Pituitary apoplexy and panhypopituitarism following acute leptospirosis.

Leptospirosis is a common tropical febrile illness which may manifest with the hepatorenal syndrome and systemic hemorrhagic manifestations. Pituitary apoplexy is a rare but life-threatening condition characterized by a hemorrhage within the pituitary gland or a pituitary adenoma. Apoplexy is very rarely associated with some inducing events such as infectious diseases such as dengue hemorrhagic fever, Hantaan virus, Puumala virus have also been reported to cause pituitary apoplexy. We present the first case of pituitary apoplexy in a patient who was being treated for leptospirosis and discuss the possible mechanisms of apoplexy in the scenario presented. We also review other reports of infectious causes that may result in pituitary apoplexy.

To be Wild or Mutant: Role of Isocitrate Dehydrogenase 1 (IDH1) and 2-Hydroxy Glutarate (2-HG) in Gliomagenesis and Treatment Outcome in Glioma.

Molecular and clinical research based on isocitrate dehydrogenase (IDH) mutations is much sought after in glioma research since a decade of its discovery in 2008. IDH enzyme normally catalyzes isocitrate to α-keto-glutarate (α-KG), but once the gene is mutated it produces an 'oncometabolite', 2-hydroxyglutarate (2-HG). 2-HG is proposed to inhibit α-KG-dependent dioxygenases and also blocks cellular differentiation. Here, we discuss the role of the IDH1 mutation in gliomagenesis. The review also focuses on the effect of 2-HG on glioma epigenetics, the cellular signaling involved in IDH1 mutant glioma cells and the therapeutic response seen in mutant IDH1(mIDH1) harboring glioma patients in comparison to the patients with wild-type IDH1. The review encompasses the debatable impacts of the mutation on immune microenvironment a propos of various mIDH1 inhibitors in practice or in trials. Recent studies revealing the relation of IDH mutation with the immune microenvironment and inflammatory status in untreated versus treated glioblastoma patients are highlighted with respect to prospective therapeutic targets. Also at the molecular level, the association of mIDH1/2-HG with the intracellular components such as mitochondria and other neighboring cells is discussed.

Pathogenesis of intracranial aneurysm is mediated by proinflammatory cytokine TNFA and IFNG and through stochastic regulation of IL10 and TGFB1 by comorbid factors.

BACKGROUND: Intracranial aneurysm (IA) is often asymptomatic until the time of rupture resulting in subarachnoid hemorrhage (SAH).There is no precise biochemical or phenotype marker for diagnosis of aneurysm. Environmental risk factors that associate with IA can result in modifying the effect of inherited genetic factors and thereby increase the susceptibility to SAH. In addition subsequent to aneurismal rupture, the nature and quantum of inflammatory response might be critical for repair. Therefore, genetic liability to inflammatory response caused by polymorphisms in cytokine genes might be the common denominator for gene and environment in the development of aneurysm and complications associated with rupture. METHODS: Functionally relevant polymorphisms in the pro- and anti-inflammatory cytokine genes IL-1 complex (IL1A, IL1B, and IL1RN), TNFA, IFNG, IL3, IL6, IL12B, IL1RN, TGFB1, IL4, and IL10] were screened in radiologically confirmed 220 IA patients and 250 controls from genetically stratified Malayalam-speaking Dravidian ethnic population of south India. Subgroup analyses with genetic and environmental variables were also carried out. RESULTS: Pro-inflammatory cytokines TNFA rs361525, IFNG rs2069718, and anti-inflammatory cytokine IL10 rs1800871 and rs1800872 were found to be significantly associated with IA, independent of epidemiological factors. TGFB1 rs1800469 polymorphism was observed to be associated with IA through co-modifying factors such as hypertension and gender. Functional prediction of all the associated SNPs of TNFA, IL10, and TGFB1 indicates their potential role in transcriptional regulation. Meta-analysis further reiterates that IL1 gene cluster and IL6 were not associated with IA. CONCLUSIONS: The study suggests that chronic exposure to inflammatory response mediated by genetic variants in pro-inflammatory cytokines TNFA and IFNG could be a primary event, while stochastic regulation of IL10 and TGFB1 response mediated by comorbid factors such as hypertension may augment the pathogenesis of IA through vascular matrix degradation. The implication and interaction of these genetic variants under a specific environmental background will help us identify the resultant phenotypic variation in the pathogenesis of intracranial aneurysm. Identifying genetic risk factors for inflammation might also help in understanding and addressing the posttraumatic complications following the aneurismal rupture.

