Artery of Percheron infarction after endoscopic pituitary surgery.

Infarction in the artery of Percheron territory is a rare phenomenon in which occlusion of an unpaired perforating artery arising from the P1 segment on one side results in infarcts in the bilateral paramedian thalami with or without midbrain infarcts. We describe the case of a 40-year-old male who developed this complication following re-exploratory trans-sphenoidal surgery for a pituitary adenoma. In this first report of its kind in endoscopic pituitary surgery, the pathogenesis and clinico-radiological features of this rare vascular event are discussed.

An interesting case of post traumatic tibialis anterior muscle herniation.

A muscle hernia is defined as a protrusion of the muscle belly through an acquired or congenital fascial defect. Muscle herniation through fascia is a relatively rare entity. Though predominantly asymptomatic, rarely they can be cause of vague pain in the leg, aggravated by exercises. Various conservative measures have been described for asymptomatic hernias, but treatment of symptomatic cases remains controversial. Here we present a case of symptomatic post traumatic tibialis anterior muscle herniation which was treated successfully with autologous fascia lata graft in Yenepoya Medical College, Mangalore in the month of January 2013. Muscle hernias should be kept in mind as a rare differential diagnosis whenever patients present with persisting vague leg pain with or without swelling. If conservative treatment fails, we recommend closure with autologous graft or fasciotomy to relieve the symptoms.

A clinicopathological study of diagnostically challenging meningioma mimics.

The occurrence of neoplastic and nonneoplastic dural based masses that mimic meningiomas is infrequent and may not be considered during radiological and intraoperative analysis. We describe single institute study of 20 such rare cases. This study included total of 20 cases of meningioma mimics. The clinical, radiological and histopathological findings were evaluated. Tissue fixed in 10% formalin was routinely processed and 5 µ thick sections were cut and stained with hematoxylin & eosin. Histochemistry and immunohistochemistry using avidin-biotin complex immunoperoxidase method was done wherever indicated. In the present study group, 15 were male and 5 female with a male: female ratio of 3:1. The age ranged from 14 to 78 years. Radiologically all these lesions were extra-axial in location, predominantly hypointense on T2W, isointense on T1W images and showed intense homogenous enhancement on contrast administration. Four cases were in pediatric age group with histopathological diagnosis of Rosai Dorfman disease, medulloblastoma, hemangiopericytoma and malignant melanoma. In the adult population, the histopathological diagnoses were hemangiopericytoma, undifferentiated sarcoma, extraskeletal osteosarcoma, Rosai Dorfman disease, medulloblastoma, and metastases from systemic malignancies. Of the total 6 cases of metastases 1 was nonseminomatous germ cell tumor from a primary in testis, 1 was adenocarcinoma from an unknown primary, and 4 were adenocarcinoma from lung. There was a single case of dural based frontal lobe malignant melanoma with congenital hairy nevi on anterior chest wall, scalp, anterior abdominal wall and inguinal region. As the management and biologic behaviour of many of the MM are different, it is essential to familiarize ourselves to them.

Higher topoisomerase 2 alpha gene transcript levels predict better prognosis in GBM patients receiving temozolomide chemotherapy: identification of temozolomide as a TOP2A inhibitor.

The search for molecular markers which predict response to chemotherapy is an important aspect of current neuro-oncology research. MGMT promoter methylation is the only proved marker of glioblastoma. The purpose of this study was to assess the effect of topoisomerase expression on glioblastoma survival and study the mechanisms involved. The transcript levels of all isoforms of the topoisomerase family in all grades of diffuse astrocytoma were assessed. A prospective study of patients with glioblastoma treated by a uniform treatment procedure was performed with the objective of correlating outcome with gene expression. The ability of TOP2A enzyme to relax the super coiled plasmid DNA in the presence of temozolomide was evaluated to assess its effect on TOP2A. The temozolomide cyctotoxicity of TOP2A-silenced U251 cells was assessed. The transcript levels of TOP2A, TOP2B, and TOP3A are upregulated significantly in GBM in comparison with lower grades of astrocytoma and normal brain samples. mRNA levels of TOP2A correlated significantly with survival of the patients. Higher TOP2A transcript levels in GBM patients predicted better prognosis (P = 0.043; HR = 0.889). Interestingly, we noted that temozolomide inhibited TOP2A activity in in-vitro enzyme assays. We also noted that siRNA knock down of TOP2A rendered a glioma cell line resistant to temozolomide chemotherapy. We demonstrated for the first time that temozolomide is also a TOP2A inhibitor and established that TOP2A transcript levels determine the chemosensitivity of glioblastoma to temozolomide therapy. Very high levels of TOP2A are a good prognostic indicator in GBM patients receiving temozolomide chemotherapy.

