Clinicohistoradiological and surgical outcome in diffuse midline glioma.

PURPOSE: Diffuse Midline Glioma (DMG) with H3K27M mutation is a rare and aggressive midline high grade glioma with a predominant astrocytic differentiation and K27M mutation in either H3F3A or HIST1H3B/C. This tumor is more common in children than in adults. The current study was aimed to determine clinicohistoradiological and surgical outcome of patients who have undergone surgery for DMG and study disease severity of patients with DMG. METHODS: This is an observational study in which 29 DMG patients were evaluated for clinicohistoradiological and surgical outcomes by assessing the pre and postoperative neurological status. RESULT: Survival duration was significantly high in patients with age > 18 years (p = 0.02). Patients who had undergone Radiation Therapy showed higher survival rate (p = 0.05) and the cases with low levels of Ki 67 index had improved post operative outcome (p = 0.002). CONCLUSION: DMG with H3K27M mutation in newly classified Central Nervous System tumor are WHO grade IV Tumors, comprising H3K27M mutation as molecular marker for diagnosis and related with a poor prognosis.

Clinicomorphological and molecular analysis of medulloblastoma and association with survival: A single tertiary care center experience.

BACKGROUND: Medulloblastoma (MB) is a heterogeneous disease, displaying distinct genetic profiles, with specific molecular subgroups. Various clinical, pathological and molecular variables have been associated with disease outcome and therefore utilised in risk stratification of patients. OBJECTIVES: To perform molecular classification of medulloblastoma using surrogate immunohistochemistry (IHC) and associate molecular subgroups, histopathological types, and available clinicopathological parameters with overall survival (OS) of MB patients. RESULTS: This study included 65 medulloblastoma patients. Immunohistochemical staining, using ß-catenin YAP1 and GRB2-Associated Binding Protein 1 (GAB1) antibodies was used to classify MB cases into wingless signalling (WNT) activated, sonic hedgehog (SHH) activated, and non-WNT/non-SHH molecular subgroups. The relevant statistical analysis was done using GraphPad Prism version 9.3.0. Histological patterns included classic (40 cases, 62%), desmoplastic nodular (D/N) (14 cases, 22%), large cell/anaplastic (LC/A) (9 cases, 13%), medulloblastoma with extensive nodularity (MBEN) (1 case, 1.5%) and one special subtype, i.e., medulloblastoma with myogenic and melanotic differentiation. Molecular subgroups included WNT (4 cases, 6%), SHH (34 cases, 52%), and non-WNT/non-SHH (27 cases, 42%) subgroups. Histopathological types differed significantly according to tumor location, degree of anaplasia and molecular subgroups. Molecular subgroups differed significantly in age distribution and tumor location. The probability of survival was 78% and 68% after 1 and 2 years, respectively. Infants (<3 years of age), LC/A pattern, and TP53-mutant status among SHH subgroup conferred poor prognosis in our study. At the end of the study (at 65 months of maximum follow-up period) probability of survival was 51%. CONCLUSIONS: Immunohistochemical analysis helps in molecular classification of medulloblastoma in majority of the cases as well as helps in predicting prognosis and treatment response.

Will you choose neurosurgery as your career? An Indian female medical student perspective.

OBJECTIVE: We aim at recognising the reasons that discourage female medical students to consider neurosurgery as a career, from an Indian perspective. METHODOLOGY: An online survey was disseminated in various medical colleges of India. The study included female medical students (both cis and trans). The questionnaire consisted of objective questions on mentorship, opportunities and exposure. Their concerns on long working hours and the reasons for the same were recorded. RESULTS: 348 responses were included of which 79.9 % of students felt they didn't receive proper exposure to neurosurgery in their medical school. 87.4 % of the respondents faced a lack of opportunity and mentorship for research. 65.2 % of students felt that they would be more interested in neurosurgery if a female professor were to mentor them. Long working hours and Reduced Family and Personal time were identified as statistically significant factors (p < 0.001) that play a role in demotivating female medical students towards neurosurgery. Altered quality of life was the most frequent (79.49 %) and significant reason (p = 0.004) as to why long working hours were a concern for them. 65.07 % of participants did not consider physical strength to be a hurdle (p = 0.008). Approximately 37.6 % participants felt that maternity and neurosurgery could be incompatible (p = 0.005). CONCLUSIONS: The study brings out the notions that female medical students have regarding the long working hours and decreased family and personal time, complicated by pregnancy and maternal leave in the life of female neurosurgeon.

Clinical Profile, Pathology, and Molecular Typing of Gliomas with Oligodendroglial Morphology: A Single Institutional Experience.

