Favorable role of IDH1/2 mutations aided with MGMT promoter gene methylation in the outcome of patients with malignant glioma.

AIM: The implications of molecular biomarkers IDH1/2 mutations and MGMT gene promoter methylation were evaluated for prognostic outcome of glioma patients. MATERIALS & METHODS: Glioma cases were analyzed for IDH1/2 mutations and MGMT promoter methylation by DNA sequencing and methylation-specific PCR, respectively. RESULTS: Mutations found in IDH1/2 genes totaled 63.4% (N = 40) wherein IDH1 mutations were significantly associated with oligidendrioglioma (p = 0.005) and astrocytoma (p = 0.0002). IDH1 mutants presented more, 60.5% in MGMT promoter-methylated cases (p = 0.03). IDH1 mutant cases had better survival for glioblastoma and oligodendrioglioma (log-rank p = 0.01). Multivariate analysis confirmed better survival in MGMT methylation carriers (hazard ratio [HR]: 0.59; p = 0.031). Combination of both biomarkers showed better prognosis on temozolomide (p < 0.05). CONCLUSION: IDH1/2 mutations proved independent prognostic factors in glioma and associated with MGMT methylation for better survival.

The Description of Urodynamic Study for Bladder Dysfunction in Compressive Myelo- or Radiculo-pathy: A Prospective Study in an Institutional Setup.

PURPOSE: To study the significance of filling cystometry with pressure flow studies and bladder electromyography (EMG) in assessment and management of neurogenic bladder with myelopathies and evaluated neurological recovery in the follow-up period. METHODS: The study was a 3-year prospective urodynamic study in 63 patients, with traumatic and nontraumatic myelopathy. Bladder management was advised based on the cystometric findings. Neurological recovery and mode of bladder management were evaluated during follow-up after a minimum of 6 months. RESULTS: Mean age was 44.6 years (range 10-80 years). Thoracolumbar area was most commonly involved. Cystometry revealed overactive detrusor in 46 patients, (17 had detrusor sphincter dyssynergia [DSD], 29 without DSD) and areflexic/underactive detrusor in 9 patients. Postvoid residual (>15% of voided urine) was significant in 27 patients. Neurological recovery was seen in 60.3%, whereas 22.2% showed no improvement (partial improvement in 4.8%) and 12.6% had normal bladder function both initially and at follow-up. Correlation between neurological recovery and bladder management was found to be insignificant (P > 0.05) using spearman's correlation coefficient. CONCLUSION: Filling cystometry with pressure flow studies and EMG study is valuable for the assessment and management of neurogenic bladder in patients with myelopathy. In neurogenic bladder management and follow-up, pressure flow studies help to prevent complications and upper urinary tract complications.

Role of Diffusion and Perfusion Magnetic Resonance Imaging in Predicting the Histopathological Grade of Gliomas - A Prospective Study.

CONTEXT: Gliomas are the most common brain tumors. In addition to conventional magnetic resonance imaging (MRI) techniques, a variety of new techniques offers more than the anatomic information. The new MRI techniques include perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI). AIMS: The aim of this study is to assess the sensitivity, specificity, predictive value, and accuracy of diffusion- and perfusion-weighted MRI in the preoperative grading of gliomas. SETTING/DESIGN: The study was conducted in the Department of Neurosurgery, Pathology, and Radiodiagnosis, Sher-e-Kashmir Institute of Medical Sciences, Kashmir, India, which is the only tertiary care neurosurgical center in the state. It was a prospective study. PATIENTS AND METHODS: Thirty-one consecutive patients with gliomas were included in the study. All the patients were evaluated by a standard conventional contrast-enhanced study on Siemens 1.5 Tesla MRI. In addition to the standard MRI, diffusion- and perfusion-weighted MRI were also performed. The histopathological grading of the tumor was done as per the WHO classification of 2007. The sensitivity, specificity, predictive value, and accuracy of diffusion- and perfusion-weighted MRI in determining tumor grade were calculated. Comparison was done between PWI, DWI findings, and WHO histopathological grading. ANALYSIS METHOD: The statistical analysis was done using the Statistical Package for the Social Sciences, and receiver operating characteristic curves were used to estimate sensitivity, specificity, and accuracy. RESULTS: The overall sensitivity of PWI (with regional cerebral blood volume cutoff of 1.7) in the preoperative assessment of high-grade gliomas was 82.6% and specificity was 75%, the positive predictive value (PPV) was 90.48%, and the negative predictive value (NPV) was 60%. The overall accuracy was 80.65%. In case of DWI, the sensitivity was 69.57% and the specificity was 75%, and the PPV and NPVs were 88.8% and 46.15%, respectively. The overall accuracy was 71%. CONCLUSION: Our results clearly show higher accuracy of diffusion- and perfusion-weighted MRI in assessment of glioma grade as compared to conventional MRI. This information can prove very useful for the operating neurosurgeon in preoperative assessment and surgical planning. Postoperatively, the neuropathologist can also benefit from such information.

