MN1 overexpression with varying tumor grade is a promising predictor of survival of glioma patients.

Gliomas have substantial mortality to incidence rate ratio and a dismal clinical course. Newer molecular insights, therefore, are imperative to refine glioma diagnosis, prognosis and therapy. Meningioma 1 (MN1) gene is a transcriptional co-regulator implicated in other malignancies, albeit its significance in glioma pathology remains to be explored. IGFBP5 is regulated transcriptionally by MN1 and IGF1 and is associated with higher glioma grade and shorter survival time, prompting us to ascertain their correlation in these tumors. We quantified the expression of MN1, IGFBP5 and IGF1 in 40 glioma samples and examined their interrelatedness. MN1 mRNA-protein inter-correlation and the gene's copy number were evaluated in these tumors. Publicly available TCGA datasets were used to examine the association of MN1 expression levels with patient survival and for validating our findings. We observed MN1 overexpression correlated with low-grade (LGGs) and not high-grade gliomas and is not determined by the copy number alteration of the gene. Notably, gliomas with upregulated MN1 have better overall survival (OS) and progression-free survival (PFS). IGFBP5 expression associated inversely with MN1 expression levels in gliomas but correlated positively with IGF1 expression in only LGGs. This suggests a potential grade-specific interplay between repressive and activating roles of MN1 and IGF1, respectively, in the regulation of IGFBP5. Thus, MN1 overexpression, a promising predictor of OS and PFS in gliomas, may serve as a prognostic biomarker in clinical practice to categorize patients with survival advantage.

Dengue Fever Presenting with Cervicodorsal Acute Spinal Spontaneous Subdural Hematoma-Case Report and Review of Literature.

BACKGROUND: Neurologic complications are increasingly being reported in dengue epidemics. Intraspinal hematomas are rare, and those associated with dengue fever are still rarer with only 1 being reported in the literature. CASE DESCRIPTION: We report a case of dengue fever presenting with acute-onset quadriparesis (upper limbs Medical Research Council [MRC] 4/5 and lower limbs 0/5) and urinary incontinence. The patient was radiologically diagnosed with cervicodorsal acute to subacute anterior epidural hematoma. On the basis of clinical and radiologic evaluations, the patient underwent an anterior cervical approach via a split-manubriotomy, C6-D4 right anterolateral partial oblique corpectomies for evacuation of the hematoma. Intraoperatively, however, there was no evidence of anterior epidural collection and the dura revealed a bluish hue. A durotomy revealed a subdural hematoma. After evacuation of the hematoma, the patient remained paraplegic and her upper limb power worsened by MRC 1 grade. Postoperative magnetic resonance imaging revealed good evacuation and no new bleed; however, the intramedullary T2-weighted signal hyperintensities extending up to C2 persisted. She was on ventilatory support for almost 5 months. For diaphragmatic incapacity she underwent bilateral cervical phrenic nerve stimulation (diaphragmatic pacing). Despite initial improvement, she succumbed to multiple underlying comorbidities. CONCLUSIONS: Acute spontaneous spinal subdural hematoma (SSDH) is extremely rare but should be kept in mind in patients with dengue hemorrhagic fever. The radiologic findings could be deceptive and plain computed tomography and magnetic resonance imaging should be used as complementary studies to establish the diagnosis of acute spontaneous SSDH. The outcomes of SSDH are guarded, and elaborate patient counseling should be done preoperatively, keeping these in perspective.

Surpass Flow Diverter in the Treatment of Ruptured Intracranial Aneurysms-A Single-Center Experience.

