EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) POLYMORPHIC VARIATIONS (-216G/T & -191 C/A) POSE A HIGH RISK TO PATIENTS WITH MALIGNANT GLIOMA.

BACKGROUND: Malignant gliomas are the most frequent and lethal brain tumors. Their molecular aspects remain intangible but current studies have pointed to certain genetic polymorphic loci that pose the risk. The polymorphic sequence variations of the epidermal growth factor receptor gene (EGFR) pathway play a vital role in the glioma risk, and the EGFR variants (216G>T and 191C>A) are identified to affect the risk for the development of different tumors including glioma. AIM: To examine genetic variations of EGFR T rs712829 (216G/T) and rs712830 (191C>A) with respect to glioma risk. MATERIALS AND METHODS: 129 confirmed glioma cases were genotyped against 180 malignancy-free healthy controls by polymerase chain reaction-restriction fragment length polymorphism technique (RFLP). RESULTS: The frequency of the TT homozygous variant of the EGFR -216 G/T genotype differed significantly between cases and controls (49.6% vs. 23.0%) (p < 0.0001). The EGFR -216 G>T allele 'T' was found significantly more frequently in cases (0.56 vs. 0.33 in controls; p < 0.0001). The EGFR -191C>A homozygous 'AA' genotype was implicated significantly more frequently in cases than in controls (p < 0.0001). The distribution of the 'A' variant allele was also more frequent in cases (41.9%) than in controls (14.0%) (0.55 vs. 0.30; p < 0.0001). TC and TA haplotypes showed varied frequency in cases and controls. CONCLUSION: EGFR -216 G>T and -191 C>A variants and haplotypes (TA and TC) of the EGFR gene are very strong risk factors in the development of glioma in the Kashmiri population.

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.

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.

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.

Epidemiology of the neural tube defects in Kashmir Valley.

BACKGROUND: Neural tube defects (NTDs) 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. METHODS: A 2-year hospital-based prospective study was carried out from November 2013 to October 2015 to determine the incidence, types, demographics, risk factors, and other associated anamolies relevant to NTDs in Kashmir Valley. 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: Anterior-posterior (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. Kupwara district was having the highest incidence (1.047) and Srinagar district the lowest incidence of NTD's (0.197). 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 were 70 females (56%) and 55 males (44%), respectively, with a male: female ratio of 0.8:1. CONCLUSIONS: The incidence rates of NTDs is very high for Kashmir Valley. Geographical distribution of NTDs at this place confirms a relationship between the socioeconomic status, educational status, maternal too young or advanced age, and environmental factors for the development of a NTD. The results of this study point to the importance establishing a health policy to prevent NTD in Kashmir Valley.

Vertex epidural hematoma with bilateral abducent nerve palsy: case report and literature review.

Epidural hematomas which are located at the vertex are rarely seen and form a small percentage of total epidural hematomas. Tearing in the superior sagittal sinus is the usual cause of an epidural hematoma located in the vertex. The clinical features of this entity are non-specific; hence, localization of the lesion is difficult. We report an adult who was hit by a motorcycle and was initially discharged from the hospital as a case of concussional head injury. He returned back with raised intracranial pressure symptoms, so a CT scan was done but was misinterpreted, and he reported one week later with bilateral abducent nerve palsy. Magnetic resonance imaging confirmed vertex EDH for which he was operated.These hematomas are seen rarely and can be interpreted as an artifact. Its recognition is important because it has an excellent prognosis. We concluded that all head injury patients should get high axial cuts on the CT scan, and any degree of suspicion should prompt a neurosurgeon to investigate further with coronal CT scan or MRI.

Atypical localizations of hydatid disease: experience from a single institute.

INTRODUCTION: The hydatid disease most often involves the liver and the lungs. The disease can involve any part of the body except the hair, teeth and nails. Primary extrahepatico-pulmonary hydatid cysts are rare and only a few sporadic cases have been reported. MATERIALS AND METHODS: Two hundred and forty-four patients with hydatid cysts managed surgically from January 2005 to December 2009 were evaluated retrospectively. Fourteen (5.7%) patients had isolated involvement of the atypical sites, while six (2.4%) also had a primary involvement of liver. RESULTS: The cysts were present in gall bladder (0.4%), peritoneum (1.6%), spleen (1.6%), ovary (0.4%), subcutaneous (0.8%), seminal vesicle (0.4%), spinal (0.4%), pancreas (0.4%), kidney (0.4%), mediastinal (0.4%), muscle (0.4%), and brain (0.8%). DISCUSSION AND CONCLUSIONS: Involvement of sites other than liver and lungs by hydatid disease is rare. Symptoms are related to size, location or possible complication of the cyst. It should be strongly suspected in differential diagnosis of all abdominal cysts especially in an endemic area. Proper surgical and medical management to avoid any recurrences, and a regular follow-up, are of utmost importance to detect any late complications such as local recurrence of the disease and development of hydatidosis at the primary sites.