Background: Diffuse gliomas are represented in the 2007 WHO classification of CNS tumors as astrocytomas, oligoastrocytoma, and oligodendroglioma of grades II/III and glioblastomas WHO grade IV, which was a pure morphologic classification. WHO 2016 classification combines morphology with molecular markers like IDH, ATRX, and 1p/19q codeletion to give an integrated diagnosis. Methods: The study was carried out on formalin fixed paraffin embedded tissues from 54 patients including three pediatric patients. Molecular studies were performed to know the 1p/19q codeletion status, IDH1R132H, and ATRX immunoexpression. Also, the IDH1R132H status was correlated with survival data. Results: The study included 54 tumors with oligodendroglial morphology. IDH1R132H positivity was seen in 85% of total cases and codeletion was seen in 72%. The integrated diagnosis revised the cases into oligodendroglioma (39), astrocytoma (5), and glioblastoma (6).IDH mutant tumors were found to have better survival than negative ones which was statistically significant. Conclusion: This study emphasizes the need for molecular work up of tumors with oligodendroglial morphology with readily available techniques like IHC and Fluorescence in situ hybridization.

Subarachnoid Hemorrhage and Hydrocephalus.

BACKGROUND: Hydrocephalus associated with subarachnoid hemorrhage is a common neurosurgical problem, the management of which is tailor-made to the patient. It is usually seen with an aneurysmal bleed and is independent of the primary modality of treatment. AIM: This study aimed to provide a comprehensive overview of this important association and discuss the various available treatment modalities. MATERIALS AND METHODS: A detailed review of the literature was done on the risk factors, pathogenesis, and treatment of hydrocephalus in the setting of subarachnoid hemorrhage. RESULTS: Hydrocephalus occurs in 6% to 67% of subarachnoid hemorrhage (SAH). It may present as acute, subacute, or chronic at the time of presentation. Diagnosis is made with a plain computed tomography scan of the brain, and the treatment is observant, temporary, or permanent cerebrospinal fluid diversion. CONCLUSION: Hydrocephalus associated with SAH interferes with the outcome of SAH. It prolongs the hospital stay, besides causing additional morbidity. The various risk factors, if present, should warn us to be vigilant, and management is definitely not uniform and is custom made to the patients' needs.

Indian Society of Pediatric Neurosurgery Consensus Guidelines on Preventing and Managing Shunt Infection: Version 2020-21.

BACKGROUND: Shunt infection is the most significant morbidity associated with shunt surgery. Based on the existing literature for the prevention and management of shunt infection, region and resource-specific recommendations are needed. METHODS: In February 2020, a Guidelines Development Group (GDG) was created by the Indian Society of Paediatric Neurosurgery (IndSPN) to formulate guidelines on shunt infections, which would be relevant to our country and LMIC in general. An initial email survey identified existing practices among the membership of the IndSPN, and eight broad issues pertaining to shunt infection were identified. Next, members of the GDG performed a systematic review of the literature on the prevention and management of shunt infection. Then, through a series of virtual meetings of the GDG over 1 year, evidence from the literature was presented to all the members and consensus was built on different aspects of shunt infection. Finally, the guidelines document was drafted and circulated among the GDG for final approval. Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to grade the evidence and strength of recommendation. RESULTS: The guidelines are divided into eight sections. Level I and Level II evidence was available for only five recommendations and led to a moderate level of recommendations. Most of the available evidence was at Level III and below, and hence the level of recommendation was low or very low. A consensus method was used to provide recommendations for several issues. CONCLUSIONS: Although most of the recommendations for the prevention and management of shunt infections are based on a low level of evidence, we believe that this document will provide a useful reference to neurosurgeons not only in India but also in other low and middle income countries. These guidelines need to be updated as and when new evidence emerges.

A Rare Complication of Pituitary Adenoma Surgery in a Patient with Multiple Endocrine Neoplasia 1 Syndrome with Two Novel Genetic Mutations.