BACKGROUND: Use of a Surpass flow diverter (FD) device in the treatment of acutely ruptured aneurysm has not been well studied and reported in the literature. METHODS: We retrospectively reviewed patients with subarachnoid hemorrhage who were treated by Surpass FD placement at our hospital between June 2016 and March 2018. Detailed analysis of medical records was performed to obtain patient age, gender, clinical history, Hunt and Hess grade, Fisher grade, results of radiographic and procedural details including technical success and complication, clinical outcome, and follow-up angiographic results. RESULTS: Our search identified 16 patients with 16 aneurysms who were treated with Surpass FD, of which 13 aneurysms (81%) were in the anterior circulation and 3 (19%) were in the posterior circulation. Aneurysm size ranged from 1.1 to 16 mm, with a mean of 4 mm. The mean delay between subarachnoid hemorrhage and endovascular treatment was 5 days (range, 3-20 days). Only 1 Surpass FD was used in each patient, ranging in size from 3 × 25 mm to 4 × 50 mm. Fifteen patients (94%) achieved favorable clinical outcome (modified Rankin Scale score 0-1) at 3 months. One patient died of invasive fungal infection. Angiographic follow-up results were assessed by O'Kelly-Marotta grading scale in 15 surviving patients and showed a grade D result (no filling) in 13/15 aneurysms (87%) at 3 and 6 months. CONCLUSIONS: A Surpass FD device is a feasible option for the treatment of ruptured intracranial aneurysms that are difficult to treat by conventional clipping and coiling; however, larger and comparative studies with long-term follow-up are needed to confirm its safety and efficacy.

Endovascular reconstruction of aneurysms with a complex geometry.

Conventional endovascular coiling remains the mainstay of treatment for most aneurysms; however, it may not be suitable for aneurysms with a complex geometry and there remains the risk of recanalization. Aneurysms with an unfavorable morphology are difficult to treat through both endovascular and surgical means. Progress in endovascular technology has allowed for the emergence of newer strategies to treat aneurysms with a complex geometry. Better packing density in wide-necked and large aneurysms can be achieved through the balloon remodeling technique. Similarly, a self-expanding stent cannot only act as a scaffold that helps to retain coils but also aids in diverting the blood flow away from the aneurysm sac. Lately, focus has shifted from endosaccular occlusion to endoluminal reconstruction; flow diverters are being increasingly used to treat aneurysms with an unfavorable geometry. However, there is no clear consensus on the best endovascular management strategy in certain subset of aneurysms - large and giant internal carotid aneurysms, blister aneurysms, and fusiform/dissecting aneurysms of the vertebrobasilar artery. We present a review of literature and discuss the current evidence for the various endovascular strategies to treat complex aneurysms.

Endovascular glue embolization of dissecting aneurysm of type-3 accessory middle cerebral artery: A contralateral approach.

Pediatric intracranial aneurysms are rare with a reported prevalence of 0.5-4.6%. Likewise, anomalous arterial patterns are uncommon in the cerebral circulation. Recognition of these variations and knowledge of vascular territory forms the key to managing pathological conditions associated with these anomalous vessels. Ruptured dissecting aneurysm of type-3 accessory middle cerebral artery (aMCA) has not been reported in the pediatric age group. In addition to type-3 aMCA, the child in this case report had an ipsilateral type-1 aMCA with cortical supply. We describe the patterns of accessory MCA and their vascular territory, state the perplexity involved in deciding the best management strategy, and describe the technical approach we undertook to catheterize this small caliber recurrent artery (type-3 aMCA) originating at an acute angle from the anterior cerebral artery.

Coil embolization of intracranial aneurysms with ipsilateral carotid stenosis: technical considerations.

Simultaneous occurrence of carotid atherosclerotic disease and ipsilateral cerebral aneurysm is known because of common risk factors. When interventional neuroradiologists encounter such cases, issue of 'in which order to treat these lesions ' is raised. If carotid artery disease is treated first, then acute increase in perfusion pressure and high dose antiplatelets might increase the risk of aneurysm rupture. If aneurysm coiling is performed first, the stroke risk may increase due to manipulations through plaque and compromise of cerebral flow secondary to catheter placement through stenotic vessel. Even though aneurysm coiling first is a rational approach, there are technical problems like crossing the carotid lesion safely and making sure that placement of catheter through the stenosed vessel will not compromise the cerebral blood flow. This technical report describes our protocol in performing safe and successful coil embolization in three cases with moderate carotid stenosis and ipsilateral intracranial aneurysm. Our emphasis is mainly on technical considerations with the aim of avoiding cerebral embolism during crossing of carotid plaque and to avoid compromise of cerebral blood flow using 'syngo iflow'. These technical considerations may have important implications in treatment of intracranial aneurysm in patients with moderate ipsilateral cervical carotid stenosis.

Expression of proto-oncogene KIT is up-regulated in subset of human meningiomas.

