Synergetic neuroprotection of normobaric oxygenation and ethanol in ischemic stroke through improved oxidative mechanism.

BACKGROUND AND PURPOSE: Normobaric oxygenation (NBO) and ethanol both provide neuroprotection in stroke. We evaluated the enhanced neuroprotective effect of combining these 2 treatments in a rat stroke model. METHODS: Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 hours. Reperfusion was then established and followed by treatment with either (1) an intraperitoneal injection of ethanol (1.0 g/kg), (2) NBO treatment (2-hour duration), or (3) NBO plus ethanol. The extent of brain injury was determined by infarct volume and motor performance. Oxidative metabolism was determined by ADP/ATP ratios, reactive oxygen species levels, nicotinamide adenine dinucleotide phosphate oxidase activity, and pyruvate dehydrogenase activity. Protein expression of major nicotinamide adenine dinucleotide phosphate oxidase subunits (p47(phox), gp91(phox), and p67(phox)) and the enzyme pyruvate dehydrogenase was evaluated through Western immunoblotting. RESULTS: NBO and ethanol monotherapies each demonstrated reductions as compared to stroke without treatment in infarct volume (36.7% and 37.9% vs 48.4%) and neurological deficits (score of 6.4 and 6.5 vs 8.4); however, the greatest neuroprotection (18.8% of infarct volume and 4.4 neurological deficit) was found in animals treated with combination therapy. This neuroprotection was associated with the largest reductions in ADP/ATP ratios, reactive oxygen species levels, and nicotinamide adenine dinucleotide phosphate oxidase activity, and the largest increase in pyruvate dehydrogenase activity. CONCLUSIONS: Combination therapy with NBO and ethanol enhances the neuroprotective effect produced by each therapy alone. The mechanism behind this synergistic action is related to changes in cellular metabolism after ischemia reperfusion. NBO plus ethanol is attractive for clinical study because of its ease of use, tolerability, and tremendous neuroprotective potential in stroke.

Neuroprotection conferred by post-ischemia ethanol therapy in experimental stroke: an inhibitory effect on hyperglycolysis and NADPH oxidase activation.

Ethanol provides neuroprotection following ischemia/reperfusion. This study assessed ethanol's effect on hyperglycolysis and NADPH oxidase (NOX) activation. Adult, male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Three sets of experiments were conducted to determine ethanol's effect on (i) conferring neuroprotection by measuring infarct volume and neurological deficits 24 h post reperfusion; (ii) cerebral glucose metabolism and lactic acidosis by measuring brain and blood glucose concentrations and protein expression of glucose transporter 1 and 3 (GLUT1, GLUT3), phosphofructokinase (PFK), as well as lactic acidosis by measuring lactate dehydrogenase (LDH), and lactate; and (iii) nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activation by detecting enzymatic activity and subunit expression at 3 h after reperfusion. When administered upon reperfusion, ethanol (1.5 g/kg) reduced infarct volume by 40% (p < 0.01) and neurological deficits by 48% at 24 h post reperfusion while reducing (p < 0.01) elevations in glycolytic protein expression and lactate levels during early reperfusion (3 h). Ethanol increased the reductions in cerebral glucose concentration at 3 h post reperfusion by 64% (p < 0.01) while enhancing (p < 0.01) post stroke blood glucose concentration, suggesting a reduced cellular glucose uptake and utilization. Ethanol decreased (p < 0.01) stroke-induced NOX activation by reducing enzymatic activity and gp91(phox) expression by 45% and 38%, respectively. Post-ischemia ethanol treatment exerts neuroprotection through attenuation of hyperglycolysis and associated NOX activation. Because of the lack of associated hypoglycemia and selectivity toward decreasing cerebral metabolism, further investigation of ethanol's use as a post-stroke therapy, especially in the context of hyperglycemia, seems warranted.

Preischemic exercise reduces brain damage by ameliorating metabolic disorder in ischemia/reperfusion injury.