Extraventricular neurocytoma, a comprehensive review.

AIMS AND OBJECTIVE: Extra ventricular neurocytoms (EVN) are a rare parenchymal brain tumour distinct from central neurocytomas. This review attempts to analyze a series of seven cases of EVN from a single institute against the background of available literature. METHOD: Retrospective analysis of the clinical manifestation, pathological features, imaging findings, microsurgical treatment effectiveness and progression free survival of seven cases of EVN operated between 2000-2012. RESULTS: The study group included five females and two males in the age group 7-65 years (mean 30.71 yrs). The distribution of the lesion was as follows Lobar 4, Cerebellum 1, Pineal 1, spinal 1. The duration of clinical symptoms ranged from three months to seven years and the presentation was site and size specific. Cystic Changes (71 %), perilesional oedema (57 %) and heterogeneous contrast enhancement (85.7 %), and calcification (42 %) were a few distinct imaging characteristics. Increased perfusion correlated with atypical histology in two patients. Surgical resection remains the main management strategy for longer outcome and patients with STR + RT and GTR had comparable follow-up. Extremes of age and atypical histological features were adverse prognostic factors. CONCLUSION: EVN are rare tumors with either glial or neuronal differentiation or a potential for atypical changes. Both, GTR and STR combined with RT, offer reasonably good outcome with overall comparable survival. The available literature of EVN is limited, larger series with long term follow-ups are needed to dictate the management protocol. The role of adjuvant therapy is still debatable and needs further validation.

Lack of association of lysyl oxidase (LOX) gene polymorphisms with intracranial aneurysm in a south Indian population.

Intracranial aneurysm (IA) accounts for 85 % of haemorrhagic stroke and is mainly caused due to weakening of arterial wall. Lysyl oxidase (LOX) is a cuproenzyme involved in cross linking structural proteins collagen and elastin, thus providing structural stability to artery. Using a case-control study design, we tested the hypothesis whether the variants in LOX gene flanking the two LD block, can increase risk of aSAH among South Indian patients, either independently, or by interacting with other risk factors of the disease. SNPs were genotyped by fluorescence-based competitive allele-specific PCR (KASPar) chemistry. We selected 200 radiologically confirmed aneurysmal cases and 235 ethnically and age and gender matched controls from the Dravidian Malayalam speaking population of South India. We observed marked interethnic differences in the genotype distribution of LOX variants when compared to Japanese and African populations. However, there was no significant association with any of the LOX variants with IA. This study also could not observe any significant role of LOX polymorphisms in influencing IA either directly or indirectly through its confounding factors such as hypertension and gender in South Indian population.

Multiple drug resistant bacterial biofilms on implanted catheters - a reservoir of infection.

