Purpose: Current methods of classification of astrocytoma based on histopathologic methods are often subjective and less accurate. Although patients with glioblastoma have grave prognosis, significant variability in patient outcome is observed. Therefore, the aim of this study was to identify glioblastoma diagnostic and prognostic markers through microarray analysis. Experimental Design: We carried out transcriptome analysis of 25 diffusely infiltrating astrocytoma samples [WHO grade IIödiffuse astrocytoma, grade IIIöanaplastic astrocytoma, and grade IVöglioblastoma (GBM)] using cDNA microarrays containing 18,981 genes. Several of the markers identified were also validated by real-time reverse transcription quantitative PCR and immunohistochemical analysis on an independent set of tumor samples (n = 100). Survival analysis was carried out for two markers on another independent set of retrospective cases (n = 51). Results: We identified several differentially regulated grade-specific genes. Independent validation by real-time reverse transcription quantitative PCR analysis found growth arrest and DNA-damage^inducible a (GADD45a) and follistatin-like 1 (FSTL1) to be up-regulated in most GBMs (both primary and secondary), whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 were up-regulated in the majority of primary GBM. Further, identification of the grade-specific expression of GADD45a and FSTL1 by immunohistochemical staining reinforced our findings. Analysis of retrospective GBM cases with known survival data revealed that cytoplasmic overexpression of GADD45a conferred better survival while the coexpression of FSTL1with p53 was associated with poor survival. Conclusions: Our study reveals that GADD45a and FSTLI are GBM-specific whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1are primary GBM-specific diagnostic markers. Whereas GADD45a overexpression confers a favorable prognosis, FSTL1 overexpression is a hallmark of poor prognosis in GBM patients.

Malignant astrocytomas comprise anaplastic astrocytoma (AA; grade III) and Glioblastoma (GBM; grade IV). GBM is the most malignant with a median survival of 10-12 months in patients. Using cDNA microarray based expression profiling of different grades of astrocytomas, we identified several fold increased levels of PBEF1 transcripts in GBM samples. Pre-B-cell colony enhancing factor 1 gene (PBEF1) encodes Nicotinamide phosphoribosyltransferase (NAmPRTase), which catalyses the rate limiting step in the salvage pathway of NAD metabolism in mammalian cells. Further validation using real time RT-qPCR on an independent set of tumor samples (n = 91) and normal brain samples (n = 9), GBM specific higher expression of PBEF1 was confirmed. Immunohistochemical staining for PBEF1 on a subset of the above samples largely reinforced our finding. We carried out ELISA analysis on serum samples of astrocytoma patients to determine whether this protein levels would correlate with the presence of tumor and tumor grade. PBEF1 serum levels were substantially elevated in many of the AA and GBM patients. Statistical analysis of these data indicates that in patients with astrocytoma, serum PBEF1 levels correlate with tumor grade and is highest in GBM. Immunohistochemical analysis of an independent set of 51 retrospective GBM cases with known survival data revealed that PBEF1 expression in the tumor tissue along with its co-expression with p53 was associated with poor survival. Thus, we have identified PBEF1 as a potential malignant astrocytoma serum marker and prognostic indicator among GBMs.

Object Extraforaminal compression of the L-5 nerve encompasses multiple pathological entities and may result from disc herniations as well as bony (osteophytes or sacral ala) or ligamentous (sacroiliac ligament and lumbosacral band) compression. Several other factors, such as disc space collapse or coronal wedging, can also contribute to narrowing of the extraforaminal space. The extraforaminal space at L5–S1 has unique anatomical features compared with the upper lumbar levels, which makes surgical access to this region difficult. Minimally invasive techniques offer easier access to the region. The purpose of this study was to analyze the contributing factors for extraforaminal compression of the L-5 nerve and assess clinical outcome following surgical decompression. Methods Fifty-two consecutive patients who underwent a minimally invasive far-lateral approach for extraforaminal compression of the L-5 nerve were retrospectively analyzed for clinical data, outcomes, and imaging features (type of disc prolapse, coronal wedging, degree of disc and facet degeneration, facet tropism, foraminal stenosis, osteophytes, and adjacent-level disease). The authors describe the surgical technique used in this study. Results The mean age of the patient sample was 57 years. Sixteen patients each had an extraforaminal ruptured disc or contained protrusion, and the remaining 20 patients had disc protrusions extending into the foraminal region or the lateral recess. Associated foraminal stenosis was found in 38.5%, and adjacent-level stenosis was noted in 22 cases (42.3%) and spondylolisthesis in 4 (7.7%). Osteophytes were noted in 18 cases. A coronal wedging angle ≥ 3° was found in 46.2%, and the laterality of wedging corresponded to the symptomatic side in 91% of cases. Fifteen patients (28.8%) complained of postoperative dysesthesias, which completely resolved in all cases within 6 months. The incidence of dysesthesias was more common in the ruptured disc group. There were no differences in clinical outcome among the different types of disc prolapses. The mean preoperative and postoperative visual analog scale scores were 7.6 and 3.6, respectively. The mean preoperative and postoperative Japanese Orthopaedic Association (JOA) scores were 6.4 and 13.8, respectively. The mean JOA recovery rate was 86.1%. According to the Macnab functional grading system, 96% of the patients had excellent or good grades at follow-up. Conclusions A minimally invasive far-lateral approach to L5–S1 requires a good understanding of the regional anatomy and can provide good to excellent clinical results in properly selected cases. This approach is effective in decompressing the far-lateral and foraminal zones. Adequate preoperative diagnosis and tailoring the surgical procedure to address the relevant compressive element in each case is essential to achieving good clinical results.

