The Role of Single-Nucleotide Polymorphisms in Pituitary Adenomas Tumorigenesis

Pituitary adenomas (PAs) are among the most common intracranial neoplasms, but despite their histologically benign nature, these tumors sometimes grow large enough to cause symptoms of mass effect such as vision loss, headaches, or hypopituitarism. When they get this large, surgery will unfortunately not be curative and, other than prolactinomas, medical options are limited, and radiation has variable efficacy in controlling growth. Understanding the genetic perturbations, such as single nucleotide polymorphisms (SNPs), that promote the formation or growth of functional and nonfunctional PAs is important because such genetic insights could improve the diagnosis and subsequent classification of PAs as well as unlock potential therapeutic targets outside contemporary standard of care. While there have been great strides in the research of SNPs as drivers of PA formation and maintenance, a comprehensive discussion of these genetic mutations has not been undertaken. In the present article, and with the goal of providing scientists and clinicians a central review, we sought to summarize the current literature on SNPs and their relationship to PA formation. Across multiple tumor types, such as nonfunctioning PAs, prolactinomas, corticotroph adenomas, somatotroph adenomas, thyrotropic adenomas, and gonadotroph adenomas, SNPs in cell surface receptors implicated in proliferation can be appreciated. Polymorphisms found in tumor suppressors and cell cycle regulators have also been identified, such as p53 SNPs in nonfunctioning PAs or cyclin D1 in prolactinomas. While the translational relevance of SNPs in the formation of PAs is still in the early stages, the use of wide-scale genomic analysis to identify patients at risk for developing PAs could yield therapeutic benefit in the future

Treatment of Cerebral Vasospasm in an Infant Using a Modified Dotter Technique

An 8-month old female presented with spontaneous subarachnoid hemorrhage and was treated successfully with endovascular coil embolization of the ruptured aneurysm. Transcranial Doppler ultrasound performed four days later demonstrated middle cerebral artery (MCA) velocities greater than 350 cm/sec on the right and greater than 200 cm/sec on the left, despite medical management. The patient demonstrated no focal neurological deficits, though examination was limited by our patient's sedation and intubation. Angiography revealed severe vasospasm of the supraclinoid internal carotid and MCA territories, bilaterally. The vasospasm was refractory to the administration of intra-arterial verapamil. Balloon angioplasty was attempted, but the device could not be advanced safely due to the small size of the patient's vessels and the stiffness of the device. A microcatheter (0.0165" diameter) was advanced over a J-shaped soft microwire (0.014" diameter) to perform mechanical angioplasty in the internal carotid artery and MCA vessels bilaterally. Dramatic improvement was seen angiographically and on transcranial Doppler, and no complications were seen

Treatment of adult and pediatric high-grade gliomas with Withaferin A: antitumor mechanisms and future perspectives

Resistance mechanisms employed by high-grade gliomas allow them to successfully evade current standard treatment of chemotherapy and radiation treatment. Withaferin A (WA), utilized in Ayurvedic medicine for centuries, is attracting attention for its antitumor capabilities. Here we review pertinent literature on WA as a high-grade glioma treatment, and discuss the cancerous mechanisms it affects. WA is relatively nontoxic and has shown potential in crossing the blood-brain barrier. WA prevents p53 alterations and inactivates overexpressed MDM2 through ARF and ROS production. Furthermore, WA upregulates Bax, inducing mitochondrial death cascades, inhibits mutated Akt, mTOR, and NF-κB pathways, and inhibits angiogenesis in tumors. Therapy with WA for high-grade gliomas is supported through the literature. Further investigation is warranted and encouraged to fully unearth its abilities against malignant gliomas

Epidemiology and etiology of secondary piriformis syndrome: A single-institution retrospective study

•Pelvic neoplasms can compress the sciatic nerve, causing secondary PS.•Neoplastic compression of sciatic nerve accounted for 20% of PS.•Pelvic imaging should be considered in patients with non-spinal sciatica. Piriformis syndrome (PS) is a rare etiology of extra-spinal sciatica in which pathologies associated with or around the piriformis muscle (PM) irritate the adjacent sciatic nerve (SN), however, there is scarcity in the literature regarding its exact etiologies, thus, we performed a retrospective study to elucidate the epidemiology of PS and assess various causes of the syndrome. Our study included patients assessed at our institution who presented with sciatica of non-spinal origin between May 2014 and December 2015. Radiology reports of all patients who received pelvic MRI were examined for positive findings involving PM and SN. Of the 143 patients recognized with sciatica and negative lumbar pathology, 24 patients (17%) exhibited positive PM and SN findings. Average patient age was 50.0 ± 15.1 years (range: 21–75), and 17 were female. Seven patients (5%; 4M/3F) presented with tumor, seven patients (5%) had chronic inflammatory changes, one patient had SN adhesions to obturator muscle, three patients (2%, 3F) had aberrant anatomy, and the remaining patients had positive MRI findings, such as nerve atrophy or PM hypertrophy without identifiable cause. Seven patients received steroid injections in the peri-sciatic fossa, and four displayed poor response. Our findings suggested possible trends in extra-spinal sciatica. Affected males appeared more likely to present with tumor, while affected females were more likely to present younger, but with aberrant anatomy. Steroid injections appeared to be suboptimal in most cases. Pelvic MRI is helpful in patients with sciatica and negative spine imaging to rule out neoplastic involvement