Endoscopic Third Ventriculostomy in Noncommunicating Hydrocephalus: Report on a Short Series of 53 Children.

INTRODUCTION: Endoscopoic third ventriculostomy (ETV) is currently considered the best alternative to cerebrospinal fluid (CSF) shunt systems in the treatment of obstructive hydrocephalus. The aim of ETV is to communicate the third ventricle with the interpendicular cistern and create CSF flow which bypasses an obstruction to the circulation of the CSF. AIMS AND OBJECTIVES: The purpose of this study was to elucidate the indications, efficacy, safety and outcome Of ETV pediatric patients of noncommunicating hydrocephalus. MATERIAL AND METHODS: This study is a 3 year prospective study from June 2012 to May 2015. Records were kept for age, gender, etilogical factors, symptoms, signs, previous use of shunt or external ventricular device, imaging findings, and surgical complications (intraoperative and postoperative). Only those patients with age between 6months and 18 years with symptoms of intracranial hypertension and radiographic evidence of noncommunicating hydrocephalus were included in the study. RESULTS: A total of 53 patients were studied, out of these 29 were boys and 24 were girls. The mean age of the patients was 6.6 years. Overall a total of 50 successful ETVs were done in 53 patients. The success rate is estimated to be 94%. There was no mortality. The average postoperative hospital stay was 4 days. The followup ranged from 6 to 16 months (mean, 12 months). CONCLUSION: ETV in children is a safe, simple and effective treatment and a logical alternative to shunting procedure for patients of noncommunicating hydrocephalus.

Clinicopathological Characteristics of Meningiomas: Experience from a Tertiary Care Hospital in the Kashmir Valley.

BACKGROUND: Meningiomas comprise 15%-20% of all primary intracranial tumors. They are generally benign tumors, and most patients are cured after surgery and remain free of recurrence. However, some tumors behave in an aggressive manner, and patients develop local recurrence or metastasis. Overall prognosis is good. PATIENTS AND METHODS: This is an 11-year retrospective study conducted in the Departments of Pathology and Neurosurgery at Sheri-I-Kashmir Institute of Medical Sciences, Kashmir, India. Besides the demographic profile, the parameters analyzed were location of tumor on imaging, histopathological subtype, and grade of tumor according to the 2007 WHO classification and recurrence at follow-up. RESULTS: A total of 254 patients were included in our study, of which 205 (80.7%) were brain meningiomas and 49 (19.3%) were spinal, with an overall female: male ratio of 2:1. Female: male ratio was more in spinal meningiomas, 15.3:1. Most of our patients were in the 4-6th decade of life with a mean age of 48 years (range: 5-73 years). Meningothelial meningioma was the most common histological type. Of ten patients who showed recurrence, seven cases showed only recurrence, but no progression to higher grade and three cases showed recurrence with progression by one WHO-grade. We also noticed that recurrence was higher in Simpson Grades II and III. CONCLUSION: Meningiomas are common in females and most of the meningiomas do well after surgery. The recurrence rate was 3.93% in our study and Simpson grade of tumor excision and histopathological grade contribute significantly to the recurrence of the tumor.