Physical exercise preconditioning is known to ameliorate stroke-induced injury. In addition to several other mechanisms, the beneficial effect of preischemic exercise following stroke is due to an upregulated capacity to maintain energy supplies. Adult male Sprague-Dawley rats were used in exercise and control groups. After 1-3 weeks of exercise, several enzymes were analyzed as a gauge of the direct effect of physical exercise on cerebral metabolism. As a measure of metabolic capacity, an ADP/ATP ratio was obtained. Glucose transporters (GLUT1 and GLUT3) were monitored to assess glucose influx, and phosphofructokinase (PFK) was measured to determine the rate of glycolysis. Hypoxia-induced factor-1α (HIF-1α) and 5'AMP-activated protein kinase (AMPK) levels were also determined. These same analyses were performed on preconditioned and control rats following an ischemic/reperfusion (I/R) insult. Our results show that GLUT1, GLUT3, PFK, AMPK, and HIF-1α were all increased following 3 weeks of exercise training. In addition, the ADP/ATP ratio was chronically elevated during these 3 weeks. After I/R injury, HIF-1α and AMPK were significantly higher in exercised rats. The ADP/ATP ratio was reduced in preconditioned rats in the acute phase after stroke, suggesting a lower level of metabolic disorder. GLUT1 and GLUT3 were also increased in the acute phase in exercise rats, indicating that these rats were better able to increase rates of metabolism immediately after ischemic injury. In addition, PFK expression was increased in exercise rats showing an enhanced glycolysis resulting from exercise preconditioning. Altogether, exercise preconditioning increased the rates of glucose metabolism, allowing a more rapid and more substantial increase in ATP production following stroke.

Post-operative diabetes insipidus after endoscopic transsphenoidal surgery.

Diabetes insipidus (DI) after endoscopic transsphenoidal surgery (ETSS) can lead to increased morbidity, longer hospital stays, and increased medication requirements. Predicting which patients are at high risk for developing DI can help direct services to ensure adequate care and follow-up. The objective of this study was to review our institution's experience with ETSS and determine which clinical/laboratory variables are associated with DI in this patient population. The authors wanted to see if there was an easily determined single value that would help predict which patients develop DI. This represents the largest North American series of this type. We retrospectively reviewed the charts of patients who had undergone ETSS for resection of sellar and parasellar pathology between 2006 and 2011. We examined patient and tumor characteristics and their relationship to postoperative DI. Out of 172 endoscopic transsphenoidal surgeries, there were 15 cases of transient DI (8.7%) and 14 cases of permanent DI (8.1%). Statistically significant predictors of postoperative DI (p < 0.05) included tumor volume and histopathology (Rathke's cleft cyst and craniopharyngioma). Significant indicators of development of DI were postoperative serum sodium, preoperative to postoperative change in sodium level, and urine output prior to administration of 1-deamino-8-D-arginine vasopressin. An increase in serum sodium of ≥2.5 mmol/L is a positive marker of development of DI with 80% specificity, and a postoperative serum sodium of ≥145 mmol/L is a positive indicator with 98% specificity. Identifying perioperative risk factors and objective indicators of DI after ETSS will help physicians care for patients postoperatively. In this large series, we demonstrated that there were multiple perioperative risk factors for the development of DI. These findings, which are consistent with other reports from microscopic surgical series, will help identify patients at risk for diabetes insipidus, aid in planning treatment algorithms, and increase vigilance in high risk patients.

Synchronous meningioma and anaplastic large cell lymphoma.

Synchronous primary brain tumors are exceedingly rare. When they occur, most cases are associated with metastatic disease. To the best of our knowledge, we report the first case of an atypical meningioma infiltrated by a T-cell-primary central nervous system lymphoma (PCNSL), specifically anaplastic large cell lymphoma (ALCL). We present a novel, unifying, plausible mechanism for its origin based on theories in the current literature. A 65-year-old man with a history of near-total resection of atypical meningioma presented with a complaint of progressive headaches. Imaging revealed recurrent tumor. Left frontal-temporal craniotomy with near-total tumor resection followed by radiation was performed. Recurrent symptomatic tumor led to repeat left frontotemporal craniotomy with tumor resection and partial anterior temporal lobectomy. Part of the specimen showed predominantly fibrotic neoplasm composed of nests and whorls of meningothelial cells, highlighted by epithelial membrane antigen (EMA) staining. The remainder of the specimen consisted of densely cellular neoplasm centered in connective tissue, including areas involved by meningioma. This tumor was composed of moderately large lymphoid cells with large nuclei, prominent nucleoli, and amphophilic cytoplasm. These cells were strongly immunoreactive for CD3 and CD30 but remained unstained with EMA, anaplastic lymphoma kinase-1 (ALK-1), CD15 or cytotoxic associated antigen TIA-1. Smaller mature lymphocytes, chiefly T-cells, were intermixed. The morphologic and immunohistochemical features were considered typical of anaplastic large T-cell lymphoma. The pathogenesis of this association may have been due to radiation-mediated breakdown of the blood-brain barrier with subsequent T-cell infiltration and proliferation. We advocate aggressive resection and long-term surveillance for individuals with metastasis, especially higher-grade neoplasms that receive radiotherapy.