Isolated sellar tuberculoma presenting with panhypopituitarism: clinical, diagnostic considerations and literature review.

Tuberculosis, a common cause for chronic intracranial infections can mimic varied intracranial pathologies including tumours. Pituitary tuberculomas are rare lesions and are often diagnosed pre-operatively as pituitary tumours. We report a case of a 31-year-old lady with a sellar-suprasellar lesion who presented with panhypopituitarism. The patient underwent a trans-nasal, trans-sphenoidal surgical decompression of the lesion. Histopathology revealed a tuberculous lesion in the pituitary. The characteristic radiological features of sellar tuberculomas are discussed along with a review of literature. Atypical sellar radiology in the presence of a thickened pituitary stalk could point to pathology other than pituitary adenoma, possibly a chronic inflammatory condition like tuberculoma.

Angiolipoma in sellar, suprasellar and parasellar region: report on two new cases and review of literature.

Angiolipomas of CNS are very rare; more than 90% involve the spinal canal. There are only a few case reports documenting the tumor in the sellar/suprasellar region. We report 2 cases of angiolipoma involving sellar/suprasellar and right parasellar region in two female patients. On histopathology the lesion was composed of vascular component which was of cavernous type in one patient and of capillary caliber in the other with admixture of mature adipocytes. The MRI findings were distinctive as the lesion was predominantly iso-to-hypointense on T1W sequence, hyperintense on T2WI and FLAIR sequence. In addition, a few small hyperintense areas were noted on plain T1W images which may represent intralesional fat. One of the cases also showed lipid lactate peak on MR spectroscopy. To the best of our knowledge only 8 other cases of sellar, parasellar angiolipomas have been reported in indexed literature. MRI with fat suppression sequences should be routinely performed in lesions in such locations with hyperintense areas on T1WI as the incidence of intraoperative blood loss is very high. A preoperative suspicion of the diagnosis might help in reducing the patient morbidity.

Proteomic identification of haptoglobin α2 as a glioblastoma serum biomarker: implications in cancer cell migration and tumor growth.

Glioblastoma (GBM; grade IV astrocytoma) is the most malignant and common primary brain tumor in adults. Using combination of 2-DE and MALDI-TOF MS, we analyzed 14 GBM and 6 normal control sera and identified haptoglobin α2 chain as an up-regulated serum protein in GBM patients. GBM-specific up-regulation was confirmed by ELISA based quantitation of haptoglobin (Hp) in the serum of 99 GBM patients as against lower grades (49 grade III/AA; 26 grade II/DA) and 26 normal individuals (p = 0.0001). Further validation using RT-qPCR on an independent set (n = 78) of tumor and normal brain (n = 4) samples and immunohistochemcial staining on a subset (n = 42) of above samples showed increasing levels of transcript and protein with tumor grade and were highest in GBM (p = <0.0001 and <0.0001, respectively). Overexpression of Hp either by stable integration of Hp cDNA or exogenous addition of purified Hp to immortalized astrocytes resulted in increased cell migration. RNAi-mediated silencing of Hp in glioma cells decreased cell migration. Further, we demonstrate that both human glioma and mouse melanoma cells overexpressing Hp showed increased tumor growth. Thus, we have identified haptoglobin as a GBM-specific serum marker with a role on glioma tumor growth and migration.

A peri-trigonal giant tumefactive cavernous malformation: case report and review of literature.