Hypodensity of extradural hematomas in children: an ominous sign.

OBJECT: The aim of this study was to analyze the correlation of hypodensity in extradural hematomas on CT with the clinical profile in pediatric patients. This is the only study available in this age group. METHODS: This was a prospective study conducted over a period of 3 years in which all children 18 years old or younger with a diagnosis of cranial extradural hematoma were included. The patients were allocated to 2 groups: those with mixed-density clots (17 cases) and those with classically hyperdense clots (52 cases). A comparative analysis between the 2 groups was conducted. RESULTS: Patients with mixed-density clots presented earlier to the hospital, had poor Glasgow Coma Scale scores at admission, exhibited large clot volumes, had a high incidence of active bleeding at surgery, and had increased morbidity and mortality as compared with the patients with hyperdense extradural hematomas. CONCLUSIONS: Early recognition and rapid evacuation of the mixed-density clot with restoration of hemostasis may result in a decline in morbidity and death in children with this entity.

Role of albendazole in the management of hydatid cyst liver.

BACKGROUND/AIM: Hydatidosis has a worldwide distribution and the liver is the most common organ involved. Hydatid cysts of the liver can be managed either by nonoperative or operative methods. Nonoperative methods include chemotherapy and percutaneous treatment. The study aimed at understanding the effect of albendazole therapy on the viability of protoscoleces and recurrence rate of hydatid disease of the liver. PATIENTS AND METHODS: The study was conducted at Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India, over a period of 2 years from January 2002 to December 2003, with further follow-up of 5 years. The study included 72 cases in the age group of 17-66 years, comprising 39 males and 33 females. The patients were randomized into two groups of 36 patients each. In group A, patients were directly subjected to surgery, while in group B, patients were administered albendazole for 12 weeks preoperatively, followed by a further postoperative course for 12 weeks. RESULTS: Of patients who received albendazole therapy, no patient had viable cysts at the time of surgery, as compared to 94.45% of the patients who did not receive any preoperative albendazole (P<0.01). In patients who did not receive any albendazole therapy, recurrence rate was 16.66%, while no recurrence was seen in patients who received albendazole therapy (P≤0.05). CONCLUSION: We conclude that albendazole is an effective adjuvant therapy in the treatment of hydatid liver disease.

Gluteal pseudophallus in a male child: A rare cutaneous marker of occult spinal dysraphism.

Congenital midline paraspinal cutaneous markers have been practically linked to the location and nature of neural-tissue lesions. One of the most interesting congenital midline paraspinal cutaneous markers has been the human tail in the lumbosacral region, with underlying spinal dysraphism. Human tails have many shapes and sizes and are usually localized to the lumbosacral region. After a complete neurological examination, the MRI is the most sensitive diagnostic modality to reveal the underlying occult spinal dysraphic state. Surgical excision is aimed at untethering of the spinal cord in symptomatic children and for aesthetic reasons in asymptomatic patients. Here we report an asymptomatic male child with normal external genitilia, whose tail is attached to the gluteal region like an adult phallus and investigations revealed an underlying spinal dysraphic state.

Surgeon and human immunodeficiency virus infection.

HIV infection has attained extraordinary attention among surgeons and other health care workers as a potential source of occupational infection. Disease is usually blood-borne and transmissible, and due to the nature of surgical work, surgical community has become involved and is developing sterile surgical barriers, and improved surgical techniques and procedures.

Albendazole as an adjuvant to the standard surgical management of hydatid cyst liver.

BACKGROUND: The treatment options for hydatid cyst liver include non-operative and operative methods. Operative methods include conservative and radical procedures. Non-operative methods include chemotherapy and percutaneous treatment of liver hydatidosis. MATERIAL AND METHODS: The study was conducted at Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India, over a period of two years from March 2001 to February 2003 with further follow-up of 5-6 years. The study included 64 cases in the age group of 15 years to 64 years, comprising 36 males and 28 females. The aim of the study was to know the effect of preoperative and postoperative albendazole therapy on the viability of protoscolices and recurrence rate of hydatid disease of liver. Patients were divided into four group of 16 each. In group A, patients were directly subjected to surgery. In group B, patients were given albendazole for 8 weeks followed by surgery. In group C, patients were given albendazole for 8 weeks preoperatively followed by further postoperative course for 8 weeks. In group D, patients were first taken for surgery followed by postoperative course of albendazole for 8 weeks. RESULTS: Out of those patients who received preoperative albendazole only 9.37% had viable cysts at the time of surgery as compared to 96.87% of patients who did not receive any preoperative albendazole. In those patients who did not receive any albendazole therapy, recurrence rate was 18.75% whereas recurrence was 4.16% in patients who received albendazole therapy. CONCLUSION: We conclude that albendazole is safe and effective adjuvant therapy in the treatment of hydatid liver disease.