Investigating the therapeutic role and molecular biology of curcumin as a treatment for glioblastoma

Objectives: Despite the aggressive standard of care for patients with glioblastoma multiforme, survival rates typically do not exceed 2 years. Therefore, current research is focusing on discovering new therapeutics or rediscovering older medications that may increase the overall survival of patients with glioblastoma. Curcumin, a component of the Indian natural spice, turmeric, also known for its antioxidant and anti-inflammatory properties, has been found to be an effective inhibitor of proliferation and inducer of apoptosis in many cancers. The goal of this study was to investigate the expanded utility of curcumin as an antiglioma agent. Methods: Using the PubMed MeSH database, we conducted a systematic review of the literature to include pertinent studies on the growth inhibitory effects of curcumin on glioblastoma cell lines based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 19 in vitro and five in vivo studies were analyzed. All of the studies indicated that curcumin decreased glioblastoma cell viability through various pathways (i.e. decrease in prosurvival proteins such as nuclear factor κB, activator protein 1, and phosphoinositide 3 kinase, and upregulation of apoptotic pathways like p21, p53, and executor caspase 3). Curcumin treatment also increased animal survival compared with control groups. Conclusions: Curcumin inhibits proliferation and induces apoptosis in certain subpopulations of glioblastoma tumors, and its ability to target multiple signaling pathways involved in cell death makes it an attractive therapeutic agent. As such, it should be considered as a potent anticancer treatment. Further experiments are warranted to elucidate the use of a bioavailable form of curcumin in clinical trials

Scalp congenital hemangioma with associated high-output cardiac failure in a premature infant: Case report and review of literature

INTRODUCTION: Scalp congenital hemangiomas (CHs) are rare vascular malformations among infants; they can be associated with an array of complications, including cardiac and cosmetic issues. Here, we report the endovascular treatment of a premature infant with a suspected large right parietal scalp hemangioma and associated high-output cardiac failure. CASE DESCRIPTION: A two-day-old female premature infant (29 weeks gestational age; 1330 g birth weight) was referred by the neonatologists to our department for consultation and potential treatment of a large right parietal CH causing abrupt hypotension and high-output cardiac failure. Doppler ultrasound imaging at bedside revealed areas of arterial-venous shunting from the scalp and the presence of a superior sagittal sinus waveform, consistent with intracranial venous drainage. To alleviate cardiac dysfunction secondary to this lesion, trans-arterial embolization via n-butyl cyanoacrylate (nBCA) glue and deployment of detachable coils was performed via umbilical artery to occlude the right superficial temporal and occipital artery branches supplying the CH. Following treatment, the infant continued to require ventilator management, vasopressor support, and correction of coagulopathy, but by post-operative day two, her condition improved remarkably and the mass size began decreasing. The patient was discharged after a relatively uncomplicated subsequent 2½-month course in the neonatal intensive care unit. CONCLUSION: Endovascular therapy proved effective and safe in treating cardiac failure associated with scalp CH, despite potential complications associated with neuro-interventional surgery in premature infants. Appropriate consideration in this patient population should be given to factors including blood loss, contrast use, radiation exposure, operative time, and possible intra-/post-operative complications

Current applications and future perspectives of robotics in cerebrovascular and endovascular neurosurgery

Advances in robotic medicine have been adopted by various surgical subspecialties as the benefits of this technology become more readily apparent: precision in narrow operative windows, tremor controlled movements, and modestly improved outcomes, among others. Vascular neurosurgery, in particular, remains open to newer and more cutting edge treatment options for complex pathologies, and robotics may be on the horizon for such advances. We seek to provide a broad overview of these innovations in vascular neurosurgery for both practitioners well acquainted with robotics and those seeking to become more familiar. Technologies under development for cerebrovascular and endovascular neurosurgery include robot assisted angiography, guided operative microscopes, coil insertion systems, and endoscopic clipping devices. Additionally, robotic systems in the fields of interventional cardiology and radiology have potential applications to endovascular neurosurgery but require proper modifications to navigate complex intracerebral vasculature. Robotic technology is not without drawbacks, as broad implementation may lead to increased cost, training time, and potential delays in emergency situations. Further cultivation of current multidisciplinary technologies and investment into newer systems is necessary before robotics can make a sizable impact in clinical practice