Background: The use of stent-assisted coiling (SAC) has been shown to be a treatment option for complex aneurysms. We reviewed systematically the immediate and mid-term angiographic results following treatment of wide-necked aneurysms with self-expanding stents and coils, as well as the peri- and postprocedural rate of complications. Methods: A computerized database search was conducted from 01/2000 to 04/2011 using appropriate indexed terms on Pubmed. Inclusion criteria were: (1) homogeneous populations of ≥10 patients with wide-necked aneurysms; (2) use of a self-expandable neurovascular stent and coils for aneurysm treatment; (3) immediate and follow-up angiographic results; and (4) periprocedural and delayed thrombotic complications. Results: Seventeen studies were included, containing retrospectively collected data on 656 patients/702 aneurysms. The target aneurysm was located on the anterior circulation in 78.4% of patients. The immediate rate of complete occlusion was 46.3%, (19.3-98.1%). The intra- and postprocedural rate of intrastent thrombosis or thromboembolic event was 4.6% and 4.3%, respectively. Complete occlusion was documented in 71.9% at last angiographic follow-up. The rate of recanalization was 13.2% of aneurysms (0-28.8%). Delayed in-stent stenosis occurred in 5.3% cases (0-20.6%). Conclusion: SAC has been considered a treatment option for selected wide-necked aneurysms in some institutions. The use of intracranial stents should take into consideration the risk of ischemic complications, recanalization, delayed in-stent stenosis; and the currently unknown lifetime risks for stenosis, vascular injury, device failure, and aneurysm recurrence related to intracranial stenting. There is an evident need for a prospective multicenter registry for all treated patients with SAC.

Background: This is an analysis of papers published by Iranian neurosurgeons while working in Iran until the year 2010. Methods: We collected bibliometric data and assigned a level of evidence (LOE) for each paper and compared neurosurgical research productivity across three time periods (before 1990, between 1991 and 2000, and after 2000). For further illustration, the annual growth rates of Iranian publications were calculated for all papers published after 1995. Results: We found a total of 1196 papers by 422 Iranian neurosurgeons. Five authors accounted for 22.9% of the papers. The average number of authors for each published manuscript was 3.48 and increased significantly from 2.0 to 4.0 across the three investigated periods ( P < 0.001). 58.9% of Iranian papers were published in local journals only. A total of 74.6% articles were published after 2000, which was a significant increase compared with the decades before ( P < 0.001). Original articles and case reports accounted for 63.8% and 31.1% of the publications, respectively. The proportion of case reports decreased while the proportion of original articles increased across the three time periods ( P < 0.001). The adjusted growth rate for the total number of publications, original articles, case reports, clinical trials, and randomized clinical trials (RCTs) were 14.4%, 16.6%, 10.7%, 13.46%, and 14.7% per year, respectively. Overall, the four most frequently investigated topics were spine (27.3%), trauma (22.3%), tumor (19.1%), and vascular diseases (13.5%). The mean impact factor for journals publishing these studies and average number of citations for each paper (obtained from web of science) were found to be 1.2 and 5.46, respectively. A partitioning of these publications into assigned categories reflecting the LOE of each paper yielded the following LOE distribution for all assessed publications: Ib: 6.02%, Ic: 0.3%, IIa: 0.2%, IIb: 5.4%, IIc: 0.41%, IIIb: 4.8%, IV: 22.5%, and V: 1.2%. The relative number of publications categorized into higher LOE classes increased over the three investigated periods ( P = 0.003). Based on growth curve model, the rate of increase in total numbers of publications following each position change from nonuniversity affiliated neurosurgeon to university affiliated and from university affiliated neurosurgeon to chairman university affiliated neurosurgeon was 81%. Conclusions: A considerable increase in amount and quality of Iranian papers was observed during the past decade as reflected in a higher number of papers categorized in upper LOE classes.