Our Experience with Management and Outcome of Isolated Traumatic Brain Injury Patients Admitted in Intensive Care Unit.

INTRODUCTION: Traumatic brain injury (TBI) is a major cause of death and disability throughout the world. Commonly used predictors of outcome both individually or in combination include age, Glasgow Coma Scale score, pupillary reactivity, early hypoxia, and hypotension. Most of the studies previously done to examine risk factors for mortality in severe TBI were done in the setting of polytrauma. AIMS AND OBJECTIVES: The aim and objective of this study was to do an in-depth analysis of various factors associated with the management and outcome of patients with isolated TBI admitted in an Intensive Care Unit (ICU). MATERIALS AND METHODS: A total of seventy adult patients who were admitted to Intensive Critical Care Unit (ICU) with isolated TBI were selected during a 12-month period from January 2016 to December 2016. This is a prospective analytical study and parameters studied included age, sex, cause of admission classified by type of trauma, premorbid functional status, acute and chronic comorbidities, brain noncontrast computed tomography scan data, Glasgow Coma Scale (GCS), hemodynamic status, respiratory status, and mechanical ventilation, blood gases, serum electrolytes, serum glucose, hemoglobin, leukocyte and platelet counts, renal function, and urinary output. RESULTS: The study population consisted of 46 (65.7%) males and 24 (34.2%) females. The mean age was 35.5 years (range, 18-65 years). The most common mode of trauma was road traffic accident (43.6%) followed by fall from height (35.7%). Statistically insignificant relationship (P < 0.05) was seen with sex and mode of injury among survivors and nonsurvivors; however, 61.9% of patients with age ≥40 years died (P < 0.005). Among clinical parameters at admission to ICU, low GCS, hypotension (mean arterial pressure ≤80 mmHg), hypoxia (pO2 ≤60 mmHg, spO2 ≤90 mmHg), and nonreacting pupils were significantly associated with increased mortality (P < 0.05). CONCLUSION: Isolated TBI still continues to have a good amount of morbidity and mortality which perhaps can be reduced by strict adherence to guidelines of management.

Primary Hypothalamic Lymphoma in an Adult Male: A Case Report and Literature Review.

Primary central nervous system lymphoma is a well-known entity. However, the hypothalamus is a rare location, especially in adults. Few cases of secondary lymphomas have been reported. We report a case of primary hypothalamic lymphoma in an adult male with normal pituitary functions. Lymphoma should be considered as one of the differential diagnosis of lesions involving the hypothalamic/third ventricular area.

Pediatric Intracranial Hydatid Cyst: A Case Series with Literature Review.

Hydatid disease is an endemic zoonotic disease in many areas of the world. An intracranial hydatid cyst is a relatively rare entity, accounting for only 1-2% of all intracranial space-occupying lesions. Most commonly they are seen in children and young adults. Here, we present 9 cases of pediatric intracranial hydatid cyst operated at Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India, between 2009 and 2015. The mean age of presentation was 11.5 years. The male to female ratio was 5: 4. In 7 cases, a history of contact with pet dogs was present. Seizure was the most common finding, present in 7 cases. Seven patients had solitary cysts and 2 had multiple cysts on presentation. All patients were operated on, and recurrence was observed in 2 patients. The features of this rare disease are retrospectively analyzed in this presentation and the literature is reviewed.

Spinal angiolipoma mimicking a schwannoma: A case report.

BACKGROUND: Angiolipomas rarely involve the spinal canal/foramina, and may prove difficult to differentiate from schwannomas. CASE DESCRIPTION: Here we report a patient who presented with a spinal angiolipoma contributing to spinal cord and neural foraminal compression that was difficult to differentiate from a schwannoma. CONCLUSION: Spinal angiolipomas rarely involve the spinal canal/foramina. Utilizing neurodiagnostic studies with pathological confirmation, these lesions may be differentiated from schwannomas.

Significant Effect of Anti-tyrosine Kinase Inhibitor (Gefitinib) on Overall Survival of the Glioblastoma Multiforme Patients in the Backdrop of Mutational Status of Epidermal Growth Factor Receptor and PTEN Genes.