Non-Langerhans cell histiocytosis with isolated CNS involvement: an unusual variant of Erdheim-Chester disease.

Benign histiocytic proliferations are identified by their component cells and classified as either Langerhans cell histiocytosis or non-Langerhans cell histiocytosis. We report a 58-year-old Caucasian woman who presented with diabetes insipidus and was found to harbor a large suprasellar mass. Histopathological analysis was consistent with non-LCH. The differential diagnoses included juvenile xanthogranuloma, adult-onset xanthogranuloma, xanthoma disseminatum, Rosai-Dorfman disease, and Erdheim-Chester disease. Immunohistochemical examination demonstrated a proliferation of large lipid-laden histiocytic cells which were positive for CD68, negative for S100 protein, and showed only faint, background staining for CD1a. We present a case of an autopsy-confirmed non-Langerhans cell histiocytosis limited to the central nervous system and evaluated with both immunohistochemical and ultrastructural studies. Based on the multifocality, anatomic distribution, and immunostaining features, a diagnosis of Erdheim-Chester disease was made. This is only the second reported case of Erdheim-Chester disease with intracranial involvement but absence of extracerebral manifestations. Given the overlapping clinicopathologic, radiographic, and immunohistochemical profiles, differentiating between these rare histiocytic disorders can often present a significant diagnostic challenge. A systematic approach using all available clinical, laboratory, radiographic, histologic, immunohistochemical and ultrastructural data is essential for proper discrimination between the numerous histiocytoses.

Leptomeningeal dissemination of a pediatric neoplasm with 1p19q deletion showing mixed immunohistochemical features of an oligodendroglioma and neurocytoma.

Leptomeningeal dissemination of an oligodendroglioma is rarely reported in the neurosurgical literature, especially in cases with a classical 1p19q deletion. The authors describe a case wherein a 1p19q deletion in a disseminated tumor with mixed immunohistochemical features of oligodendroglioma and neurocytoma was encountered and treated. Stereotactic right frontal craniotomy was undertaken for obtaining definitive histological diagnosis. The results revealed a neuroectodermal neoplasm with histologic and immunohistochemical features of oligodendroglioma and neurocytoma. FISH analysis confirmed classical 1p19q deletion. The patient was treated postoperatively with chemotherapy and radiation therapy. He showed good clinical response and remains alive 16 months after diagnosis.

External decompressive craniectomy including resection of temporal muscle and fascia in malignant hemispheric infarction.

Decompressive craniectomy procedures are used for malignant hemispheric infarctions. However, the temporal muscle and fascia are significant limiting factors for external herniation of an edematous brain. Therefore, the authors performed a decompressive craniectomy and expansive duraplasty combined with resection of the temporal muscle and fascia for 15 patients with a malignant hemispheric infarction. The volume of the maximum external herniation that was measured on the basis of a CT volumetry study ranged from 130 to 300 ml (mean +/- standard deviation, 200 +/- 64 ml) on postoperative Day 3.2 +/- 1.5 (range 2-5 days postoperatively). The mean value represented a 2-fold volume expansion in comparison with the conventional decompressive craniectomy, and the greater the external herniation obtained by external decompression, the smaller the midline brain shift after surgery. The mortality rate, favorable outcomes (modified Rankin Scale Scores 1-3), and unfavorable outcomes were 20, 60, and 20%, respectively, and the masticatory function was only minimally affected. Furthermore, a cranioplasty involving reconstruction of the temporal muscle defect performed using a MEDPOR implant resulted in good cosmetic outcomes with no temporal hollow. Resection of the temporal muscle in a decompressive craniectomy was shown to provide greater decompression and better clinical outcomes for malignant hemispheric infarctions at an acceptable cost of minimal masticatory dysfunction and cosmetic disfigurement.

Albert Wojciech Adamkiewicz (1850-1921): unsung hero behind the eponymic artery.