BACKGROUND: Medical devices are an essential part of modern health-care, but its usage has led to the emergence of medical device associated infections otherwise known as Foreign-Body related infections (FBRIs). This is caused by bacterial adhesion and biofilm formation on their surfaces which act as a nidus of infection. These biofilms are resistant to antibacterial agents and host immune response. The antibiotics which are useful in treating planktonic forms cannot clear the biofilm and the device must usually be removed to resolve the infection. OBJECTIVE: The main objective of the study was to identify the prevalence of bacterial biofilms on retrieved catheters which included vascular catheters (141) and Foley catheters (86) from patients and understand the nature of antibiotic resistant strains in these biofilms. MATERIALS USED :227 numbers of retrieved catheters which included vascular catheters (141nos) and Foley catheters (86 nos) were used in the study.These retrieved implants were from patients from neurosurgery ward of SCTIMST who had undergone selective neurosurgical procedures. Patients with pre-existing infections including brain abscess were not included in the study.These patients had no clinical infection or pyrexia. Skin swabs were taken from patients using intravascular devices after retrieval of catheter. RESULTS AND CONCLUSIONS: Among vascular catheters Staphylococcus species were the major isolate and among the isolates many of the strains were Methicillin and some were Vancomycin resistant. Among the Foley catheter isolates E. faecalis was the major isolate followed by E. coli, Staphylococcus species, Klebsiella species, Pseudomonas species, Citrobacter etc. Most of the strains were resistant to multiple antibiotics. Although the patients selected did not have any clinical symptoms of infection, the presence of multiple-drug resistant organisms as biofilm points to this niche which can constitute a threat for HAls and its resultant complications. This suggests that catheters should be removed as early as possible to prevent Biofilm development on them.

Pterional Approach for Anterior Skull Base Midline Meningiomas against "The More The Merrier" Approach: An Institutional Experience.

Objective Anterior midline skull base meningiomas involving olfactory groove, planum sphenoidale, and tuberculum sellae were usually managed with bifrontal craniotomy until the dawn of advanced microsurgical techniques. With the emergence of microsurgical techniques, midline meningiomas could be tackled solely from a unilateral pterional approach. We present our experience with pterional approach in managing anterior skull base midline meningiomas, including the technical nuances and outcomes. Methods Fifty-nine patients who underwent excision of anterior skull base midline meningiomas through a unilateral pterional craniotomy between 2015 and 2021 were retrospectively analyzed. The surgical technique and patient outcomes in the context of visual, behavioral, olfaction, and quality of life were evaluated during the follow-up. Results A total of 59 consecutive patients were assessed over an average follow-up period of 26.6 months. Twenty-one (35.5%) patients had planum sphenoidale meningioma. Olfactory groove and tuberculum sellae meningioma groups consist of 19 (32%) patients each. Visual disturbance was the predominant symptom with almost 68% of patients presented with it. A total of 55 (93%) patients had complete excision of the tumor with 40 patients (68%) achieving Simpson grade II excision, and 11 (19%) patients had Simpson grade I excision. Among operated cases, 24 patients (40%) had postoperative edema among which 3 (5%) patients had irritability and 1 patient had diffuse edema requiring postoperative ventilation. Only 15 (24.6%) patients had contusion of the frontal lobe and were managed conservatively. Five patients (50%) with seizures had an association with contusion. Sixty-seven percent of patients had improvements in vision and 15% of patients had a stable vision. Only eight (13%) patients had postoperative focal deficits. Ten percent of patients had new-onset anosmia. The average Karnofsky score was improved. Only two patients had recurrence during follow-up. Conclusion A unilateral pterional craniotomy is a versatile approach for the excision of anterior midline skull base meningioma, even for the larger lesions. The ability of this approach in the visualization of posterior neurovascular structures at the earlier stages of surgery while avoiding the opposite frontal lobe retraction and frontal sinus opening makes this approach more preferable over the other approaches.

Unique presentation of occipital condyle giant cell tumor as occipital condyle syndrome - A review.

Giant cell tumors (GCTs) of the skull are rare and only a few case series with limited number of cases have been reported till date. In the cranium, GCT usually occurs in the sphenoid and temporal bone, occipital condyle GCTs are very rare. We report a rare presentation of GCT of the occipital condyle manifested as occipital condyle syndrome. Despite gross total resection, they can recur aggressively; the presence of cortical breach might be an indicator of aggressiveness prompting early post-operative imaging and adjuvant therapy.

