Craniotomy with Ridges: A Time and Cost-Efficient Technique for Unwavering Fixation of Bone Flap.

After advent of the power driven tools, the ease of surgeons and pace of surgery has been enhanced. Nowadays, most of the neurosurgeons are tend to use the motorized drills for elevating a bone flap to make a craniotomy. The bone cutting by the craniotome is wide and nonbeveled, which mandates the fixation of bone flap at closure, either by wiring, miniplates, or other fixation techniques. This not only lengthens the duration of surgery but also adds extra cost of miniplates to the patient. Here we are presenting a novel technique of elevating a bone flap where fixation at the end of surgery is not obligatory, without any risk of sinking of bone flap into the craniotomy defect.

Endoscopic Management of Intraventricular Neurocysticercosis.

AIM: To evaluate the technique and outcome of endoscopic management of intraventricular neurocysticercosis (NCC). MATERIAL AND METHODS: We retrospectively analysed the records of 30 consecutive patients of intraventricular (intra-third and fourth ventricle) NCC who underwent endoscopic management. The clinical profiles of the patients were evaluated which included age, symptoms and signs. Transcranial endoscopy was performed through a frontal burr hole using a Gaab Universal Endoscope system with rigid 0° and 30° telescope for endoscopic third ventriculostomy and removal of the cyst was described. The mean follow-up period was 22.6 months. RESULTS: In 86.67% (26/30) patients we are able to visualize/excise/decompress the cyst. We were able to successfully excise all the third ventricular cysts (16/16) and in 66.67% (8/12) of the fourth ventricular cysts. In 90% (27/30) patients we were able to successfully divert the CSF flow and achieve long-term shunt free period. CONCLUSION: We found that endoscopic cerebrospinal fluid (CSF) diversion in cases of intraventricular NCC is feasible and associated with high success rate. Endoscopic CSF diversion in NCC related hydrocephalus usually produces a long-term cure.

Central nervous system mycosis: analysis of 10 cases.

AIM: To describe the clinicopathological features in patients with fungal infections of the central nervous system (CNS) presenting as mass lesions. MATERIALS AND METHODS: A retrospective analysis of records obtained from 10 patients was done with histopathologically confirmed fungal infections presenting as ICSOL, diagnosed in the department of pathology. Clinical features at presentation, findings of radiological investigations performed and histopathology were noted for each patient and subjected for analysis. RESULTS: Infection was higher in males, and paranasal sinusitis was the most common predisposing factor. Location was intraparenchymal followed by sphenoid wing. Four dural-based lesions mimicked meningioma clinically. The most common fungus identified was zygomycosis (seven cases), followed by phaeohyphomycosis (two cases) and aspergillosis (one case). CONCLUSION: There is a rising trend of CNS mycosis, both in immunocompromised and immunocompetent patients. Intracranial fungal granuloma may mimic radiologically as glioma or meningioma, therefore a high index of suspicion is needed to detect early CNS fungal infections, especially in immunocompetent young patients with no predisposing illness. Fungi should always be excluded in patients with inflammatory or granulomatous pathology of CNS.

Subcompartmentalization of extracellular extravascular space (EES) into permeability and leaky space with local arterial input function (AIF) results in improved discrimination between high- and low-grade glioma using dynamic contrast-enhanced (DCE) MRI.

PURPOSE: To modify the generalized tracer kinetic model (GTKM) by introducing an additional tissue uptake leakage compartment in extracellular extravascular space (LTKM). In addition, an implicit determination of voxel-wise local arterial input function (AIF) Cp (t) was performed to see whether these changes help in better discrimination between low- and high-grade glioma using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). MATERIALS AND METHODS: The modified model (LTKM) was explored and fitted to the concentration-time curve C(t) of each voxel, in which the local AIF Cp (t) could be estimated by a time invariant convolution approximation based on a separately measured global AIF Ca (t). A comparative study of tracer kinetic analysis was performed on 184 glioma patients using DCE-MRI data on 1.5T and 3T MRI systems. RESULTS: The LTKM analysis provided more accurate pharmacokinetic parameters as evidenced by their relative constancy with respect to the length of concentration-time curve used. In addition, LTKM with local AIF resulted in improved discrimination between low-grade and high-grade gliomas. CONCLUSION: LTKM with local AIF provides more accurate estimation of physiological parameters and improves discrimination between low-grade and high-grade gliomas as compared with GTKM.

Unilateral hydrocephalus: atypical presentation of intracranial tuberculoma.

