and nucleic acid-based methods have not been widely accepted for various reasons. In view of the paucibacillary nature of cerebrospinal fluid (CSF) and the recent demonstration of free Mycobacterium tuberculosis DNA in clinical specimens, the present study was designed to evaluate the utility of CSF 'filtrates' for the diagnosis of TBM using PCR. One hundred and sixty-seven CSF samples were analysed from patients with 'suspected' TBM (n=81) and a control group including other cases of meningitis or neurological disorders (n=86). CSF 'sediments' and 'filtrates' were analysed individually for M. tuberculosis DNA by quantitative real-time PCR (qRT-PCR) and conventional PCR. Receiver-operating characteristic curves were generated from qRT-PCR data and cut-off values of 84 and 30 were selected for calling a 'filtrate' or 'sediment' sample positive, respectively. Based on these, TBM was diagnosed with 87.6% and 53.1% sensitivity (P<0.001) in 'filtrates' and 'sediments', respectively, and with 92% specificity each. Conventional devR and IS6110 PCR were also significantly more sensitive in 'filtrates' versus 'sediments' (sensitivity of 87.6% and 85.2% vs 31% and 39.5%, respectively; P<0.001). The qRT-PCR test yielded a positive likelihood ratio of 11 and 6.6 by analysing 'filtrate' and 'sediment' fractions, respectively, which establishes the superiority of the 'filtrate'-based assay over the 'sediment' assay. PCR findings were separately verified in 10 confirmed cases of TBM, where M. tuberculosis DNA was detected using devR PCR assays in 'sediment' and 'filtrate' fractions of all samples. From this study, we conclude that (i) CSF 'filtrates' contain a substantial amount of M. tuberculosis DNA and (ii) 'filtrates' and not 'sediments' are likely to reliably provide a PCR-based diagnosis in 'suspected' TBM patients.

Tracheobronchomalacia (TBM) is the most common congenital central airway anomaly, but it frequently goes unrecognized or is misdiagnosed as other respiratory conditions such as asthma. Recent advances in multidetector computed tomography (CT) have enhanced the ability to noninvasively diagnose TBM with the potential to reduce the morbidity and mortality associated with this condition. Precise indications are evolving but may include symptomatic pediatric patients with known risk factors for TBM and patients with otherwise unexplained impaired exercise tolerance; recurrent lower airways infection; and therapy-resistant, irreversible, and/or atypical asthma. With multidetector CT, radiologists can now perform objective and quantitative assessment of TBM with accuracy similar to that of bronchoscopy, the reference standard for diagnosing this condition. Multidetector CT enables a comprehensive evaluation of pediatric patients suspected of having TBM by facilitating accurate diagnosis, determining the extent and degree of disease, identifying predisposing conditions, and providing objective pre- and postoperative assessments. In this article, the authors present a step-by-step primer of multidetector CT imaging for evaluating infants and children with suspected TBM, including clinical indications, patient preparation, multidetector CT techniques and protocols, two- and three-dimensional processing of multidetector CT data, and image interpretation. The major aim of this article is to facilitate the reader's ability to successfully employ multidetector CT imaging protocols for evaluation of TBM in infants and children in daily clinical practice.

The diagnosis of tuberculous meningitis (TBM) remains a complex issue because the most widely used conventional diagnostic tools, such as culture and PCR assay for cerebrospinal fluid (CSF) samples, are unable to rapidly detect Mycobacterium tuberculosis with sufficient sensitivity in the acute phase of TBM. Based on TaqMan PCR, we designed a novel technique consisting of an internally controlled quantitative nested real-time (QNRT) PCR assay that provided a marked improvement in detection sensitivity and quantification. We applied this novel technique to quantitatively detect M. tuberculosis DNA in CSF samples from patients with suspected TBM. For use as the internal control in the measurement of the M. tuberculosis DNA copy numbers in the QNRT-PCR assay, the original mutation (M) plasmid, which included an artificial random 22-nucleotide sequence within an inserted DNA fragment of the MPB64 gene of M. tuberculosis, was prepared. The QNRT-PCR assay showed high sensitivity and specificity that were approximately equivalent to those of the conventional nested PCR assay. Moreover, the QNRT-PCR assay made it possible to precisely and quantitatively detect the initial copy number of M. tuberculosis DNA in CSF samples. Therefore, compared to the conventional PCR assay, the QNRT-PCR assay can be considered a more useful and advanced technique for the rapid and accurate diagnosis of TBM. To establish the superiority of this novel technique in TBM diagnosis, it will be necessary to accumulate data from a larger number of patients with suspected TBM.

METHODS

Intracranial tuberculomas are commonly observed neuroimaging abnormalities in tuberculous meningitis (TBM).

OBJECTIVE

to evaluate the predictors and prognostic significance of tuberculomas in patients with TBM.

METHODS

In a retrospective follow-up study, contrast-enhanced magnetic resonance imaging was performed at study inclusion and after 9 months of follow-up. Univariate analysis and multivariate analysis were used to identify predictive factors for tuberculoma. Prognosis (death and severe disability) was assessed using the modified Rankin scale.