Embryonal tumor with multilayered rosettes: Two case reports with a review of the literature.

Embryonal tumor with multilayered rosettes (ETMR) is a well-recognized histopathological variant of primitive neurectodermal tumors of the central nervous system. This tumor depicts histopathological features that are common to both ependymoblastoma (EBL) and neuroblastoma. Here we report two pediatric cases of ETMR, one exhibiting dominant neuronal differentiation and the other with dominant glial differentiation, thereby expanding the previously known pathologic spectrum. The varying histological features, common morphologic diagnostic difficulties as well as variable postsurgical survival of this entity compared to similar embryonal tumors are highlighted.

A Sporadic Cisternal Cystic Oculomotor Schwannoma-Case Report and Review of Literature.

Schwannoma arising from a pure motor cranial nerve in sporadic cases is a rare finding. We report adult female patient presented with a seizure without oculomotor palsy. On evaluation, she was diagnosed with cystic oculomotor schwannoma and underwent surgery. She developed oculomotor palsy postoperatively. Here, we describe a rare sporadic cystic oculomotor schwannoma.

Endoscopic Endonasal Excision of a Complex Craniopharyngioma Operated Multiple Times by Transcranial Route.

Background: Complex craniopharyngiomas pose a significant surgical challenge owing to its proximity to critical structures and its intrinsic nature to resist radical excision. Objective: To show that endoscopic endonasal approach (EEA) is potentially a better alternative to transcranial approach in tumors that have been operated multiple times by transcranial route for achieving radical excision with minimal morbidity. Materials and Methods: A 32-year-old male previously operated twice through interhemispheric approach for craniopharyngioma presented with blurring of vision accompanied by headache and intermittent diplopia. Imaging revealed a large lobulated suprasellar recurrence with a large calcified part adjacent to left internal carotid artery. The tumor was resected by an extended endonasal approach. The patient experienced improvement in his vision with no significant endocrine complication. Results and Conclusion: This case demonstrates the surgical technique and various operative nuances of endoscopic endonasal resection of a complex craniopharyngioma.

Endoscopic Endonasal Excision of a Ventral Exophytic Brainstem Glioma: A Technical Case Report.

BACKGROUND AND IMPORTANCE: Ventral midbrain glioma is an extremely rare lesion in adults. The endoscopic endonasal approach is potentially a better alternative to transcranial approach for this challenging lesion and has not been described in the literature. CLINICAL PRESENTATION: A 22-yr-old woman previously operated through an interhemispheric approach for ventral midbrain glioma with extension in the suprasellar cistern presented with severe headache and diplopia. Imaging revealed an increase in size of the residual lesion. The tumor was resected by using an extended endonasal approach. The patient had improvement in her diplopia with no endocrine complication. CONCLUSION: This case demonstrates the surgical technique of endoscopic endonasal resection of a ventral midbrain glioma.

Endoscopic Endonasal Excision of a Meckel's Cave Dermoid Cyst.

Background: Meckel's cave dermoid cyst is an extremely rare and a technically challenging lesion. The objective of the study is to show that endoscopic endonasal approach (EEA) has recently emerged as a better alternative to transcranial approach for this formidable tumor, owing to minimal retraction-related morbidity. Method: A 52-year-old male presented with numbness over the right side of the face and temporal area for the last 3 years. On examination, there was decreased sensation to touch, pain, and temperature over the right V1, V2, and V3 areas with an absent right corneal reflex. Imaging revealed a heterogenous extra-axial lesion in the right Meckel's cave. The tumor was resected by an extended endonasal transpterygoid approach. Results: The patient had improvement in his symptoms with no endocrine complication. Conclusion: This case demonstrates the surgical techniquenof endoscopic endonasal transpterygoid resection of a Meckel's cave dermoid cyst.

Glioblastoma with primitive neuronal component: An immunohistochemical study and review of literature.