INTRODUCTION: Giant cavernous malformations (GCMs) constitute an uncommon entity in the diagnostic armamentarium of the neurosurgeon. We report a 3-year-old boy with a GCM in the peri-trigonal region and review 13 other paediatric cases previously reported in literature. CASE: A 3-year-old boy presented with right-sided hemiparesis and features of raised intracranial pressure of short duration. Computed tomography showed a large left peri-trigonal mass with a bleed. Magnetic resonance imaging showed associated perilesional edema and mass effect, rendering the lesion a tumefactive appearance. He underwent total excision of the lesion, with subsequent recovery of hemiparesis. Histopathology was reported as a cavernoma. DISCUSSION: The clinico-radiological presentation of GCM is discussed based on a case report and relevant cases in literature. Good surgical outcome can be expected with total microsurgical excision. CONCLUSION: A giant cavernous malformation should be one of the differentials of a lesion with a tumefactive clinico-radiological presentation in children. There should be a high index of suspicion for such a diagnosis, especially when the lesion does not enhance with contrast. This is the third case report in paediatric literature describing a periventricular location of this unusual lesion.

Morphometric analysis of foramen magnum dimensions and intracranial volume in pediatric Chiari I malformation.

PURPOSE: Foramen magnum dimensions and intracranial volume in Chiari I malformations in children were studied, and the statistical relationship between patient demographics, radiological features and foramen magnum morphometry was investigated. METHODS: Linear measurements were used to calculate the intracranial volume using preoperative magnetic resonance images and computed tomogram images. The area of the foramen magnum was obtained independently using computer imaging software and a regression formula. The result of 21 pediatric patients was compared with a matched control group. RESULTS: The area of the foramen magnum was within the range of the expected value deduced using a formula based on the intracranial volume. There was no statistical difference in the area and linear dimensions of the foramen magnum in the study and control groups. Six patients (28%) had a foramen magnum in close proximity to a spherical shape. CONCLUSION: The authors provide a simple, accurate and reproducible method of estimating foramen magnum area in the pediatric Chiari I group. The irregular shape of the foramen magnum is accentuated by developmental bony and soft tissue anomalies at the cranio-vertebral junction in Chiari malformation. Consequently, an individualized cross-sectional assessment of the foramen magnum in relation to the hindbrain tissue in the same plane is required to study the initiation and propagation of the Chiari I symptomatology.

Dural based primary osteosarcoma in right fronto-temporal region with review of literature.

We report a case of primary dural based osteosarcoma in the right fronto-temporal convexity in a 43-year-old female who presented with a short history of seizure and headache. Radiologic evaluation revealed a well defined brightly enhancing extra-axial lesion in the right fronto-temporal region with a dural tail around the sylvian fissure. The overlying bone was uninvolved. Paraffin section of the tumor showed plump cells with moderate nuclear and cellular pleomorphism with eosinophilic extracellular material (osteiod) between the cells. At a few places, lace like osteiod was seen encasing individual cells signifying osteiod being formed by tumor cells. Immunohistochemistry for EMA was focally positive and negative for S-100 protein and GFAP. A final histopathological diagnosis of dural based primary osteosarcoma of the right fronto-temporal region was rendered. To the best of our knowledge this will be the eighth such case in literature.

Novel glioblastoma markers with diagnostic and prognostic value identified through transcriptome analysis.

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 II--diffuse astrocytoma, grade III--anaplastic astrocytoma, and grade IV--glioblastoma (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 alpha (GADD45alpha) 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 GADD45alpha and FSTL1 by immunohistochemical staining reinforced our findings. Analysis of retrospective GBM cases with known survival data revealed that cytoplasmic overexpression of GADD45alpha conferred better survival while the coexpression of FSTL1 with p53 was associated with poor survival. CONCLUSIONS: Our study reveals that GADD45alpha and FSTLI are GBM-specific whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 are primary GBM-specific diagnostic markers. Whereas GADD45alpha overexpression confers a favorable prognosis, FSTL1 overexpression is a hallmark of poor prognosis in GBM patients.

Co-existing thyrotropin secreting pituitary adenoma and low grade glioma: clinical considerations and literature review.

The authors report an extremely rare co-occurrence of a thyrotropin secreting pituitary adenoma and a low grade glioma. A 35-year old patient was initially misdiagnosed and treated as a case of primary hyperthyroidism till he presented with visual symptoms and seizures. On evaluation he was also found to have a right frontal glioma. They discuss the presentation, clinical and diagnostic implications, treatment options and possible molecular pathways which help us understand the molecular biology of such tumor associations. They review literature of 12 previous indexed reports of pituitary tumors associated with various grades of gliomas. Though there are 3 previous reports of functioning pituitary tumors and gliomas, this is the first report of a thyrotropin secreting pituitary adenoma and an associated low grade glioma.