BACKGROUND: KIT is a proto-oncogene involved in diverse neoplastic processes. Aberrant kinase activity of the KIT receptor has been targeted by tyrosine kinase inhibitor (TKI) therapy in different neoplasias. In all the earlier studies, KIT expression was reported to be absent in meningiomas. However, we observed KIT mRNA expression in some meningioma cases. This prompted us to undertake its detailed analyses in meningioma tissues resected during 2008-2009. METHODS: Tumor tissues and matched peripheral blood samples collected from meningioma patients were used for detailed molecular analyses. KIT expression was ascertained immunohistochemically and validated by immunoblotting. KIT and KITLG transcript levels were discerned by reverse transcription quantitative real-time PCR (RT-qPCR). Similarly, KIT amplification and allele loss were assessed by quantitative real-time (qPCR) and validated by fluorescence in situ hybridization (FISH) on the neoplastic tissues. Possible alterations of the gene at the nucleotide level were analyzed by sequencing. RESULTS: Contrary to earlier reports, KIT expression, was detected immunohistochemically in 20.6% meningioma cases (n = 34). Receptor (KIT) and ligand (KITLG) transcripts monitored by RT-qPCR were found to co-express (p = 0.048) in most of the KIT immunopositive tumors. 1/7 KIT positive meningiomas showed allele loss corroborated by reduced FISH signal in the corresponding neoplastic tissue. Sequence analysis of KIT showed M541L substitution in exon 10, in one of the immunopositive cases. However, its biological consequence remains to be uncovered. CONCLUSIONS: This study clearly demonstrates KIT over-expression in the human meningiomas. The data suggest that up-regulated KIT transcription (p < 0.001), instead of gene amplification (p > 0.05), is a likely mechanism responsible for altered KIT expression. Thus, KIT is a potential candidate for detailed investigation in the context of meningioma pathogenesis.

A subset of human gliomas shows over-expression of KIT without its amplification.

Receptor tyrosine kinase (RTK) encoded by proto-oncogene KIT is known to be involved in different types of cancers. Reportedly, KIT expression has been associated with higher grade of gliomas. Initial RT-PCR based KIT expression observed in low grade glioma cases evoked our interest to ascertain its status in glioma patients who underwent resection during 2008-2009. Contrary to earlier reports, over-expression of the RTK was observed in 32.5% glioma cases across low/high grades (n=40). Using quantitative PCR (qPCR), an up-regulation of the receptor (KIT) and its ligand (KITLG) was detected in most of the immunopositive cases at the transcript level. Sequence analysis of KIT showed two nucleotide substitutions in exons 10 and 17, in 4 and 2 cases, respectively though their pathological significance remained unclear. qPCR detected gene amplification in 2/13 glioma and allele loss in 1/13 glioma cases. This was in accordance with FISH results of these KIT positive neoplastic tissues. The data suggest that deranged expression of KIT is independent of gene amplification (p>0.05). Aberrant KIT expression is significantly associated with transcriptional up-regulation (p<0.001), though the precise mechanism(s) for transcriptional activation remain unclear.

Ruptured intracranial aneurysm associated with von Hippel-Lindau syndrome: a molecular link?

OBJECT: Research into the etiopathogenesis of intracranial aneurysms has failed to demonstrate molecular markers or pathognomonic genetic sequences. The authors describe the case of aneurysmal rupture in a patient with von Hippel-Lindau (VHL) syndrome and explore a possible molecular link. METHODS: A 17-year-old girl underwent endovascular coiling for an aneurysmal subarachnoid hemorrhage. Six years later, she developed spinocerebellar hemangioblastomas. Gene sequencing revealed a heterozygous, germline point mutation at nucleotide 469 in the VHL locus on chromosome 3. The mutation changed a codon for proline (CCC) to one for serine (TCC) at amino acid position 86. CONCLUSIONS: The VHL tumor suppressor gene may be causally related to aneurysm formation through the effects of transcription factors, growth factors, and matrix metalloproteinases. Although a single point mutation is unlikely to be responsible for the complex phenotype of intracranial aneurysm, further research on aneurysmal domes and VHL gene expression may help validate the theory that extracellular matrix destruction is the final common pathway to aneurysm formation.