A 43-year-old male presented with 3-month history of low-grade fever and headache. Radiological investigations revealed unilateral hydrocephalus. Unilateral obstruction of the foramen of Monro due to chronic tubercular ependymal inflammation was suspected and endoscopic septostomy was planned. Though ventriculo-peritoneal shunt is a simple method to treat hydrocephalus, complications related to this procedure are numerous. Neuroendoscopy is a safe method to treat hydrocephalus in selected cases, and also provides access to biopsy the lesion in question. An isolated tuberculoma obstructing the foramen of Monro was seen during endoscopy. Presentation and management of this unusual tuberculoma is reported along with a review of the pertinent literature.

The transparaspinal approach: A novel technique for one-step removal of dumb-bell-shaped spinal tumors.

Complex dumb-bell spinal tumors are challenging surgical lesions. Combined antero-posterior exposures have traditionally been used in their management. This combined exposure has the disadvantage of a two-stage operation with transthoracic or retroperitoneal dissection. With better understanding of biomechanics of spine and evolution of microsurgical technique, there has been resurgence of single stage surgeries, among which the transparaspinal exposure provides the simplest and the most direct route for resection of dumb-bell tumors. A 16-year-old male was admitted with history of back pain with radiation to left lower limb for 6 months, progressive weakness of both lower limbs for two months, and hesitancy of micturition for 1 month. A clinical diagnosis of cauda-conus lesion was made. Radiological investigations revealed a complex dumb-bell spinal tumor extending from lower part of L2-L4 vertebra, with large paraspinal extension through left L3 intervertebral foramina. Tumor was successfully removed in one step using a transparaspinal approach. We discuss technical details of this novel approach along with limitations and possible complications.

Intraoperative ventriculo-stomographic evaluation of endoscopic cerebrospinal fluid diversion and flow restoration procedures.

PURPOSE: This prospective study was designed for intra-operative demonstration of cerebrospinal fluid (CSF) flow in ventricles and cisternal spaces before and after neuroendoscopic procedure. The aim of this study was to evaluate site of obstruction of CSF flow and subsequent stomal or aqueductal patency after endoscopic third ventriculostomy (ETV) or aqueductoplasty in patients with hydrocephalus of diverse aetiology. METHOD: Seventeen patients with hydrocephalus due to diverse aetiology underwent ETV (n = 15) and aqueductoplasty (n = 2) or cysto-ventrticulostomy (n = 1) or transaqueductal removal of neurocysticercus cyst (NCC) (n = 1). Intra-operatively, radio-opaque contrast agent (iohexol) instillation into the third ventricle was used for qualitative evaluation of obstruction and post-procedure CSF flow across the stoma into cisternal spaces. RESULT: 11 male and 6 female patients ranging from 3 to 50 years of age were included in the study. Post-procedure intra-operative ventriculo-stomography (IOVSG) showed free flow of dye across the endoscopic stoma (n = 13) or aqueduct (n = 2) into cisternal spaces. Diagnosis of fourth ventricular NCC was made in one patient with panventriculomegaly. In two patients of tuberculous meningitis hydrocephalus, poor flow of contrast in the prepontine area and basal cisterns was seen on IOVSG. They were subjected to ventriculoperitoneal shunt insertion in the same sitting. Cine MRI confirmed the patency of stoma or aqueduct in follow-up period in all patients with successful endoscopic procedure. CONCLUSION: IOVSG is a simple and safe technique that helps in confirming the adequacy of endoscopic procedure during surgery and thereby facilitates intra-operative decision about further management.

Proliferating cell nuclear antigen, p53 and micro vessel density: Grade II vs. Grade III astrocytoma.

