Search

Surgical outcome predictive models for Chiari malformations (CM) which are applicable to all age groups and simple enough to use on outpatient basis are lacking.The aim of this study was to develop and validate a preoperative index for predicting long-term outcomes in Chiari 1 (CM1) and Chiari 0 (CM0) malformations.It was a single-institution, ambidirectional, cohort study from 2014 to 2019, having patients between 5 to 70 years. Outcome was assessed using Chicago Chiari outcome score (CCOS) over 2 years follow-up. Preoperative clinical and radiological factors were analyzed using Chi-square test and Mann Whitney U test, in relation to CCOS and those attaining P value ≤0.05, were used to develop model - Chiari Outcome Predictive Index (COPI). COPI was internally validated using 10-fold cross-validation and c-statistic for discrimination.A total of 88 patients (66 in development and 22 in validation cohort) were included in the study. Outcome was negatively associated with presence of motor, sensory or cranial nerve symptoms, poor functional status, basilar invagination, and tonsillar descent. It was positively associated with shorter duration of presenting symptom (9 months) and syrinx diameter6 mm. COPI predicted CCOS with 91.1% accuracy (10-fold cross-validation). It had excellent discrimination for improved outcome (c = 0.968 in development and 0.976 in validation cohort), at threshold index of -1.COPI is simple tool that can be administered in outpatient setting. It can facilitate evidence-based preoperative counseling of patients, to help them develop reasonable expectations regarding surgical outcomes.

Gliomas are heavily infiltrated with immune cells of myeloid origin. Past studies have shown that high-grade gliomas have a higher proportion of alternatively activated and suppressive myeloid cells when compared to low-grade gliomas, which correlate with poor prognosis. However, the differences in immune cell phenotypes within high-grade gliomas (between grade III and IV) are relatively less explored, and a correlation of phenotypic characteristics between immune cells in the blood and high grade tumors has not been performed. Additionally, myeloid cells of granulocytic origin present in gliomas remain poorly characterized. Herein, we address these questions through phenotypic characterizations of monocytes and neutrophils present in blood and tumors of individuals with glioblastoma (GBM, grade IV) or grade III gliomas. Our data show that CD163 expressing M2 monocytes are present in greater proportions in GBM tissue when compared to grade III glioma tissue. In addition, we observe that neutrophils are highly heterogeneous among individuals with glioma, and a greater proportion of granulocytic myeloid-derived suppressor cells are present in grade III gliomas when compared to GBM. Finally, we show that the expression levels of CD86 and CD63 showed a high correlation between blood and tumor, and suggest that these may be used as possible markers for prognosis.

Craniofacial resection is the technique of choice for tumors of the oral cavity or paranasal sinus extending close to the skull base of middle cranial fossa. Here we would like to describe a new technique of approaching these tumors through the facial incision itself. All patients treated with this technique at our institute were included in this retrospectively analyzed case series. The pathological clearance margins, complications and outcomes were studied. A total of nine patients underwent resection of tumor with the subcranial approach. There were seven males and two female patients. Mean age was 50.66 years (22–72 years). The diagnosis was squamous cell carcinoma in five patients, adenoid cystic carcinoma in three patients and alveolar soft part sarcoma in one patient. A lip split incision and mandibulotomy/mandibulectomy was done in seven patients; a Weber–Fergusson incision was used in one patient and details were not available in one other patient. Reconstruction was done with anterolateral thigh flaps with or without titanium mesh for all the patients. One patient developed thalamic infarct and was managed conservatively. None of the other patients had complications related to the craniotomy. The infratemporal fossa margin was close/involved in two patients (22.22%). Eight patients received adjuvant therapy without delay. One patient, who had received radiation previously, did not receive adjuvant radiation. This technique aims to reduce morbidity without compromising on the oncological outcomes for tumors extending short of or up to the skull base.

Splice variants are known to be important in the pathophysiology of tumors, including the brain cancers. We applied a proteogenomics pipeline to identify splice variants in glioblastoma (GBM, grade IV glioma), a highly malignant brain tumor, using in-house generated mass spectrometric proteomic data and public domain RNASeq dataset. Our analysis led to the identification of a novel exon that maps to the long isoform of Neural cell adhesion molecule 1 (NCAM1), expressed on the surface of glial cells and neurons, important for cell adhesion and cell signaling. The presence of the novel exon is supported with the identification of five peptides spanning it. Additional peptides were also detected in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel separated proteins from GBM patient tissue, underscoring the presence of the novel peptides in the intact brain protein. The novel exon was detected in the RNASeq dataset in 18 of 25 GBM samples and separately validated in additional 10 GBM tumor tissues using quantitative real-time-polymerase chain reaction (qRT-PCR). Both transcriptomic and proteomic data indicate downregulation of NCAM1, including the novel variant, in GBM. Domain analysis of the novel NCAM1 sequence indicates that the insertion of the novel exon contributes extra low-complexity region in the protein that may be important for protein-protein interactions and hence for cell signaling associated with tumor development. Taken together, the novel NCAM1 variant reported in this study exemplifies the importance of future multiomics research and systems biology applications in GBM.

Diffuse astrocytoma (DA; WHO grade II) is a low-grade, primary brain neoplasm with high potential of recurrence as higher grade malignant form. We have analyzed differentially expressed membrane proteins from these tumors, using high-resolution mass spectrometry. A total of 2803 proteins were identified, 340 of them differentially expressed with minimum of 2 fold change and based on ≥2 unique peptides. Bioinformatics analysis of this dataset also revealed important molecular networks and pathways relevant to tumorigenesis, mTOR signaling pathway being a major pathway identified. Comparison of 340 differentially expressed proteins with the transcript data from Grade II diffuse astrocytomas reported earlier, revealed about 190 of the proteins correlate in their trends in expression. Considering progressive and recurrent nature of these tumors, we have mapped the differentially expressed proteins for their secretory potential, integrated the resulting list with similar list of proteins from anaplastic astrocytoma (WHO Grade III) tumors and provide a panel of proteins along with their proteotypic peptides, as a resource that would be useful for investigation as circulatory plasma markers for post-treatment surveillance of DA patients.

Temporary diversion of cerebrospinal fluid (CSF) is often required due to patient and CSF related factors, of which infection is a significant one. The various methods available have significant disadvantages. Ventriculosubgaleal shunts (VSG) have been earlier demonstrated to be useful in a variety of circumstances.Hospital charts of 21 consecutive children during a 4-year period were analyzed retrospectively. Infection was defined based on a positive CSF culture or a history of recently treated meningitis with abnormal CSF findings. The conversion to a permanent shunt was based on normalization of CSF values in a functioning VSG shunt or when the VSG shunt is ineffective. The end point was control of raised intracranial pressure (ICP) features and infection.The ages ranged from 1 month to 7 years with a median age of 2 months. Five (23.8%) were born premature. Twelve children (57.1%) had a previously untreated hydrocephalus, whereas nine (42.8%) had undergone some procedure. A positive CSF culture was obtained in ten (47.6%). Repeat VSG shunts were required in five children (23.8%). Seventeen (80.9%) of these children underwent conversion to a ventriculoperitoneal (VP) shunt. Of the remaining four, one did well without any further procedure, two died due to their primary problems, and one refused any further procedure due to poor neurological status. There were two wound complications-one CSF leak and one shunt migration.VSG shunts are a simple and efficient way of managing infective hydrocephalus.