INTRODUCTION: We aimed to assess the effect of anti-tyrosine kinase inhibitors (TKIs) (gefitinib) in overall survival (OS) of the glioblastoma multiforme (GBM) patients in the backdrop of mutational status of epidermal growth factor receptor (EGFR) and PTEN genes. MATERIALS AND METHODS: All the patients subjected to resection or biopsies were put on gefitinib, and radiotherapy was delivered as per the hospital protocol. EGFR and PTEN mutational spectrum was performed by single-strand conformation polymorphism followed by DNA sequencing. RESULTS: In total, 50% GBM tumors had mutation either in EGFR or PTEN. Median progression-free survival (PFS) and OS observed in patients with EGFR +ve/PTEN -ve were significantly favorable (P < 0.05) which aggregated to 9(7, 11) months and 20 (16, 24) months, respectively, than 6 (4, 8) months and 13 (7, 19) months in patients with PTEN +ve/EGFR -ve. Patients positive for both EGFR/PTEN had lower disease-free survival and OS of 6 and 9 months as compared to 6 (5, 7) and 14 (12, 24) months for those negative for both EGFR/PTEN. CONCLUSIONS: We conclude that EGFR gene alterations with wild-type PTEN are associated with significantly better PFS and OS in patients treated with anti-TKIs (gefitinib). Combined EGFR and PTEN gene mutation is associated with significantly poor response to gefitinib in terms of median OS.

WITHDRAWAL: Significant effect of anti-tyrosine kinase inhibitor (Gefitinib) on overall survival of the Glioblastoma (GBM) patients in the backdrop of mutational status of EGFR and PTEN genes.

The article by Sajad ARIF, Arshad PANDITH, Rehana TABASUM, Altaf RAMZAN, Sarabjeet SINGH, Mushtaq SIDDIQI, Abdul BHAT entitled "SIGNIFICANT EFFECT OF ANTI-TYROSINE KINASE INHIBITOR (GEFITINIB) ON OVERALL SURVIVAL OF THE GLIOBLASTOMA (GBM) PATIENTS IN THE BACKDROP OF MUTATIONAL STATUS OF EGFR AND PTEN GENES" was published ahead of print in the Journal of Neurosurgical Sciences on February 13, 2018. As corresponding author of the article, Dr. Sajad ARIF declares that he and his group submitted the same manuscript to two different journals simultaneously (Journal of Neurosurgical Sciences and Asian J Neurosurg), with subsequent redundant publications. The authors confirm their responsibility and ask for the Epub ahead of print publication of their paper in the Journal of Neurosurgical Sciences to be withdrawn. The authors deeply regret this circumstance and apologize for this misconduct to the Journal of Neurosurgical Sciences, to the Asian J Neurosurg, as well as to the readers of the journals. The corresponding author, Sajad ARIF

Supratentorial extraparenchymal schwannoma mimicking parasagittal meningioma: A rare case report.

BACKGROUND: Intracranial schwannomas not related to cranial nerves are very rare. Young age, no known history of neurofibromatosis, and seizure as initial symptom have been reported to be associated with intraparenchymal schwannoma. CASE DESCRIPTION: We report a case of supratentorial parasagittal schwannoma in the right frontal region presenting with seizure episode in a 70-year-old man. Computed tomography and magnetic resonance imaging showed a right frontal solid, enhancing extra-axial lesion based on anterior and middle third junction of superior sagittal sinus. The preoperative diagnosis was right parasagittal meningioma, however, the microscopic examination of the mass showed the characteristic pattern of cellular Antony A pattern. Immunohistocemically, the tumor stained positive for S-100 protein but negatively for epithelial membrane antigen and glial fibrillary acidic protein. These findings are consistent with schwannoma. Cysts, calcification, and peritumoral edema are common in intracerebral schwannoma, which were not seen in our case. CONCLUSION: On the basis of clinical presentation and radiological appearances, schwannoma in unusual sites can easily be mistaken for meningiomas; immunochemistry plays an important role in differentiating them. Till date, to the best of our knowledge, this is the second reported case of schwannoma mimicking meningioma in parasagittal location.