Histological classification and grading are prime procedures in the management of patients with astrocytoma, providing vital data for therapeutic decision making and prognostication. However, it has limitations in assessing biological tumor behavior. This can be overcome by using newer immunohistochemical techniques. This study was carried out to compare proliferative indices using proliferating cell nuclear antigen (PCNA), extent of p53 expression and micro vessel morphometric parameters in patients with low grade and anaplastic astrocytoma. Twenty-five patients, each of grade II and grade III astrocytoma were evaluated using monoclonal antibodies to PCNA, p53 protein and factor VIII related antigen. PCNA, p53-labeling indices were calculated along with micro vessel morphometric analysis using Biovis Image plus Software. Patients with grade III astrocytoma had higher PCNA and p53 labeling indices as compared with grade II astrocytoma (29.14 plus/minus 9.87% vs. 16.84 plus/minus 6.57%, p 0.001; 18.18 plus/minus 6.14% vs. 6.14 plus/minus 7.23%, p 0.001, respectively). Micro vessel percentage area of patients with grade III astrocytoma was also (4.26 plus/minus 3.70 vs. 1.05 plus/minus 0.56, p 0.001), higher along with other micro vessel morphometric parameters. Discordance between histology and one or more IHC parameters was seen in 5/25 (20%) of patients with grade III astrocytoma and 9/25 (36%) of patients with grade II disease. PCNA and p53 labeling indices were positively correlated with Pearson's correlation, p less than 0.001 for both). Increased proliferative fraction, genetic alterations and neovascularization mark biological aggressiveness in astrocytoma. Immunohistochemical evaluation scores over meet the challenge of accurate prognostication of this potentially fatal malignancy.

Tumor irrigation fluid enhances diagnostic efficacy in endoscopic biopsies of intracranial space-occupying lesions.

PURPOSE: Intraventricular neuroendoscopic CNS biopsiesare small, fragmented, and tissue is frequently inadequate for diagnosis. We have attempted to increase cellular yield using tumor irrigation fluid (TIF) and a cyto-histological approach for diagnosis of intracranial tumors, cysts, and infections. METHODS: A retrospective group of 147 cases, where only endoscopic biopsies were obtained, was compared with a prospective group of 31 cases where along with the endoscopic biopsies, tumor irrigation fluid (TIF) was collected. Tumor cyst fluid was obtained from cystic tumors (n=6). Small tumor fragments in the TIF were utilized to make squash smears (n=31). Clotted fragments were processed for sections in (n=3). Centrifuged deposit smears were prepared from tumor irrigation fluid and tumor cyst fluid. RESULTS: Conclusive pathological diagnosis in endoscopic biopsies could be arrived at in 77.4% (24/31) prospective cases and 80.3% (118/147) in retrospective cases. Collection of TIF with a cyto-histological diagnostic approach gave a significantly higher rate of conclusive pathological diagnosis in 93.5% (29/31) cases in the prospective group. CONCLUSIONS: Additional tissue from TIF preserves the original biopsy, provides more material for diagnosis and gives a better morphological picture in smears. Hence diagnosis of endoscopic CNS biopsies can be rendered in more cases and with greater degree of confidence.

Surgical outcome of tuberculous meningitis hydrocephalus treated by endoscopic third ventriculostomy: prognostic factors and postoperative neuroimaging for functional assessment of ventriculostomy.

OBJECT: 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.

Combined trans-sphenoidal and simultaneous trans-ventricular-endoscopic decompression of a giant pituitary adenoma: case report.

OBJECTIVE: This is the first report of the simultaneous combined use of trans-sphenoidal and trans-ventricular-endoscopic route for decompression of a giant pituitary adenoma. METHOD: A 38 year old man presented to us with symptoms of raised intracranial pressure along with visual and hypothalamic disturbances. The CT scan revealed destruction of the sella by a large (5 x 3.5 x 2.5 cm) well defined enhancing mass in the sella and suprasellar region extending laterally up to the cavernous sinuses and both carotid arteries and superiorly into the lumen of the 3rd ventricle producing obstructive hydrocephalus. On T2WI of the non-contrast MRI scan the mass was iso-intense to grey matter suggesting the possibility of a firm nature of the adenoma. The tumour was first approached by the standard trans-sphenoidal route and as predicted from the pre-operative MRI, the tumour was found to be firm and not amenable to suction. After decompression of the intra-sellar part of the tumour, the intracranial pressure was raised in an attempt to make the remainder of the tumour descend into the sella but without success. The suprasellar part of the tumour was then simultaneously addressed via a trans-ventricular-endoscopic route but the firm tumour did not yield to endoscopic instruments viz. biopsy forceps, angiographic catheter and electrosurgical probes. It was then gently pushed down towards the sella and decompressed piecemeal by using trans-sphenoidal instruments. The sellar cavity was reconstructed using fat, fascia lata graft and a piece of septal bone. RESULTS: Post-operatively, the patient showed a remarkable improvement of his symptoms of raised intracranial pressure, hypothalamic dysfunction and visual disturbances. Follow-up imaging at 2 months and 1 year, did not show any residual or recurrent tumour. CONCLUSIONS: This novel technique of the combined trans-sphenoidal and simultaneous trans-ventricular-endoscopic approach is a viable option for patients with giant fibrous pituitary adenoma when the tumour is not yielding to the trans-sphenoidal route alone.