Background: During the past several decades, numerous centers have acquired significant expertise in the treatment of skull base pathologies. Favorable outcomes are not only due to meticulous surgical planning and execution, but they are also related to the collaborative efforts of multiple disciplines. We review the impact of teamwork on patient care, elaborate on the key processes for successful teamwork, and discuss its challenges. Methods: Pubmed and Medline databases were searched for publications from 1970 to 2012 using the following keywords: "teamwork", "multidisciplinary", "interdisciplinary", "surgery", "skull base", "neurosurgery", "tumor", and "outcome". Results: Current literature testifies to the complexity of establishing and maintaining teamwork. To date, few reports on the impact of teamwork in the management of skull base pathologies have been published. This lack of literature is somewhat surprising given that most patients with skull base pathology receive care from multiple specialists. Common factors for success include a cohesive and well-integrated team structure with well-defined procedural organization. Although a multidisciplinary work force has clear advantages for improving today's quality of care and propelling research efforts for tomorrow's cure, teamwork is not intuitive and requires training, guidance, and executive support. Conclusions: Teamwork is recommended to improve quality over the full cycle of care and consequently patient outcomes. Increased recognition of the value of an integrated team approach for skull base pathologies will hopefully encourage centers, physicians, allied health caregivers, and scientists devoted to treating these patients and advancing the field of knowledge to invest the time, effort, and resources to optimize and organize their collective expertise.

There is increasing evidence of an interaction between inflammatory cytokines and glutamate receptors among a number of neurological diseases including traumatic brain injuries, neurodegenerative diseases and central nervous system (CNS) infections. A number of recent studies have now suggested a strong relation between inflammatory mechanisms and excitatory cascades and these may play a role in glioma invasiveness and proliferation. Chronic inflammation appears to be a major initiating mechanism in most human cancers, involving cell-signaling pathways, which are responsible for cell cycling, cancer cell migration, invasion, tumor aggressiveness, and angiogenesis. It is less well appreciated that glutamate receptors also play a significant role in both proliferation and especially glioma invasion. There is some evidence that sustained elevations in glutamate may play a role in initiating certain cancers and new studies demonstrate an interaction between inflammation and glutamate receptors that may enhance tumor invasion and metastasis by affecting a number of cell-signaling mechanisms. These mechanisms are discussed in this paper as well as novel treatment options for reducing immune-glutamate promotion of cancer growth and invasion.

Our knowledge concerning the workings of the immune system has evolved considerably over the past 20 years, with great strides being made as regard to complex interactions and repertoire of effector reactions under a host of conditions. Many of our previous understandings have been challenged, especially concerning tumor immunology and autoimmunity. Also of critical importance is our understanding of how the immune system terminates its attacks and the mechanisms used to regulate the balance between proinflammatory and antiinflammatory mechanisms, so as to prevent excessive immune bystander damage. I will discuss in part I the basic physiology of innate immune function and the immune systems reactions to invasion by microorganisms.

Background: Although persistent trigeminal artery (PTA) is uncommonly identified, knowledge of this structure is essential for clinicians who interpret cranial imaging, perform invasive studies of the cerebral vasculature, and operate this region. Methods: A review of the medical literature using standard search engines was performed to locate articles regarding the PTA, with special attention with anatomical descriptions. Results: Although anatomical reports of PTA anatomy are very scarce, those were analyzed to describe in detail the current knowledge about its anatomical relationships and variants. Additionally, the embryology, classification, clinical implications, and imaging modalities of this vessel are extensively discussed. Conclusions: Through a comprehensive review of isolated reports of the PTA, the clinician can better understand and treat patients with such an anatomical derailment.

Background: We sought to review the current literature with regards to future risks of hemorrhage following cerebral revascularization in Moyamoya disease (MMD). Methods: We performed a comprehensive literature review using PubMed to inspect the available data on the risk of hemorrhage after revascularization in MMD. Results: In this review, we identify the risk factors associated with hemorrhage in MMD both before and after cerebral revascularization. We included proposed pathophysiology of the hemorrhagic risk, role of the type of bypass performed, treatment options, and future needs for investigation. Conclusions: The published cases and series of MMD treatment do show a risk of hemorrhage after treatment with either direct or indirect bypass both in the immediate as well as long-term future. While there are no discernible patterns in the rate of these hemorrhages, there is Class III evidence for the predictive effect of multiple microbleeds on preoperative imaging. Also, whereas revascularization, both direct and indirect, has been shown to reduce ischemic complications from MMD, there is not an association with the risk of hemorrhage after the procedure. Further studies need to be performed to help evaluate what the risk factors are and how to counsel patients as to the long-term outlook of this disease process.