Spinal epidural abscess: Report on 27 cases.

BACKGROUND: Spinal epidural abscess, although an uncommon disease, often correlates with a high morbidity owing to significant delay in diagnosis. METHODS: In a prospective 5-year study, the clinical and magnetic resonance (MR) findings, treatment protocols, microbiology, and neurological outcomes were analyzed for 27 patients with spinal epidural abscess. RESULTS: Patients were typically middle-aged with underlying diabetes and presented with lumbar abscesses. Those undergoing surgical intervention >36 h after the onset of symptoms had poor neurological outcomes. CONCLUSION: Early recognition and timely evacuation of spinal abscesses minimized neurological morbidity and potential mortality.

Conservative management of craniovertebral junction injuries: Still a good option.

BACKGROUND: Injuries to the craniovertebral junction (CVJ) are not uncommon, and are among the few skeletal injuries that carry a high mortality rate. Successful management of these injuries depends on familiarity with the normal anatomic relationships of this region, as well as prudent decision making regarding surgical versus conservative management alternatives. METHODS: The purpose of this study was to analyze the indications for conservative treatment of CVJ trauma and to analyze the outcomes. RESULTS: Eighty-eight patients admitted with CVJ injuries were managed conservatively. More than half were nearly neurologically intact on admission; 91% improved whereas 80% (excluding deaths/lost to follow) ultimately achieved bony union without surgical intervention. CONCLUSION: This study documents that conservative management of CVJ injuries in a select population can yield good clinical results.

Surgery: Modified Pi with Triple-Bonnet Flap and Fronto-Orbital Advancement.

INTRODUCTION: Craniosynostosis is the premature fusion of one or more of the cranial sutures and can occur as part of a syndrome or as an isolated defect. Pansynostosis is a rare form of craniosynostosis that involves premature fusion of all the cranial sutures (coronal, sagittal, metopic, and occipital). Particularly in cases of late presentation, there are heightened clinical concerns, both functional and aesthetic. In untreated cases of pansynostosis and increased intracranial pressure, optic nerve damage progresses to optic atrophy and then blindness. OBJECTIVES: Cranial vault reconstruction is the standard surgical treatment. We attempt to highlight the importance of modifying the osteotomies and reshaping of the cranial vault based on individual requirements in order to achieve the best possible result and to prevent catastrophic blood loss. METHOD AND RESULTS: We present a case of modified pi with triple-bonnet flap and fronto-orbital advancement, an individual modification of the techniques of cranial vault reconstruction, in a patient with pansynostosis with optic atrophy. CONCLUSION: The technical variation can be applied to any case of pansynostosis requiring cranial vault reconstruction.

Traumatic elevated vertex fracture with delayed increase in intracranial pressure: a rare case.

INTRODUCTION: Skull fractures are traditionally classified into linear, comminuted or depressed which can either be simple or compound. A skull fracture where the bone fragment is elevated above the intact skull known as elevated skull fracture has been reported infrequently in literature. CASE PRESENTATION: We report a unique case of simple elevated vertex fracture in a 3-month-old child where the vertex had separated from the calvarium and was elevated above the level of outer table in a patient with delayed neurological deterioration. Cerebrospinal fluid leak into tight subgaleal space and gradual thrombosis of superior sagittal sinus could have led to late clinical deterioration. CONCLUSION: Prolonged monitoring, probably early repair of dural tear and aggressive management of raised ICP, is required. Reduction of fracture with careful manipulation of SSS should weigh the risk of exsanguination. No such case of an elevated vertex fracture has been reported so far in the literature.

Pediatric Head Injury: A Study of 403 Cases in a Tertiary Care Hospital in a Developing Country.