Endoscopic diagnosis of a pineal papillary glioneuronal tumor with extensive ventricular involvement: case report with review of literature.

Papillary glioneuronal tumor (PGNT) is a newly described mixed glioneuronal tumor, recently included in the World Health Organization classification of central nervous system tumors. We report morphologic and immunohistochemical characteristics PGNT of the pineal region extending into the third and lateral ventricles in a four-year-old male child and reviewed all the cases reported in the international literature till date. In this child the diagnosis of PGNT was established by endoscopic biopsy and squash smear examination.

Role of diffusion tensor imaging metrics and in vivo proton magnetic resonance spectroscopy in the differential diagnosis of cystic intracranial mass lesions.

The purpose of this study was to determine whether proton magnetic resonance spectroscopy (PMRS) and diffusion tensor imaging (DTI) indices, fractional anisotropy (FA) and mean diffusivity (MD) can be used to distinguish brain abscess from cystic brain tumors, which are difficult to distinguish by conventional magnetic resonance imaging (MRI). Fifty-three patients with intracranial cystic mass lesions and 10 normal controls were studied. Conventional MRI, PMRS and DTI of all the patients were performed on a 1.5-T GE scanner. Forty patients were with brain abscess and 13 with cystic tumors. Cytosolic amino acids (AAs) were present in 32 of 40 brain abscess patients. Out of 13 patients with cystic tumors, lactate and choline were seen in 3 and only lactate was present in 10 patients on PMRS. All 40 cases of abscess had high FA, while all 13 cases of tumor cysts had high MD values. We conclude that FA measurements are more sensitive in predicting the abscess, while PMRS and MD are more specific in differentiating abscess from cystic tumors. We suggest that PMRS should be combined with DTI rather than with diffusion-weighted imaging as FA can be used as an additional parameter for separation of abscess from other cystic intracranial mass lesions.

Dynamic contrast-enhanced (DCE) derived transfer coefficient (ktrans) is a surrogate marker of matrix metalloproteinase 9 (MMP-9) expression in brain tuberculomas.

PURPOSE: To correlate dynamic contrast-enhanced (DCE) MRI derived perfusion indices with immunohistochemically obtained vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in a cellular fraction of brain tuberculomas (BT). MATERIALS AND METHODS: Thirteen BT patients underwent DCE MRI. Perfusion indices (cerebral blood volume [CBV], transfer coefficient [ktrans] and leakage [ve]) maps were generated for the quantitative analysis. The CBV was corrected for the leaky blood-brain barrier (BBB). The relative CBV (rCBV), ktrans, and ve were calculated by placing 10 regions of interest (ROIs) showing the highest values in the lesion. The percentage area of VEGF and percentage area of MMP-9 and microvessel density (MVD) were quantified from 10 fields per lesion with maximal expression of the excised BT. Pearson correlation analysis between physiological indices and quantitative VEGF, MMP-9, and MVD was performed for each ROI. RESULTS: The average value of rCBV, ktrans, ve, VEGF, MMP-9, and MVD were 3.53+/-0.37, 2.04+/-0.40 min(-1), 0.71+/-0.09, 12.51+/-2.56, 18.09+/-2.06, 10.87+/-1.99, respectively. The ktrans (r=0.918, P<0.001) and ve (r=0.899, P<0.001) showed significant correlation with MMP-9, while rCBV correlated significantly with MVD (r=0.962, P<0.001) and VEGF (r=0.868, P<0.001). CONCLUSION: We conclude that the expression of MMP-9, a marker of BBB disruption and disease activity in BT correlates with DCE-derived ktrans and thus has the potential to be used as its surrogate marker.

Utility of cysticercus fasciolaris antigen in Dot ELISA for the diagnosis of neurocysticercosis.