Our understanding of the pathophysiological and biochemical basis of a number of neurological disorders has increased enormously over the last three decades. Parallel with this growth of knowledge has been a clearer understanding of the mechanism by which a number of naturally occurring plant extracts, as well as whole plants, can affect these mechanisms so as to offer protection against injury and promote healing of neurological tissues. Curcumin, quercetin, green tea catechins, balcalein, and luteolin have been extensively studied, and they demonstrate important effects on cell signaling that go far beyond their antioxidant effects. Of particular interest is the effect of these compounds on immunoexcitotoxicity, which, the authors suggest, is a common mechanism in a number of neurological disorders. By suppressing or affecting microglial activation states as well as the excitotoxic cascade and inflammatory mediators, these compounds dramatically affect the pathophysiology of central nervous system disorders and promote the release and generation of neurotrophic factors essential for central nervous system healing. We discuss the various aspects of these processes and suggest future directions for study.

Background: There has been a tremendous amount of interest focused on the topic of concussions over the past few decades. Neurosurgeons are frequently consulted to manage patients with mild traumatic brain injuries (mTBI) that have radiographic evidence of cerebral injury. These injuries share significant overlap with concussions, injuries that typically do not reveal radiographic evidence of structural injury, in the realms of epidemiology, pathophysiology, outcomes, and management. Further, neurosurgeons often manage patients with extracranial injuries that have concomitant concussions. In these cases, neurosurgeons are often the only "concussion experts" that patients encounter. Results: The literature has been reviewed and data have been synthesized on the topic including sections on historical background, epidemiology, pathophysiology, diagnostic advances, clinical sequelae, and treatment suggestions, with neurosurgeons as the intended target audience. Conclusions: Neurosurgeons should have a fundamental knowledge of the scientific evidence that has developed regarding concussions and be prepared to guide patients with treatment plans.

Background: Interspinous fusion devices (IFDs) are increasingly offered to patients over the age of 50 with lumbar spinal stenosis and intermittent neurogenic claudication. Here, we review the literature on complication rates, reoperation rates, and outcomes for implanting IFD, and offer an assessment of IFD charges at a single institution in 2010. Methods: The literature concerning IFD implants was reviewed with particular attention focused on complications, reoperation rates, and outcomes. Additionally, the costs of implanting 31 IFD devices in 16 patients at one to three levels at a single institution in 2010 are presented. Results: Reviewing the spinal literature concerning the postoperative status of IFD followed over an average of 23-42.9 postoperative months revealed that IFD resulted in 11.6-38% complication rate, 4.6-85% reoperation rate, and 66.7-77% frequency of poor outcomes. Additionally, the 31 devices implanted in 16 patients at a single university hospital in 2010 cost a total of $576,407. Conclusions: With high maximal complication rates (38%), reoperation rates (85%), poor outcomes (77%), and high costs ($576,407 for 31 devices in 16 patients), the utilization and implantation of IFD remains extremely controversial and should be investigated further.

In the fall of 1999, the Institute of Medicine released "To Err is Human: Building a Safer Health System," a sobering report on the safety of the American healthcare industry. This work and others like it have ushered in an era where the science of quality assurance has quickly become an integral facet of the practice of medicine. One critical component of this new era is the development, application, and refinement of checklists. In a few short years, the checklist has evolved from being perceived as an assault on the practitioners' integrity to being welcomed as an important tool in reducing complications and preventing medical errors. In an effort to further expand the neurosurgical community's acceptance of surgical checklists, we review the rationale behind checklists, discuss the history of medical and surgical checklists, and remark upon the future of checklists within our field.

Background: Although the frequency of spinal surgical procedures has been increasing, particularly in patients of age 65 and over (geriatric), multiple overlapping comorbidities increase their risk/complication rates. Nevertheless, sometimes these high-risk geriatric patients are considered for "unnecessary", too much (instrumented fusions), or too little [minimally invasive surgery (MIS)] spine surgery. Methods: In a review of the literature and reanalysis of data from prior studies, attention was focused on the increasing number of operations offered to geriatric patients, their increased comorbidities, and the offers for "unnecessary" spine fusions, including both major open and MIS procedures. Results: In the literature, the frequency of spine operations, particularly instrumented fusions, has markedly increased in patients of age 65 and older. Specifically, in a 2010 report, a 28-fold increase in anterior discectomy and fusion was observed for geriatric patients. Geriatric patients with more comorbid factors, including diabetes, hypertension, coronary artery disease (prior procedures), depression, and obesity, experience higher postoperative complication rates and costs. Sometimes "unnecessary," too much (instrumented fusions), and too little (MIS spine) surgeries were offered to geriatric patients, which increased the morbidity. One study observed a 10% complication rate for decompression alone (average age 76.4), a 40% complication rate for decompression/limited fusion (average age 70.4), and a 56% complication rate for full curve fusions (average age 62.5). Conclusions: Increasingly, spine operations in geriatric patients with multiple comorbidities are sometimes "unnecessary," offer too much surgery (instrumentation), or too little surgery (MIS).