INTRODUCTION: Traumatic brain injury (TBI) in children is a significant cause of morbidity and mortality worldwide. Falls are the most common type of injury, followed by motor vehicle-related accidents and child abuse. AIMS AND OBJECTIVES: The aim and objective of this study was to elucidate the various modes of injury, prognostic factors, complications, incidence of various modes of injury, and outcome in TBI in pediatric population. MATERIALS AND METHODS: Patients with TBI, 18 years or less in age, managed in our Department of Neurosurgery, over a period of 2 years, were studied prospectively. Detailed history, general physical examination, systemic examination, and central nervous system examination including assessment of Glasgow Coma Scale score (GCS) and pupillary size and reaction were noted in every patient. Based on GCS, patients were divided into mild head injury (GCS 13-15), moderate head injury (GCS 9-12), and severe head injury (GCS ≤8) categories. All the patients were subjected to plain computed tomography (CT) scan head, and CT findings were noted. Patients were managed conservatively or surgically as per the standard indications. The outcome of all these patients was assessed by Glasgow outcome scale and divided into good (normal, moderate disability) and poor (severe, vegetative, dead) outcome. Outcome was assessed in relation to age, sex, GCS, pupil size and reaction, CT scan features, intervention, and associated injuries. RESULTS: A total of 403 patients aged between 1 day and 18 years were included in the study comprising 252 males (63%) and 151 females (37.75%). The common modes of injury were fall 228 (56.6%) followed by road traffic accidents 138 (34.2%), assault 10 (2.5%), and others 27 (6.7%) which include sports injury, hit by some object on head, and firearm injury. Majority of our patients had a GCS of 13-15 (mild head injury), 229 (57.3%), followed by 9-12 (moderate head injury) 119 (29.8%), followed by 8 or less (severe head injury) 52 (13%). In group of patients in the category of GCS ≤ 8, poor outcome was seen in 65.3%, followed by patients in group GCS 9-12 at 2.45% succeeded by group of patients with GCS 13-15 at 2.6%, which was statistically significant (P < 0.0001). A total of 354 (87.8%) patients had normal pupils, 37 (9.2%) had anisocoria, and 12 (3%) patients had fixed dilated pupils. Fixed dilated pupil had poor outcome (100%) followed by anisocoria (40.5%) and normal pupils (16%), which was statistically significant (P < 0.0001). CONCLUSION: Majority of children who suffer from TBI do well although it still continues to be a significant cause of morbidity and mortality in them. The outcome is directly related to the neurological status in which they present to the hospital.

Epidemiology of the neural tube defects in Kashmir Valley.

INTRODUCTION/BACKGROUND: Neural tube defects (NTD) are the most common congenital malformations affecting the brain and spinal cord and have a multifactorial etiology. Genetic and environmental factors have been found to cause these defects, both individually and in combination. AIMS AND OBJECTIVES: The aim of this study was to determine the incidence, types, demographics, risk factors, and other associated anomalies relevant to NTDs in Kashmir Valley. MATERIALS AND METHODS: A 2-year hospital-based prospective study was carried out from November 2013 to October 2015. A detailed history of the mother was taken along with detailed clinical examination of neonate including measurement of head circumference and checking the status of fontanella, whether - lax/full/bulging/or tense, type of NTD. Investigations that were done included were X-ray skull: Anteroposterior (AP) and lateral, X-ray spine: AP and lateral, ultrasonography abdomen, magnetic resonance imaging: Spine and brain. RESULTS: The total number of babies with NTD's was 125 with an overall incidence of 0.503. District Kupwara was having the highest incidence (1.047) and district Srinagar the lowest incidence of NTD's (0.197). The majority of NTD's (116 cases, 92.8%) were found in the rural areas. Among the different types of NTD's, spina bifida had an incidence of 0.342 (85 cases, 68%), and anencephaly had an incidence of 0.113 (28 cases, 22.4%). There was a slight preponderance of females over males with NTD's. There were70 females (56%) and 55 males (44%) respectively with a male:female ratio of 0.8:1. CONCLUSIONS: The incidence rates of NTDs are very high for Kashmir Valley. Geographical distribution of NTDs at this place confirms a relationship between the socioeconomic status, educational status, maternal age and environmental factors for the development of an NTD. The results of this study point to the importance establishing a health policy to prevent NTDs in Kashmir Valley.