BACKGROUND: Clinical diagnosis of neurocysticercosis (NC) is established by CT scan and MRI. However, absolute diagnosis is not possible in a fair number of cases, and serological assays are used as adjunct. Besides, CT scan and MR imaging are resource-intensive tests and not practical for screening in endemic areas. AIM: To provide a low-cost, efficient, and reproducible assay for the detection of antibodies against cysticerci. Hence we have attempted to standardize and evaluate the diagnostic utility of the cysticercus fasciolaris antigen in a Dot ELISA assay for diagnosis of NC. SETTING AND DESIGN: Tertiary hospital-based, case-control series. MATERIALS AND METHODS: Confirmed cases of NC diagnosed by presence of ring lesions in CT scan or MR imaging with presence of scolex were taken as positive controls (n = 50). Negative controls (n = 50) included subjects with normal CT scan studies (n = 30) and diseased controls with ring lesions in CT scan confirmed to be neurotuberculosis (n = 20). Dot ELISA was standardized and validated with commercially available ELISA (UBI, USA) using sera from the study groups. STATISTICAL ANALYSIS: Chi-square test was used to compare the immunodiagnostic performance of the two tests. P value less than .05 (P < 0.05) was considered significant. RESULTS: The Dot ELISA had a sensitivity of 88% and specificity of 74% with a positive predictive value of 77.19% and negative predictive value of 81.06%. Likelihood ratios for a positive and a negative test were 3.4 and 0.2. The sensitivity and specificity of commercial ELISA were 92% and 84% respectively. Difference between the performances of the two tests was not significant statistically. CONCLUSIONS: Dot ELISA has sensitivity and specificity comparable to ELISA for the diagnosis of NC. The test is simpler, not requiring expertise and instrumentation. Further validation of the test as a screening tool is required.

Role of endoscopic third ventriculostomy in patients with communicating hydrocephalus: an evaluation by MR ventriculography.

Post-tubercular meningitic hydrocephalus (TBMH) and post-traumatic hydrocephalus (PTH) is often considered a contraindication for endoscopic third ventriculostomy (ETV), as it is mostly of communicating type in these cases. The aim of the present study was to define the role of ETV in patients with communicating hydrocephalus. Ten consecutive patients of TBMH, PTH and postneurocysticercus (NCC) hydrocephalus were formed the study group. Diagnosis of communicating hydrocephalus was made using magnetic resonance ventriculography (MRV). If contrast was seen coming out from the ventricular system into the basal cisterns, it was considered as communicating hydrocephalus. Patients with clinical and imaging evidence of raised intracranial pressure and failed medical treatment were taken up for ETV. All patients were studied by preoperative and postoperative MRV. Success of the procedure was assessed by the improvement in clinical and imaging parameters on postprocedure follow-up in all these cases. Technically successful ETV was performed in all 10 patients. Overall success rate of ETV in communicating hydrocephalus was 70% (n = 7). The shunt surgery was performed in the remaining three patients with ETV failure. One patient developed complication following postoperative MRV and was managed conservatively. We conclude that ETV is effective in post-TBM, post-traumatic communicating and post-NCC communicating hydrocephalus and should be considered as initial surgical option for cerebrospinal fluid diversion in these patients. MRV is a relatively safe technique to ascertain the patency of subarachnoid space as well as ETV stoma.

Differentiation of infective from neoplastic brain lesions by dynamic contrast-enhanced MRI.

INTRODUCTION: It is not always possible to differentiate infective from neoplastic brain lesions with conventional MR imaging. In this study, we assessed the utility of various perfusion indices in the differentiation of infective from neoplastic brain lesions. METHODS: A total of 103 patients with infective brain lesions (group I, n=26) and neoplastic brain lesions (high-grade glioma, HGG, group II, n=52; low-grade glioma, LGG, group III, n=25) underwent dynamic contrast-enhanced MR imaging. The perfusion indices, including relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), transfer coefficient (k(trans)) and leakage (v(e)), were calculated and their degree of correlation with immunohistologically obtained microvessel density (MVD) and vascular endothelial growth factor (VEGF) determined. The rCBV was corrected for the leakage effect. Discriminant analysis for rCBV, rCBF, k(trans) and v(e) was performed to predict the group membership of each case and post hoc analysis was performed to look for group differences. RESULTS: The rCBV, rCBF, k(trans), v(e), MVD and VEGF were significantly different (P<0.001) between the three groups. Discriminant analysis showed that rCBV predicted 73.1% of the infective lesions, 84.6% of the HGG and 72.0% of the LGG. The rCBF classified 86.5% of the HGG, 80.0% of the LGG and 65.4% of the infective lesions. The k(trans) discriminated 98.1% of the HGG, 76.0% of the LGG and 88.5% of the infective lesions correctly. The v(e) classified 98.1% of the HGG, 76.0% of the LGG and 84.6% the infective lesions. The rCBV was correlated significantly with MVD and VEGF, while the correlation between k(trans) and MVD was not significant. CONCLUSION: Physiological perfusion indices such as k(trans) and v(e) appear to be useful in differentiating infective from neoplastic brain lesions. Adding these indices to the current imaging protocol is likely to improve tissue characterization of these focal brain mass lesions.