Pituitary adenoma surgeries are common in neurosurgical setup. Majority are tackled by a transsphenoidal route either by endoscopic or microscopic aid. Complications such as cerebrospinal fluid (CSF) leak, meningitis, diabetes insipidus, hematoma, and loss of vision are known, but midbrain infarct is rarely reported. We report and discuss the possible mechanism of this rare and unusual complication in transsphenoidal surgery. A 36-year-old nulliparous female with no comorbidities suffering from primary infertility presented with intermittent headache for 9 months with bitemporal vision disturbances for 3 months, pigmentation around the neck and nape, oligomenorrhea with an established diagnosis of plurihormonal secreting pituitary tumor (predominantly adrenocorticotropic hormone and prolactin), hyperparathyroidism, and diabetes. The whole symptom fitted into the diagnosis of multiple endocrine neoplasia 1 (MEN-1) syndrome. Molecular genetic testing was done with full gene sequencing analysis of MEN-1 gene using polymerase chain reaction. Furthermore, Sanger DNA sequencing was done, and two novel variations, namely IVS 9c.1364 + 99C>G and EXON 10 c.1813 C>T (p. L605 L), were detected. Radiology detected a microadenoma in the right lobe of the pituitary with mild deviation of the pituitary stalk on dynamic contrast-enhancing magnetic resonance imaging. Gross total excision of the tumor was done through transsphenoidal approach. The surgery was uneventful other than some blood-mixed CSF leak. Post excision, fat and tissue glue was packed. The patient did not wake up from anesthesia and had bilateral dilated pupil with no oculocephalic reflex. Investigations revealed bilateral thalamic and midbrain infarct. The patient subsequently expired. This case is reported in view of its unusual complication and to create awareness for such a fatal complication following transsphenoidal surgery for pituitary microadenoma and the importance of diligent approach to transsphenoidal surgery and to report novel genetic mutation of MEN-I gene.

A clinicopathologic study of surgically resected metastatic lesions of brain: A single institutional experience.

INTRODUCTION: One of the most common tumors of the brain are metastatic lesions. They can present as cancer of unknown primary (CUP) and require careful determination of the site of origin of the primary. Histopathologic and immunohistochemical analysis helps to determine the primary site. AIM: To study the clinicopathological features of metastatic tumors of the brain. MATERIALS AND METHODS: All cases of surgically resected brain metastasis (solid tumor metastasis) from January 2013 to April 2015 were included in the study. The clinical details including age, gender, clinical features, and location were taken from medical records. The histopathology slides were retrieved and reviewed along with clinical and imaging findings from medical records. Immunohistochemistry was performed wherever necessary. RESULTS: Out of 1662 resected brain lesions during the study period, 69 accounted for central nervous system metastasis, of which 36 were brain metastasis and 33 were isolated spinal cord metastasis. In the 36 brain metastasis cases, 19 were cases with an unknown primary. Carcinoma lung (47.2%) was found to be the most common primary malignancy. Immunohistochemistry with cytokeratin (CK)7, CK20, and thyroid transcription factor (TTF) 1 as a primary panel in metastatic tumors is highly recommended. CONCLUSION: Metastatic tumors accounted for 4.1% of intracranial lesions. Histopathologic pattern and immunohistochemistry aid in the accurate diagnosis of the original site of malignancy.

A Series of Biopsy-proven Patients with Immunoglobulin G4-related Neurological Disease.

AIM: To study the clinical presentation, radiological findings, and therapy responsiveness of patients with biopsy-proven immunoglobulin G4 (IgG4)-related neurological disease. METHODS: The study was conducted between January 2016 and March 2018 from the Department of Neurology and Pathology of Nizam's Institute of Medical Sciences. Patients with neurological symptoms and biopsy suggestive of IgG4-related disease (IgG4-RD) were included. These patients were studied for their demographic pattern and clinical presentation. The presence of serological markers such as vasculitic profile and IgG4 levels was analyzed. Radiological findings were studied in detail. Therapeutic agents used and the response to therapy were assessed. RESULTS: There were six cases with IgG4-related neurological disease which were all hypertrophic pachymeningitis. The age ranged from 35 to 64 (mean = 46) years. The clinical presentation was acute in one, subacute in two, and chronic in three patients. The most common presenting symptom was headache (4), followed by gait and/or urinary disturbances (2), paraparesis (1), and diplopia (1). IgG4 levels were elevated in 50% of them. Pseudotumor-like mass and sinovenous thrombosis, not described previously, were seen in one patient. All the patients were treated with oral or intravenous steroid. Rituximab was given in three patients; azathioprine was the steroid-sparing agent in one patient. Those with acute/subacute onset of presentation had an excellent response to steroids. All the patients with a chronic duration of their symptoms received empirical anti-tuberculous therapy before a definitive diagnosis of Ig G4-RD was made. CONCLUSIONS: The characterization of patients with IgG4-related neurological disease based on the understanding of the clinical spectrum increases the confidence in the clinician to resort to early immunosuppression, thereby having prognostic implications.

Atypical location of unusual supratentorial neurenteric cyst: a case report.