Glioblastoma with primitive neuronal component, a rare neoplasm, is recognized as a distinct histological pattern of glioblastoma. In this study we report the morphological and immunohistochemical features of three cases of glioblastoma with primitive neuronal component diagnosed at the Institute along with a comprehensive literature review. The cases include: (1) 11-year-old girl with right fronto-parietal lesion, (2) 48-year-old male with right parietal lesion, and (3) 36-year-old male with left fronto-parietal lesion. Case 1 had prior history of glioblastoma. All the cases had classic morphology of glioblastoma along with GFAP-negative and synaptophysin-positive primitive neuronal component. The latter was poorly demarcated from the glial component in case 1, while well-defined in the remaining two. All the three cases exhibited diffuse p53 positivity and a higher MIB-1 labelling index in the neuronal component compared to the glial component. One of them (case 3) was IDH1 R132H-mutant with loss of ATRX expression. None were positive for K27M-mutant H3 or G34R-mutant H3.3. Literature review of 50 published cases of glioblastoma with primitive neuronal component was performed. The age of onset ranged from 3 months to 82 years (mean: 50 years) with M:F of 1.5:1. 18.8% of tumors were IDH-mutant, 87.5% were p53 positive and three cases showed H3F3A gene mutations. There was a greater propensity for neuraxial dissemination, noted in 20% of cases. Overall survival of glioblastoma with primitive neuronal component was similar to that of IDH-wildtype glioblastoma (13 months) which was significantly shorter compared to the overall survival of IDH-mutant glioblastoma (33.6 months).

Simultaneous trigonal and spinal meningioma with varied histology: A rare case report.

BACKGROUND: Meningioma is one of the most common neoplasms of the central nervous system. Multiple meningiomas without neurofibromatosis are not a usual occurrence. Intraventricular meningioma with spinal meningioma is rare and not been reported in the literature. CASE DESCRIPTION: We report a case of a 63-year-old male with the left trigonal and spinal meningioma. Both the meningiomas were resected in different settings. The histological examination of tumors revealed to be of varied histology, that is, meningothelial and atypical meningioma, respectively. CONCLUSION: Although various cases with multiple cranial and spinal meningiomas are described, this is the first case of an intraventricular and spinal meningioma. With varied histology, the case also reaffirms the theory of polyclonal origin of multiple meningiomas.

MutT Homolog1 has multifaceted role in glioma and is under the apparent orchestration by Hypoxia Inducible factor1 alpha.

AIMS: The study focused on the expression and role of a recent potential cancer therapeutic target protein, MutT Homolog1 (MTH1). MTH1 gets activated in an increased reactive oxygen species (ROS) environment and removes the oxidized nucleotides from the cell. The study aimed to check the role of MTH1 in DNA damage and apoptosis, migration and angiogenesis and also to examine its regulation in glioma. MAIN METHODS: The experiments were carried out in human glioma tissue samples and brain tissues of epilepsy patients (non-tumor control). We used two human glioblastomas cell lines, U87MG and U251MG cells. In order to study the role of MTH1 in glioma and to analyze the relation of MTH1 with Hif1α, we have used MTH1 siRNA and Hif1α siRNA respectively. KEY FINDINGS: We found an increased expression of MTH1 in glioma tissues compared to the non-tumor brain tissues. Correlation analysis revealed that those samples showing reduced expression of MTH1 also had high levels of DNA damage and apoptotic markers, while diminished expression of angiogenesis regulators and levels of migration. MTH1 knockdown in vitro by siRNA in tumor cell lines corroborates the above observation. This justifies the emergence of MTH1 inhibitors as potential first-in-class drugs. Mechanistically, our observations suggest that Hif1α may modulate MTH1 expression. SIGNIFICANCE: We found elevated MTH1 expression in glioma irrespective of their grades, while its inhibition affects multiple tumor progression pathways, and that targeting Hif1α could simulate the same.