Lymphocyte transformation test: a new method for diagnosis of neurocysticercosis.

Neurocysticercosis (NCC) is the commonest parasitic disease of the central nervous system. Neuroimaging tools are considered gold standard for the diagnosis of NCC, but its availability is restricted in developing countries. So, there is a definite need for reliable immunodiagnostic tool. The aim of the present study was to evaluate cyst fluid antigen-based lymphocyte transformation test (LTT) as a diagnostic tool for NCC. Tissue culture plates (96 wells) were coated with cyst fluid having protein concentration of 20 mug/well. Freshly isolated lymphocytes from 48 symptomatic NCC cases, 39 matched disease controls, and 40 healthy volunteers were seeded at a concentration of 1 x 10(6) cells/well. LTT was performed as per standard guidelines and (3)H-thymidine was used to measure cell proliferation. The cutoff stimulation index (SI) was defined as mean of controls +2 SD. The mean SI of the cell proliferation for NCC cases was significantly higher than controls (5.83 versus 1.29, P < 0.001). The sensitivity and specificity of LTT for diagnosis of NCC were 93.8% and 96.2%, respectively. The study shows that LTT can be used as an immunodiagnostic tool for NCC; however, it needs to be validated in other endemic areas.

Vascular endothelial growth factor as a marker of disease activity in neurotuberculosis.

Vascular endothelial growth factor (VEGF) is a potent angiogenesis mediator. Scant reports are available defining the role of VEGF in active and inactive tubercular meningitis (TBM) with no studies on brain tuberculoma. We quantified VEGF levels by enzyme linked immunoassay (ELISA) in cerebrospinal fluid (CSF) and serum in 20 cases each with active and inactive TBM as well as 22 cases of intraparenchymal tuberculoma. VEGF expression and microvessel angiogenesis quantification was done in 7 cases where tuberculomas were excised. Significantly increased VEGF levels in CSF were found in active TBM cases (106.0+/-50.0 pg/ml) compared to inactive TBM cases (14.7+/-10.0 pg/ml) (p<0.001). Mean serum VEGF levels in active TBM, inactive TBM and tuberculoma were 694.93+/-820.66 pg/ml, 499.61+/-238.33 pg/ml and 541.0+/-389.0 pg/ml, respectively. Immunohistochemical staining of excised tuberculoma demonstrated high expression of VEGF in granulomatous areas with intense positivity in inflammatory mononuclear cells, Langhan's giant cells as well as reactive astrocytes and fibrocytes. A strong positive correlation was observed between microvessel density and VEGF expression. Serial decrease in serum VEGF levels was observed with increasing duration of therapy in tuberculoma. We conclude that increased CSF and serum VEGF levels are a measure of activity of the disease in neurotuberculosis and its gradual decrease over a period of time is probably an indicator of therapeutic response.

Comparisons between scolex and membrane antigens of Cysticercus fasciolaris and Cysticercus cellulosae larvae for immunodiagnosis of neurocysticercosis.

The antigen source for enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunotransfer blot for neurocysticercosis is generally Taenia solium. A comparison of the membrane and scolex extracts of Cysticercus cellulosae and Cysticercus fasciolaris (larval stage of Taenia taeniaeformis) for the immunodiagnosis of neurocysticercosis has been performed. C. fasciolaris cysts were produced experimentally in rat liver. C. cellulosae was obtained from muscle of infected pigs. The antigen extracts of membrane and scolex were compared using ELISA in 50 patients and 50 control participants to detect immunoglobulin (Ig) G or IgM antibodies. Proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were immunoprobed using pooled and individual sera. The gold standard for diagnosis was visualization of scolex in ring lesions by magnetic resonance imaging or computed tomography scans. ELISA for IgG antibodies using C. fasciolaris membrane had the highest sensitivity of 94%. Specificity ranged from 78% to 90%. Immunoreactive bands common to all 4 antigens were seen between 60 and 70 kDa and 40 and 45 kDa. The presence of comparative antigenic bands between human and rat pathogens provides convincing evidence for use of C. fasciolaris antigens for immunodiagnostic procedures. The antigen can be produced in small animals in standardized laboratory conditions within 60 days.