We report a case of a right anterior clinoid process (ACP) neurenteric cyst which presented with gradual impairment of vision in the right eye. Imaging suggested an infective cystic lesion. In view of rapid visual loss urgent surgery was conducted. Erosion of the ACP was found from where white mucus like material was aspirated. The cyst wall was completely excised. Immunohistochemistry indicated an endodermal origin of the cyst.

Skull and Spinal Ewing's Sarcoma in Children: An Institutional Study.

BACKGROUND: Ewing's sarcoma is a disease of children and young adults and occurs most often in bone and soft tissues. The intracranial and spinal manifestation of the disease is rare and reported incidence is 1%-6%. AIMS AND OBJECTIVES: We conducted this study to determine the surgical outcome of children with skull and spine Ewing's sarcoma (SSES). METHODS: This is a prospective analysis of 13 patients of SSES who reported to the Department of Neurosurgery, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India, between 2014 and 2016. All cases after detailed examination, magnetic resonance imaging, and computed tomography scan were subjected to surgery followed by adjuvant therapy comprising chemotherapy and radiotherapy. Outcome was analyzed at 6 months as well at latest follow-up. Neurological function, local recurrence, primary or secondary nature of the disease, distant relapse, and treatment-related complications were analyzed in this study. RESULTS: There were eight female and five male patients with a mean age of 12 years (ranging from 4 to 8 years). Pain was the common presenting feature in all cases. Focal neurological deficits corresponding to the anatomical location was seen in six patients. These 13 cases were distributed anatomically as four cases involving the cloves, two cases with occipital bone and lobe involvement, one case of parietal bone and lobe involvement, and six cases of spinal involvement. Surgery was performed in all cases where gross total excision (Ozge C, Calikoglu M, Cinel L, Apaydin FD, Ozgür ES. Massive pleural effusion in an 18-year-old girl with Ewing sarcoma. Can Respir J 2004;11:363-5), near-total excision, and subtotal excision was achieved in these 13 cases (Steinbok P, Flodmark O, Norman MG, Chan KW, Fryer CJ. Primary Ewing's sarcoma of the base of the skull. Neurosurgery 1986;19:104-7). Subsequently all cases underwent multiagent chemoradiotherapy. Postsurgery pain subsided in 12 (92%) of patients. Ten patients maintained or improved motor function. In seven cranial cases and in six spinal cases, four cases showed improvement whereas three (23%) had deterioration of motor function. CONCLUSIONS: Surgical outcome of SSES in short-term follow-up is good with current recommended management regimen of maximum excision followed by chemo and radiotherapy. However, metastasis is not uncommon.

Junctional Chiasmatic Syndrome Due to Large Anterior Communicating Artery Aneurysm.

Even though aneurysm involving the anterior communicating artery (A Com A) was common in clinical practice, producing compressive symptoms such as visual loss was rare. We report a case, in which patient had gradually progressive visual loss with features of the junctional chiasmatic syndrome, imaging revealed partially thrombosed large A Com A aneurysm. Intraoperatively, aneurysm was found compressing the optic chiasm and right optic nerve, following clipping and decompression of the optic nerve and chiasm there was gradually improvement in the vision over 2 weeks postoperatively.

Vascular malformations of central nervous system: A series from tertiary care hospital in South India.

AIMS AND OBJECTIVES: To describe clinicopathological features of surgically resected vascular malformations (VMs) of central nervous system (CNS). MATERIALS AND METHODS: Histologically diagnosed cases of VMs of CNS during April 2010-April 2014 were included. Demographic data, clinical and radiological features were obtained. Hematoxylin and eosin slides were reviewed along with Verhoeff-Van Gieson (VVG), Masson's trichrome, periodic acid-Schiff, and Perls' stains. Morphologically, cavernomas and arteriovenous malformations (AVMs) were distinguished on the basis of vessel wall features on VVG and intervening glial parenchyma. RESULTS: Fifty cases were diagnosed as VMs of CNS with an age range of 14-62 years. These included 36 cavernomas, 12 AVMs, 2 mixed capillary-cavernous angiomas. Most of the cavernoma patients (15/36) presented with seizures, whereas AVM patients (8/12) had a headache as the dominant symptom. Twenty-nine patients were reliably diagnosed on radiological features. Microscopic evidence of hemorrhage was seen in 24/36 cavernomas and 6/12 AVMs, as opposed to radiologic evidence of 10 and 4, respectively. Reactive gliosis was seen in 16 cavernomas. CONCLUSIONS: Histological features are important for classifying the VMs of CNS as there are no specific clinical and radiological features. Type of VM has a bearing on management, prognosis, and risk of hemorrhage.

Craniosynostosis in a child with I-cell disease: The need for genetic analysis before contemplating surgery in craniosynostosis.