Background: Neurosurgical intervention involving the scalp may cause neuralgia or other pain syndromes. Therefore, a comprehensive understanding of scalp innervation may be helpful in prevention of pain potentially induced by surgery. Methods: Using standard search engines, a review of the literature regarding the anatomy of the nerves that innervate the scalp was performed with attention given to anatomic landmarks. Results: This paper provides a comprehensive review of the anatomy, embryology, pathology, and neurosurgical application of the knowledge of the innervation of the scalp. Conclusions: Knowledge of the nerves that supply the scalp is important to the neurosurgeon who hopes to maximize patient recovery and minimize post-procedural complications.

Background: High-grade primary and metastatic central nervous system (CNS) tumors are common, deadly, and refractory to conventional therapy and continue to be therapeutically challenging. A key nodal transcriptional factor, the signal transducer and activator of transcription 3 (STAT3), drives the fundamental components of tumor malignancy and metastases in the CNS by enhancing proliferation, angiogenesis, invasion, metastasis, and immunosuppression. The introduction of STAT3 inhibitors in clinical trials for this patient population is imminent. Methods: STAT3 inhibitors have been extensively tested in a variety of preclinical murine models. Results: The STAT3 inhibitor, WP1066, has displayed marked efficacy with minimal toxicity against malignancy in murine models, including established intracerebral tumors. The mechanism of this in vivo efficacy of the STAT3 blockade agents is a combination of direct tumor cytotoxicity and immune cytotoxic clearance. Conclusions: Given their direct antitumor cytotoxic effects, STAT3 inhibitors may exert therapeutic activity in the monotherapy setting but may also have compelling use as immunotherapeutic modulators or as a salvage therapy.

Background: Tinnitus, a profoundly widespread auditory disorder, is characterized by the perception of sound in the absence of external stimulation. The aim of this work is to review the various surgical treatment options for tinnitus, targeting the various disruption sites along the auditory pathway, as well as to indicate novel neuromodulatory techniques as a mode of tinnitus control. Methods: A comprehensive analysis was conducted on published clinical and basic neuroscience research examining the pathophysiology and treatment options of tinnitus. Results: Stereotactic radiosurgery methods and microvascular decompressions are indicated for tinnitus caused by underlying pathologies such as vestibular schwannomas or neurovascular conflicts of the vestibulocochlear nerve at the level of the brainstem. However, subsequent hearing loss and secondary tinnitus may occur. In patients with subjective tinnitus and concomitant sensorineural hearing loss, cochlear implantation is indicated. Surgical ablation of the cochlea, vestibulocochlear nerve, or dorsal cochlear nucleus, though previously suggested in earlier literature as viable treatment options for tinnitus, has been shown to be ineffective and contraindicated. Recently, emerging research has shown the neuromodulatory capacity of the somatosensory system at the level of the trigeminal nerve on the auditory pathway through its inputs at various nuclei in the central auditory pathway. Conclusion: Tinnitus remains to be a difficult disorder to treat despite the many surgical interventions aimed at eliminating the aberrant neuronal activity in the auditory system. A promising novel neuromodulatory approach using the trigeminal system to control such a bothersome and difficult-to-treat disorder deserves further investigation and controlled clinical trials.