✓Osteochondromas are the most common benign bone tumor. Although the metaphysial region of long bones is the usual site of these tumors, the vertebrae may be infrequently affected. The presentation may vary from typical compressive myelopathy to radiculopathy or radiculomyelopathy, depending on the site of involvement. The authors present 3 consecutive cases of cervical spine osteochondromas encountered over 3 years at their institution, each different in its site of involvement, presentation, and chosen treatment. The patient in Case 1 had the typical presentation and lesion site, and was treated with a conventional laminectomy. The patient in Case 2 presented with an extensive disease that required complex, staged surgery with spinal fusion and instrumentation. The patient in Case 3 presented with monoradiculopathy and had a facet joint osteochondroma that was successfully treated with a simple partial facetectomy, without laminectomy.

Object Hydrocephalus is the most common complication of tubercular meningitis (TBM). Relieving hydrocephalus by ventriculoperitoneal (VP) shunt placement has been considered beneficial in patients in Palur Grade II or III. The role of VP shunt placement in those of Grade IV is controversial and the general tendency is to avoid its use. Some authors have suggested that patients in Grade IV should receive a shunt only if their condition improves with a trial placement of an external ventricular drain (EVD). In the present study, the authors assessed the outcome of VP shunt placement in patients in Grade IV TBM with hydrocephalus to examine the factors predicting outcome and to determine whether a trial with an EVD is absolutely necessary prior to shunt placement. Methods Ninety-five consecutive cases of TBM with hydrocephalus in which the patients underwent VP shunt placement were retrospectively analyzed, and direct VP shunts were placed whenever possible. An EVD was placed first only in the presence of deranged blood parameters. Outcomes were assessed both in the short and long term. Results The mean patient age was 17.5 years (range 1–55 years). Fifty-two patients underwent direct VP shunt placement, and the remaining 43 received EVDs first. Overall, 33 and 45% of patients had favorable short- and long-term outcomes, respectively. Age older than 3 years and duration of altered sensorium ≤ 3 days were predictive of a favorable short-term outcome. Glasgow Coma Scale score at presentation was predictive of long-term outcome. Of the patients who did not improve with placement of an EVD prior to VP shunt insertion, 24 and 18% had favorable short- and long-term outcomes, respectively; this was not significantly different from the outcome in the patients who underwent direct VP shunt placement. Conclusions Direct VP shunt placement is an effective option in patients with Grade IV TBM with hydrocephalus. Age and duration of altered sensorium are predictive of short-term outcome, while Glasgow Coma Scale score at presentation predicts long-term outcome. Ventriculoperitoneal shunts should be considered even in patients who do not improve with an EVD.

Introduction: Focal intradural infections of the brain include empyema and abscess in the supratentorial and infratentorial spaces. These are amenable to surgical management. Various other issues may complicate the course of management, e.g. hydrocephalus with infratentorial lesions or cortical venous thrombosis with supratentorial lesions. Here, we review the management and identify factors affecting outcome in these patients. Materials and Methods: This is a retrospective analysis of all children (aged <18 years) treated at the National Institute of Mental Health and Neurosciences, Bangalore, India, between 1988 and 2004. Case records were analyzed to obtain clinical, radiological, bacteriological and follow-up data. Results: There were 231 children who underwent treatment for focal intradural abscess/empyema at our institute. These included 57 children with cerebral abscess, 65 with supratentorial empyema, 82 with cerebellar abscess and 27 with infratentorial empyema. All patients underwent emergency surgery (which was either burr hole and aspiration of the lesion or craniotomy/craniectomy and excision/evacuation), along with antibiotic therapy, typically 2 weeks of intravenous and 4 weeks of oral therapy. The antibiotic regimen was empiric to begin with and was altered if any sensitivity pattern of the causative organism(s) could be established by culture. Hydrocephalus was managed with external ventricular drainage initially and with ventriculoperitoneal shunt if warranted. Mortality rates were 4.8% for cerebral abscess, 9.6% for cerebellar abscess, 10.8% for supratentorial subdural empyema and 3.7% for posterior fossa subdural empyema. The choice of surgery was found to have a strong bearing on the recurrence rates and outcome in most groups, with aggressive surgery with craniotomy leading to excellent outcomes with a low incidence of residual/recurrent lesions. Conclusions: Antibiotic therapy, emergency surgery and management of associated complications are the mainstays of treatment of these lesions. We strongly advocate early, aggressive surgery with antibiotic therapy in children with focal intradural infections.

Background: Supraorbital craniotomy (SOC) has brought a paradigm shift in approaching anterior skull base lesions. With better understanding of relevant anatomy, the indications are being stretched from highly selected, small-to-moderate-sized tumors to large and complex anterior skull base lesions. Objective: We share our experience and discuss the nuances of surgery for large anterior skull base meningiomas using the SOC. Methods: This is a single institute study using prospectively collected retrospective data from seven cases of large anterior skull base meningiomas (>3 cm) using the SOC. We reviewed the indications, safety, and procedural complications in these cases. Results: Simpson's Grade 2 excision was achieved in all these seven cases, with faster postoperative recovery. Follow-up clinical outcome and cosmesis were satisfactory. Conclusion: SOC is a safe alternative for the standard skull base approaches in treating large anterior skull base meningiomas. The SOC can be effectively used to treat selected large anterior skull base meningiomas.

We propose a clinical-histological-immunohistochemical' model for medulloblastoma where extent of resection, administration of chemotherapy, presence of gross anaplasia and c-erb B2 overexpression status are the most important predictors of recurrence rates.