The artery of Adamkiewicz is an important radiculomedullary artery supplying the spinal cord, especially the lumbar enlargement. Anatomical knowledge of this artery is important for avoiding serious neurological complications during surgery performed in this region--for neurosurgeons and interventional radiologists treating intramedullary tumors and spinal arteriovenous malformations, traumatologists performing spinal fusions, thoracic surgeons treating aortic aneurysms, and urologists and pediatric surgeons conducting retroperitoneal dissections. However, the biography of the talented Polish pathologist Albert Adamkiewicz, after whom the landmark artery is named, has not been described adequately in the existing neurosurgical literature. The authors bring to light the historical perspective of the eponymic artery and provide a recapitulation of other significant contributions made by Adamkiewicz, mostly involving the nervous system. His research papers on the histology of neuronal tissues and neurodegenerative diseases had high scientific merit, but the discovery of the anticancer antitoxin "cancroin" and his postulation of a cancer-causing parasite he named "Coccidium sarcolytus" met with harsh criticism and eventually led to his ill fame. The biography is supplemented with a brief overview of the important surgical implications of the artery of Adamkiewicz.

The legendary contributions of Thomas Willis (1621-1675): the arterial circle and beyond.

Thomas Willis established neurology as a distinct discipline and made significant original contributions to many related fields including anatomy, pathology, cardiology, endocrinology, and gastroenterology. He is most remembered for his work in elucidating the function and anatomy of the circle of Willis. Willis' accomplishments and research methods can be credited in large part to his unconventional medical education which did not include traditional teachings, but rather emphasized learning through clinical practice. Although Willis was not the first to describe the arterial circle, he was the first to describe its function and provide a complete, undisputed illustration through his own innovative use of dye studies. The Willis classification of cranial nerves was still in use over 100 years after its original description. He has also described several disease entities and named many brain structures. Willis' accomplishments in comparative anatomy and understanding the pathophysiology of various diseases through original multidisciplinary experimental work in a clinical setting reveal that he was a true pioneer in translational research.

Minimally invasive anterior vertebroplasty for C-2 metastatic lesions.

The authors describe a technique for minimally invasive anterior vertebroplasty for treating metastatic disease of the C-2 vertebra and discuss its application in 2 cases. After a 2-cm lateral neck incision is made, blunt dissection is performed toward the anterior inferior endplate of the C-2 vertebra. An 11-gauge needle is introduced through a tubular sheath and tapped into the inferior endplate of C-2, with biplanar fluoroscopy being performed to confirm position. The needle is subsequently advanced across the fracture line and into the odontoid process. Under fluoroscopic guidance, 2 ml of methylmethacrylate is injected into the odontoid process and vertebral body. This method is advantageous as 1) hyperextension of the neck is not performed, 2) the chance of inadvertent neurovascular or submandibular gland injury is minimized, 3) the possibility of cement leakage is decreased, and 4) hemostasis is better achieved under direct vision.

Modern psychosurgery before Egas Moniz: a tribute to Gottlieb Burckhardt.

The history of modern psychosurgery has been written in several ways, weaving around many pioneers in the field during the 19th century. Often neglected in this history is Gottlieb Burckhardt (1836-1907), who performed the first psychosurgical procedures as early as 1888, several decades before the work of Egas Moniz (1874-1955). The unconventional and original case series of Burckhardt, who claimed success in 50% of patients (3 of 6), had met with overt criticism from his contemporary medical colleagues. The authors describe 2 illustrative cases of cortical extirpation performed by Burckhardt and review his pioneering case series for surgical outcome, despite the ambiguity in postoperative evaluation criteria. Although Burckhardt discontinued the project after publication of his surgical results in 1891, neurosurgeons around the world continued to investigate psychosurgery and revitalized his ideas in 1910; psychosurgery subsequently developed into a full-fledged neurosurgical specialty.

Laser-Assisted Excision of Coil Mass While Clipping Recurrent Intracranial Aneurysms After Prior Endovascular Coiling: Our Initial Experience.

BACKGROUND: Excision of coil mass during clipping of recurrent or residual aneurysms after prior endovascular coiling is challenging. We evaluated the use of the carbon dioxide laser for safe and effective removal of coils during aneurysm surgery. Two cases are presented. CASE DESCRIPTION: The first patient was a 56-year-old man with a previously coiled ruptured anterior communicating artery aneurysm. Angiography at 3-year follow-up showed recurrent aneurysm, which could not be coiled again owing to technical reasons. An aneurysm clip could not be safely applied owing to the weight of the coil mass compromising the parent vessel lumen. Laser-assisted coil mass resection was performed before permanent clip application. Intraoperative cerebral angiography showed complete obliteration of the aneurysm. The second patient was a 69-year-old woman with a previously coiled unruptured middle cerebral artery aneurysm. Angiography at 2-year follow-up showed recurrence of the aneurysm, which could not be coiled again owing to technical reasons. Laser-assisted coil mass resection was performed before the aneurysm was safely clipped. Intraoperative angiography showed complete obliteration of the aneurysm. No complications occurred using the carbon dioxide laser. At 1-year follow-up, both patients were asymptomatic with no evidence of aneurysmal recurrence. CONCLUSIONS: Excision of coil mass is required while treating recurrent and/or residual intracranial aneurysms that were previously treated by endovascular technique. The use of carbon dioxide laser assistance while retrieving these coils is safe and effective.