Background: While numerous laboratory studies have searched for neuroprotective treatment approaches to traumatic brain injury, no therapies have successfully translated from the bench to the bedside. Concussion is a unique form of brain injury, in that the current mainstay of treatment focuses on both physical and cognitive rest. Treatments for concussion are lacking. The concept of neuro-prophylactic compounds or supplements is also an intriguing one, especially as we are learning more about the relationship of numerous sub-concussive blows and/or repetitive concussive impacts and the development of chronic neurodegenerative disease. The use of dietary supplements and herbal remedies has become more common place. Methods: A literature search was conducted with the objective of identifying and reviewing the pre-clinical and clinical studies investigating the neuroprotective properties of a few of the more widely known compounds and supplements. Results: There are an abundance of pre-clinical studies demonstrating the neuroprotective properties of a variety of these compounds and we review some of those here. While there are an increasing number of well-designed studies investigating the therapeutic potential of these nutraceutical preparations, the clinical evidence is still fairly thin. Conclusion: There are encouraging results from laboratory studies demonstrating the multi-mechanistic neuroprotective properties of many naturally occurring compounds. Similarly, there are some intriguing clinical observational studies that potentially suggest both acute and chronic neuroprotective effects. Thus, there is a need for future trials exploring the potential therapeutic benefits of these compounds in the treatment of traumatic brain injury, particularly concussion.

Background : Post-transplantation primary central nervous system lymphoma (PT-PCNSL) is a rare neoplasm that can develop within months to years after transplantation, and imaging often reveals multiple lesions with homogeneous or ring enhancement. The clinical and imaging presentation of PT-PCNSL can often be nonspecific and present a diagnostic challenge. Case Description : A 56-year-old woman presented to a tertiary university emergency room with altered mental status 15 months after undergoing renal transplantation. On brain MRI, she was found to have three rim-enhancing mass lesions, and biopsy revealed PT-PCNSL. Conclusion : There has been a steady increase in the number of patients living following organ transplantation in the United States and an increasing likelihood that PT-PCNSL will increasingly be encountered in neurosurgical practice. We present here a case of PT-PCNSL and a brief review of the relevant clinical characteristics, treatment options, and prognosis of PT-PCNSL.

Background: Glial scar (GS) is the most important inhibitor factor to neuroregeneration after spinal cord injury (SCI) and behaves as a tertiary lesion. The present review of the literature searched for representative studies concerning GS and therapeutic strategies to neuroregeneration. Methods: The author used the PubMed database and Google scholar to search articles published in the last 20 years. Key words used were SCI, spinal cord (SC) inflammation, GS, and SCI treatment. Results: Both inflammation and GS are considered important events after SCI. Despite the fact that firstly they seem to cause benefit, in the end they cause more harm than good to neuroregeneration. Each stage has its own aspects under the influence of the immune system causing inflammation, from the primary to secondary lesion and from those to GS (tertiary lesion). Conclusion: Future studies should stress the key points where and when GS presents itself as an inhibitory factor to neuroregeneration. Considering GS as an important event after SCI, the author defends GS as being a tertiary lesion. Current strategies are presented with emphasis on stem cells and drug therapy. A better understanding will permit the development of a therapeutic basis in the treatment of the SCI patients considering each stage of the lesion, with emphasis on GS and neuroregeneration.

Some individuals suffering from mild traumatic brain injuries, especially repetitive mild concussions, are thought to develop a slowly progressive encephalopathy characterized by a number of the neuropathological elements shared with various neurodegenerative diseases. A central pathological mechanism explaining the development of progressive neurodegeneration in this subset of individuals has not been elucidated. Yet, a large number of studies indicate that a process called immunoexcitotoxicity may be playing a central role in many neurodegenerative diseases including chronic traumatic encephalopathy (CTE). The term immunoexcitotoxicity was first coined by the lead author to explain the evolving pathological and neurodevelopmental changes in autism and the Gulf War Syndrome, but it can be applied to a number of neurodegenerative disorders. The interaction between immune receptors within the central nervous system (CNS) and excitatory glutamate receptors trigger a series of events, such as extensive reactive oxygen species/reactive nitrogen species generation, accumulation of lipid peroxidation products, and prostaglandin activation, which then leads to dendritic retraction, synaptic injury, damage to microtubules, and mitochondrial suppression. In this paper, we discuss the mechanism of immunoexcitotoxicity and its link to each of the pathophysiological and neurochemical events previously described with CTE, with special emphasis on the observed accumulation of hyperphosphorylated tau.