RESULTS

At inclusion, 43 of 110 patients had cerebral tuberculomas. Seven patients developed paradoxical tuberculomas. Predictors of tuberculomas were raised cerebrospinal fluid (CSF) protein (>3 g/l) and meningeal enhancement. Multivariate analysis did not show any significant predictors. During follow-up, the only significant predictor of paradoxical development of tuberculomas was raised CSF protein (>3 g/l). After 9 months of follow-up, 32 patients had died or had severe disability. Survival analysis revealed that patients with tuberculomas and those without tuberculomas had a similar prognosis.

CONCLUSIONS

Tuberculomas occurred in approximately 39% of the patients with TBM. Significant predictors were meningeal enhancement and raised CSF protein. TBM patients with or without tuberculomas had a similar prognosis.

OBJECTIVE

Endoscopic third ventriculostomy (ETV) is increasingly being used as an alternative treatment for post-tuberculous meningitis (TBM) hydrocephalus. The aim of this study was to affirm the role of ETV in patients with TBM hydrocephalus and also to study the usefulness of cine phase-contrast MR imaging (cine MR imaging) for functional assessment of the ETV stoma. An additional goal was to identify factors that influence the outcome of ETV, so as to define patients with TBM hydrocephalus in whom ETV is warranted.

METHODS

Twenty-six patients with TBM hydrocephalus treated with ETV were evaluated clinically and with cine MR imaging postoperatively. The duration of follow-up ranged from 1 to 15 months. The authors evaluated flow void changes in the floor of the third ventricle and analyzed parameters from the preoperative data, which they then used as a basis for comparison between endoscopically successful and endoscopically unsuccessful cases.

RESULTS

The overall success rate of ETV in TBM hydrocephalus was 73.1% in this case series. Cine MR imaging showed a sensitivity of 94.73% and specificity of 71.42% for the functional assessment of third ventriculostomy in these patients, with the efficacy being maintained during follow-up. The outcome of ETV showed a statistically significant correlation with the stage of illness and presence of intraoperative cisternal exudates. Although duration of symptoms and duration of preoperative antituberculous therapy (ATT) appeared to influence the outcome, their correlation with outcome was not statistically significant.

CONCLUSIONS

Endoscopic third ventriculostomy should be considered as the first surgical option for CSF diversion (that is, before shunt surgery) in patients with TBM hydrocephalus. Cine MR imaging is a highly effective noninvasive tool for the postoperative functional assessment of stomata. Patients who presented with a history of longer duration and those who were administered preoperative ATT for a longer period had a better outcome of endoscopic treatment. Outcome was poorer in patients who presented with higher stages of illness and in those in whom cisternal exudates were observed intraoperatively.

Interstitial fibrosis and tubular basement membrane (TBM) thickening are evident within 16 days of unilateral ureteral obstruction (UUO) in the rabbit, and resemble the changes previously reported in hydronephrotic human kidneys. The cortical interstitial volume fraction in this rabbit model at 16 days is 43.3 +/- 6.1% (+/- 1 SD) in UUO kidneys, 4.9 +/- 3.1% in contralateral kidneys (CLK), and 2.8 +/- 0.8% in kidneys from sham-operated animals (ANOVA, P < 0.0001). Immunohistochemically, UUO is associated with increased interstitial collagens I and III, fibronectin, heparan sulfate proteoglycan and tubulointerstitial nephritis antigen. Aberrant collagen expression is also evident as interstitial collagen IV becomes prominent. Focal, peritubular accumulation of collagens I and II also appear to encircle the TBM. These changes are accompanied by an early, transient increase in renal cortical mRNA encoding the alpha 1 monomers of collagens I, III and IV, implicating increased matrix synthesis in the pathogenesis of obstructive nephropathy. In situ hybridization localized increased expression of alpha 1 (I) and alpha 1 (IV) mRNA to cells in the interstitial space, with clusters of alpha 1(I) positive cells associated with dilated tubules, muscular arteries and the periglomerular interstitium.

In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.

Multi-modal magnetic resonance imaging (MRI) that included high resolution structural imaging, diffusion tensor imaging (DTI), magnetization transfer ratio (MTR) imaging, and magnetic resonance spectroscopic imaging (MRSI) were performed in mild traumatic brain injury (mTBI) patients with negative computed tomographic scans and in an orthopedic-injured (OI) group without concomitant injury to the brain. The OI group served as a comparison group for mTBI. MRI scans were performed both in the acute phase of injury (~24 h) and at follow-up (~90 days). DTI data was analyzed using tract based spatial statistics (TBSS). Global and regional atrophies were calculated using tensor-based morphometry (TBM). MTR values were calculated using the standard method. MRSI was analyzed using LC Model. At the initial scan, the mean diffusivity (MD) was significantly higher in the mTBI cohort relative to the comparison group in several white matter (WM) regions that included internal capsule, external capsule, superior corona radiata, anterior corona radiata, posterior corona radiata, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major and forceps minor of the corpus callosum, superior longitudinal fasciculus, and corticospinal tract in the right hemisphere. TBSS analysis failed to detect significant differences in any DTI measures between the initial and follow-up scans either in the mTBI or OI group. No significant differences were found in MRSI, MTR or morphometry between the mTBI and OI cohorts either at the initial or follow-up scans with or without family wise error (FWE) correction. Our study suggests that a number of WM tracts are affected in mTBI in the acute phase of injury and that these changes disappear by 90 days. This study also suggests that none of the MRI-modalities used in this study, with the exception of DTI, is sensitive in detecting changes in the acute phase of mTBI.