Pseudotumor cerebri: as a cause for early deterioration after Chiari I malformation surgery.

INTRODUCTION: Chiari I malformation is associated with a small posterior fossa which cannot accommodate a growing hindbrain. Pseudotumor cerebri has been linked to developmental posterior fossa malformations. CASE REPORTS: The authors present two cases of early-deterioration post-Chiari I malformation surgery in a young and an adult patient, which were linked to raised intracranial pressure and had a stormy post-operative period. The pathophysiology of pseudotumor cerebri in early post-operative complications of Chiari malformation surgery is addressed along with arguments favoring its association. DISCUSSION: Potential clinical risk factors and red flags linking pseudotumor cerebri and Chiari malformation patients are discussed. The management of post-operative complications produced by the association is addressed.

Multiple fourth ventricular hydatidosis.

Hydatid disease caused by ingestion of eggs of the cestode Echinococcus granulosus is endemic in the Middle East, Mediterranean countries, South America, North Africa and Australia.(1) Infratentorial occurrence of hydatid cyst is rare. We present a report of an extremely rare case of multiple exclusive fourth ventricular hydatid cysts, both primary and secondary, and discuss problems with the diagnosis and management of this condition.

Persistent primitive hypoglossal artery associated with lower basilar artery aneurysm: diagnosis and clinical implications.

An elderly male was evaluated for subarachnoid hemorrhage and found to have a persistent primitive hypoglossal artery with its associated abnormal posterior fossa circulation and a lower basilar artery aneurysm. Angiography findings are described and are corroborated with computed tomography and magnetic resonance imaging. Its surgical and clinical relevance are discussed.

Serum biomarkers identification by iTRAQ and verification by MRM: S100A8/S100A9 levels predict tumor-stroma involvement and prognosis in Glioblastoma.

Despite advances in biology and treatment modalities, the prognosis of glioblastoma (GBM) remains poor. Serum reflects disease macroenvironment and thus provides a less invasive means to diagnose and monitor a diseased condition. By employing 4-plex iTRAQ methodology, we identified 40 proteins with differential abundance in GBM sera. The high abundance of serum S100A8/S100A9 was verified by multiple reaction monitoring (MRM). ELISA and MRM-based quantitation showed a significant positive correlation. Further, an integrated investigation using stromal, tumor purity and cell type scores demonstrated an enrichment of myeloid cell lineage in the GBM tumor microenvironment. Transcript levels of S100A8/S100A9 were found to be independent poor prognostic indicators in GBM. Medium levels of pre-operative and three-month post-operative follow-up serum S100A8 levels predicted poor prognosis in GBM patients who lived beyond median survival. In vitro experiments showed that recombinant S100A8/S100A9 proteins promoted integrin signalling dependent glioma cell migration and invasion up to a threshold level of concentrations. Thus, we have discovered GBM serum marker by iTRAQ and verified by MRM. We also demonstrate interplay between tumor micro and macroenvironment and identified S100A8 as a potential marker with diagnostic and prognostic value in GBM.

Rare manifestation of common disease with an unique method of minimally invasive spine stabilization: Cervical 2-3 facet lesion.

Cervical granulomatous infections of the posterior elements are very rare, it is often difficult to diagnose due to rarity and variable presentation of symptoms. Any cervical surgical procedure carries a certain morbid risk to the patient. We present a case of cervical 2-3 facet joint lesion which was managed by a minimally invasive technique with a favorable outcome.

Essential role of METTL3-mediated m6A modification in glioma stem-like cells maintenance and radioresistance.