In Situ Left Azygous Anterior Cerebral Artery to Right Pericallosal Artery Bypass for Treatment of a Giant Right A1/2 Aneurysm: 2-Dimensional Operative Video.

Here we present a 46-yr-old man with recurrent syncopal episodes thought to be of cardiac origin. He was eventually found to harbor a giant, partially thrombosed, saccular aneurysm arising from the A1/A2 segment of the right anterior cerebral artery with foramen of Monro obstruction and a trapped left-sided ventricular system. An azygous left A2 artery segment supplied both callosomarginal arteries. We performed an in situ side-to-side anastomosis between the distal left azygous anterior cerebral artery and the right pericallosal artery, which was previously supplied by the right A1. The right A1 was clip ligated, and the aneurysm evacuated with an ultrasonic aspirator. Postoperatively, the patient did well with no recurrence of the aneurysm and resolution of his preoperative obstructive hydrocephalus. He continues to be independent >7 yr post surgery. His 6-mo follow-up angiogram revealed a patent bypass.

Candida parapsilosis Infection of Ventriculoperitoneal Shunt in Adult: Case Report and Literature Review.

BACKGROUND: Candida parapsilosis is an incredibly rare cause of ventriculoperitoneal (VP) shunt infections, with only 1 adult case reported in the literature to date. CASE DESCRIPTION: We describe the case of a 45-year-old man admitted for a traumatic fall and subsequently treated with VP shunt placement for obstructive hydrocephalus secondary to a cerebellar contusion and intraventricular hemorrhage. Eight months following VP shunt placement, the patient presented with a 2-month history of clear fluid leakage through a dehiscent surgical abdominal wound overlying the distal VP shunt. Cerebrospinal fluid cultures were obtained and grew C. parapsilosis. The patient subsequently underwent VP shunt externalization and began antifungal treatment with intravenous liposomal amphotericin B. Cerebrospinal fluid studies continued to redemonstrate C. parapsilosis infection, for which VP shunt removal and external ventricular drain placement was performed. Three days into treatment with amphotericin B, he endured significant nephrotoxicity necessitating a switch to oral fluconazole. Following 3 weeks of oral fluconazole treatment with negative serial cerebrospinal fluid cultures, the patient underwent external ventricular drain removal and VP shunt insertion. Following the procedure and 22 total days of oral fluconazole treatment, our patient recovered well and was discharged to a rehabilitation facility in stable condition. CONCLUSIONS: In our report, we describe the clinical course of our patient and offer a review and analysis of the most up-to-date literature concerning C. parapsilosis shunt infections, as well as treatment guidelines for central nervous system candidiasis.

MicroRNA and brain tumors: a cause and a cure?

Malignant brain tumors, including high-grade gliomas, are among the most lethal of all cancers. Despite considerable advances, including multi-modal treatments with surgery, radiotherapy, and chemotherapy, the overall prognosis remains dismal for patients diagnosed with these tumors. With the discovery of RNA interference (RNAi) for target-specific gene silencing via small interfering RNA (siRNA), a novel method to target malignant gliomas has been exposed, an endeavor that is aggressively being carried out in numerous laboratories. However, practical difficulties in tissue- or organ-specific targeting of therapeutic quantities of siRNA still preclude its applicability in a clinical setting. MicroRNA (miRNA), an endogenously expressed form of siRNA, not only presents an alternate method to induce RNAi in a given diseased tissue or organ, but also exposes a unique set of diagnostic markers that can be used to identify, and then differentiate between tumor grades. Thus, miRNA can be considered the cells' answer to siRNA. Discovered over a decade ago, miRNA is fast becoming recognized as crucial in regulating gene expression in cancers. Therein lies the therapeutic potential of miRNA, as it may now be possible to induce or inhibit RNAi in a given diseased cell population by controlling the cells' miRNA expression profile. This review outlines the potential of miRNA as a therapeutic strategy against high-grade gliomas, and also the technological hurdles that need to be addressed before this promising technique can be administered in a clinical setting.