We are reporting a rare case of I-cell disease presenting with craniosynostosis. An 11-month-old child presented with abnormal head shape, developmental delay and bent bones. We planned for corrective surgery for craniosynostosis, but on genetic analysis I-cell disease was confirmed. After explaining the prognosis of I-cell disease, parents denied surgery. This case report emphasizes the fact that syndromic evaluation of craniosynostosis is very much essential before proceeding for corrective surgery.

Importance of C1 laminectomy in foramen magnum decompression surgery: A technical note.

Arnold-Chiari malformations (ACM) of the brain result from aberrations in the development of the posterior fossa resulting in its smaller volume leading to tonsillar herniation. The most common type includes Type I ACM where tonsillar descent reaches up to either C1 or C2 along with cervico-dorsal syringomyelia. The surgery (foramen magnum decompression, [FMD]) is usually straight forward and includes sub-occipital craniectomy and cervical laminectomy based on the level of descent. Rarely inadequate cervical laminectomy of C1 arch may result in residual compression at the level of obex even after "lax" duraplasty. A cervico-dural angle (angle between the neo-dura and cervical dura) at level foramen magnum can be observed in these patients. This angle is usually obtuse in imaging of cranio-vertebral junction (CVJ) of normal people and in postoperative patients of Chiari malformations where normal anatomy is restored. Inadequate C1 laminectomy may result in an acute cervico-dural angle with residual compression at the level of CVJ. Therefore, C1 laminectomy becomes a key step in FMD surgery that is often underemphasized, and neurosurgeons should be careful in doing it adequately.

A novel case of "ambulatory" cervical spondyloptosis: case report with literature review.

BACKGROUND: Cervical spondyloptosis is an extreme variant of cervical spinal injury where patients usually present with disabling neurological deficits. Presentation of these patients without significant morbidity is very rare and we could only find sporadic case reports in literature involving traumatic cervical spondyloptosis without neurological deficits. Usually such patients get spared due to expansion of spinal canal after fracture of posterior vertebral elements. We report a case of traumatic C5/C6 spondyloptosis in an ambulatory patient despite having an intact posterior vertebral arch. This patient was managed successfully with anterior cervical fusion. CONCLUSION: To the best of our knowledge, this is the first case report of its kind as it exemplifies the rarity of such an occurrence and underlines the importance of timely management to maintain such preserved neurological status.

Outcome of supratentorial intraaxial extra ventricular primary pediatric brain tumors: A prospective study.

INTRODUCTION: Tumors of the central nervous system (CNS) are the second most frequent malignancy of childhood and the most common solid tumor in this age group. CNS tumors represent approximately 17% of all malignancies in the pediatric age range, including adolescents. Glial neoplasms in children account for up to 60% of supratentorial intraaxial tumors. Their histological distribution and prognostic features differ from that of adults. AIMS AND OBJECTIVES: To study clinical and pathological characteristics, and to analyze the outcome using the Engel's classification for seizures, Karnofsky's score during the available follow-up period of minimum 1 year following the surgical and adjuvant therapy of supratentorial intraaxial extraventricular primary pediatric (SIEPP) brain tumors in children equal or less than 18 years. MATERIALS AND METHODS: The study design is a prospective study done in NIMS from October 2008 to January 2012. All the patients less than 18 years of age operated for SIEPP brain tumors proven histopathologically were included in the study. All the patients with recurrent or residual primary tumors or secondaries were excluded from the study. Post operative CT or magnetic resonance imaging (MRI) is done following surgery. RESULTS AND ANALYSIS: There were 2, 8 and 20 patients in the age range of 0-2 years, >2-10 years and 10-18 years, respectively. There were 21 male patients and 9 female patients. Out of 30 patients, 16 had lesion in the temporal lobe, 6 in frontal lobe, 4 in thalamus, 3 in parietal lobe and 1 in occipital lobe. Out of 30 patients, 11 patients had malignant lesions and nineteen patients had benign lesions. Gross total excision could be achieved in 19 patients and subtotal in 11 patients. Seven patients had mortality and four of the remaining 23 patients had increased deficits postoperatively. Remaining 19 patients either improved or remained same. CONCLUSIONS: SIEPP brain tumors have male preponderance, occur in 95% of patients in the age range of 7-18 years and have temporal lobe as the most common site of origin. The seizure presentation has good outcome compared to raised intracranial pressure features. The seizure control is quite good irrespective of subtotal or gross total excision in temporal lobe low grade tumors. All PNETs have survival of less than 1 year even with adjuvant chemo and radiotherapy.