Despite advances in biology and therapeutic modalities, existence of highly tumorigenic glioma stem-like cells (GSCs) makes glioblastomas (GBMs) invincible. N6-methyl adenosine (m6A), one of the abundant mRNA modifications catalyzed by methyltransferase-like 3 and 14 (METTL3/14), influences various events in RNA metabolism. Here, we report the crucial role of METTL3-mediated m6A modification in GSC (neurosphere) maintenance and dedifferentiation of glioma cells. METTL3 expression is elevated in GSC and attenuated during differentiation. RNA immunoprecipitation studies identified SOX2 as a bonafide m6A target of METTL3 and the m6A modification of SOX2 mRNA by METTL3 enhanced its stability. The exogenous overexpression of 3'UTR-less SOX2 significantly alleviated the inhibition of neurosphere formation observed in METTL3 silenced GSCs. METTL3 binding and m6A modification in vivo required intact three METTL3/m6A sites present in the SOX2-3'UTR. Further, we found that the recruitment of Human antigen R (HuR) to m6A-modified RNA is essential for SOX2 mRNA stabilization by METTL3. In addition, we found a preferential binding by HuR to the m6A-modified transcripts globally. METTL3 silenced GSCs showed enhanced sensitivity to γ-irradiation and reduced DNA repair as evidenced from the accumulation of γ-H2AX. Exogenous overexpression of 3'UTR-less SOX2 in METTL3 silenced GSCs showed efficient DNA repair and also resulted in the significant rescue of neurosphere formation from METTL3 silencing induced radiosensitivity. Silencing METTL3 inhibited RasV12 mediated transformation of mouse immortalized astrocytes. GBM tumors have elevated levels of METTL3 transcripts and silencing METTL3 in U87/TIC inhibited tumor growth in an intracranial orthotopic mouse model with prolonged mice survival. METTL3 transcript levels predicted poor survival in GBMs which are enriched for GSC-specific signature. Thus our study reports the importance of m6A modification in GSCs and uncovers METTL3 as a potential molecular target in GBM therapy.

Automated epileptic seizures detection using multi-features and multilayer perceptron neural network.

Detection of epileptic seizure activities from long-term multi-channel electroencephalogram (EEG) signals plays a significant role in the timely treatment of the patients with epilepsy. Visual identification of epileptic seizure in long-term EEG is cumbersome and tedious for neurologists, which might also lead to human error. Therefore, an automated tool for accurate detection of seizures in a long-term multi-channel EEG is essential for the clinical diagnosis. This study proposes an algorithm using multi-features and multilayer perceptron neural network (MLPNN) classifier. After appropriate approval from the ethical committee, recordings of EEG data were collected from the Institute of Neurosciences, Ramaiah Memorial College and Hospital, Bengaluru. Initially, preprocessing was performed to remove the power-line noise and motion artifacts. Four features, namely power spectral density (Yule-Walker), entropy (Shannon and Renyi), and Teager energy, were extracted. The Wilcoxon rank-sum test and descriptive analysis ensure the suitability of the proposed features for pattern classification. Single and multi-features were fed to the MLPNN classifier to evaluate the performance of the study. The simulation results showed sensitivity, specificity, and false detection rate of 97.1%, 97.8%, and 1 h-1, respectively, using multi-features. Further, the results indicate the proposed study is suitable for real-time seizure recognition from multi-channel EEG recording. The graphical user interface was developed in MATLAB to provide an automated biomarker for normal and epileptic EEG signals.

Multichannel EEG based inter-ictal seizures detection using Teager energy with backpropagation neural network classifier.

A long-term multichannel electroencephalogram recording plays a crucial role in recognizing the epileptic seizure activities from the brain lobes. This research study investigates the automated detection of epileptic seizures from multichannel electroencephalogram recordings using Teager energy feature. A supervised back-propagation neural network model was implemented to classify the inter-ictal seizures. The study was conducted on multichannel electroencephalogram data that was obtained from Institute of Neuroscience, Ramaiah Memorial Hospital, Bengaluru, India, after ethical clearance from the from the Institutional Ethics Board. Initially, notch filter was applied to remove the 50 Hz power line noise from raw electroencephalogram followed by independent component analysis to remove eye blinks and muscular activities. A time domain feature called Teager energy was estimated which detects the rapid changes in the given electroencephalogram time series. A 1 s windowing was introduced to ensure stationarity for estimation of Teager energy. The descriptive and box plot analysis ensures the suitability of the Teager energy for the seizure detection. The performance of the multilayer perceptron neural network classifier was evaluated using sensitivity, specificity, and false detection rate. Simulation results showed the highest sensitivity, specificity and false detection rate of 96.66%, 99.15%, and 0.30 per hour respectively. It can be concluded that procedure can be applied for real-time seizure detection.