Intraoperative brain shift prediction using a 3D inhomogeneous patient-specific finite element model.

OBJECT: The aims of this study were to develop a three-dimensional patient-specific finite element (FE) brain model with detailed anatomical structures and appropriate material properties to predict intraoperative brain shift during neurosurgery and to update preoperative magnetic resonance (MR) images using FE modeling for presurgical planning. METHODS: A template-based algorithm was developed to build a 3D patient-specific FE brain model. The template model is a 50th percentile male FE brain model with gray and white matter, ventricles, pia mater, dura mater, falx, tentorium, brainstem, and cerebellum. Gravity-induced brain shift after opening of the dura was simulated based on one clinical case of computer-assisted neurosurgery for model validation. Preoperative MR images were updated using an FE model and displayed as intraoperative MR images easily recognizable by surgeons. To demonstrate the potential of FE modeling in presurgical planning, intraoperative brain shift was predicted for two additional head orientations. Two patient-specific FE models were constructed. The mesh quality of the resulting models was as high as that of the template model. One of the two FE models was selected to validate model-predicted brain shift against data acquired on intraoperative MR imaging. The brain shift predicted using the model was greater than that observed intraoperatively but was considered surgically acceptable. CONCLUSIONS: A set of algorithms for developing 3D patient-specific FE brain models is presented. Gravity-induced brain shift can be predicted using this model and displayed on high-resolution MR images. This strategy can be used not only for updating intraoperative MR imaging, but also for presurgical planning.

Lower airway disease and pituitary surgery: Is there an association with postoperative cerebrospinal fluid leak?

OBJECTIVES/HYPOTHESIS: To explore the relationship between lower airway disease and postoperative cerebrospinal fluid (CSF) rhinorrhea among patients undergoing pituitary surgery STUDY DESIGN: Retrospective review. METHODS: A retrospective review of the Healthcare Cost and Utilization Project's 2013 National Inpatient Sample was conducted to characterize the hospital stay and surgical outcomes of patients undergoing pituitary surgery. Patients with lower airway disease (including chronic obstructive pulmonary disease and asthma) were compared to a disease-free population identifying demographics and complications over-represented in the lower airway group. RESULTS: The majority of hypophysectomies (92.1%) were performed via a transsphenoidal approach. Among transsphenoidal patients, individuals with asthma (92.8% of the lower airway disease cohort) harbored a greater postoperative CSF leak rate (4.7% vs. 2.7%, P = .022), and were more likely to develop postoperative diabetes insipidus (6.2% vs. 4.1%, P = .024) and neurological complications (13.0% vs. 9.6%, P = .010) when compared to a lower airway disease-free cohort. Patients with CSF rhinorrhea had longer lengths of stay (7.8 days vs. 4.5 days, P < .001) and higher discharge costs ($148,309 vs. $76,246, P < .001). A binary logistic regression model identified having asthma (P = .042), being female (P = .011), and having gastroesophageal reflux disease (P = .006) as independent predictors of postoperative CSF rhinorrhea. CONCLUSIONS: Several patient comorbidities including asthma are associated with a greater risk of postoperative CSF rhinorrhea. Perioperative lower airway assessment and disease control may potentially decrease one's risk of this complication, although further inquiry is urgently needed to identify optimal preventive strategies. LEVEL OF EVIDENCE: 2c. Laryngoscope, 127:1543-1550, 2017.

RNAi based approaches to the treatment of malignant glioma.

RNA interference (RNAi) is a recently discovered, powerful molecular mechanism that can be harnessed to engineer gene-specific silencing in mammalian tissues. A mechanism, where short double-stranded RNA (dsRNA) molecules, when introduced into cells elicit specific "knock-down" of gene expression via degradation of targeted messenger RNA, has lately become the technique of choice for analysis of gene function in oncology research. Thus, RNAi is currently being extensively evaluated as a potential therapeutic strategy against malignant gliomas, since surgical, radiological, and chemotherapeutic interventions during the past few decades have done little to improve the poor prognosis rate for patients with these dreaded tumors. This review summarizes the pre-clinical studies that are currently underway to test the validity of RNAi as a potential therapeutic strategy against malignant gliomas, and discusses the potential technical hurdles that remain to be overcome before the technique can become a promising clinical therapy to combat this frequently lethal disease.