Neurosurgery has always had a strong interest in innovating new technologies to improve neurological function and quality of life. Now, novel interventions that modulate central nervous system activity at the nanoparticle, molecular, genetic, cellular, and network level all seem to be on the horizon. Advances in biomedical engineering, including imaging techniques, sensor technologies, bio-signal analyses and classification, and prosthetics, have particularly accelerated the development brain-computer interfaces (BCI). Clinical translation of BCI technology will require multidisciplinary collaboration and effort to develop all necessary components, including advanced sensor technologies, sophisticated and real-time signal analyses and classifications, and complex effector technologies. Although the field has primarily been driven by basic scientists, neurosurgeons need to play a critical role in the further development of each component of these technologies because of our unique access to the awake and behaving human brain, our perspective with respect to the practicalities of technology implementation in the clinical setting, and because of our historical commitment to improving neurological function and quality-of-life. The current state of BCI research, the challenges, and the critical role that neurosurgeons must play in BCI development are briefly reviewed to advocate for increased neurosurgical involvement and commitment to this emerging translational field.

Background : Over years, surgical training is changing and years of tradition are being challenged by legal and ethical concerns for patient safety, work hour restrictions, and the cost of operating room time. Surgical simulation and skill training offer an opportunity to teach and practice advanced techniques before attempting them on patients. Simulation training can be as straightforward as using real instruments and video equipment to manipulate simulated "tissue" in a box trainer. More advanced virtual reality (VR) simulators are now available and ready for widespread use. Early systems have demonstrated their effectiveness and discriminative ability. Newer systems enable the development of comprehensive curricula and full procedural simulations. Methods : A PubMed review of the literature was performed for the MESH words "Virtual reality", "Augmented Reality", "Simulation", "Training," and "Neurosurgery". Relevant articles were retrieved and reviewed. A review of the literature was performed for the history, current status of VR simulation in neurosurgery. Results : Surgical organizations are calling for methods to ensure the maintenance of skills, advance surgical training, and credential surgeons as technically competent. The number of published literature discussing the application of VR simulation in neurosurgery training has evolved over the last decade from data visualization, including stereoscopic evaluation to more complex augmented reality models. With the revolution of computational analysis abilities, fully immersive VR models are currently available in neurosurgery training. Ventriculostomy catheters insertion, endoscopic and endovascular simulations are used in neurosurgical residency training centers across the world. Recent studies have shown the coloration of proficiency with those simulators and levels of experience in the real world. Conclusion : Fully immersive technology is starting to be applied to the practice of neurosurgery. In the near future, detailed VR neurosurgical modules will evolve to be an essential part of the curriculum of the training of neurosurgeons.

Background : The rate of postoperative spinal infections varies from 0.4% to 3.5%. Although the introduction of additional preoperative, intraoperative, and postoperative methods of prophylaxis should further reduce spinal infection rates, these measures will not succeed unless surgeons are well informed of their availability, utility, and efficacy. This study provides a review of several preoperative, intraoperative, and postoperative methods of prophylaxis that could minimize the risk of postoperative spinal infections. Various preoperative, intraoperative, and postoperative measures could further reduce the risk of spinal infections. Preoperative prophylaxis against methicillin-resistant Staphylococcus aureus could utilize (1) nasal cultures and Bactroban ointment (mupirocin), and (2) multiple prophylactic preoperative applications of chlorhexidine gluconate (CHG) 4% to the skin. Intraoperative prophylactic measures should not only include the routine use of an antibiotic administered within 60 min of the incision, but should also include copious intraoperative irrigation [normal saline (NS) and/or NS with an antibiotic]. Intraoperatively, instrumentation coated with antibiotics, and/or the topical application of antibiotics may further reduce the infection risk. Whether postoperative infections are reduced with the continued use of antibiotic prophylaxis remains controversial. Other postoperative measures may include utilization of a silver (AgNO ₃ )-impregnated dressing (Silverlon dressing) and the continued use of bed baths with CHG 4%. The introduction of multiple preoperative, intraoperative, and postoperative modalities in addition to standardized prophylaxis may further contribute to reducing postoperative spinal infections.

Background: INFUSE (recombinant human bone morphogenetic protein-2 [rh-BMP-2]; Medtronic, Memphis, TN, USA) is approved by the Federal Drug Administration (FDA) only for use with the lumbar tapered fusion device (LT Cage; Medtronic) to perform single-level anterior lumbar interbody fusions (ALIF: L2-S1 levels). INFUSE, however, is widely utilized in an "off-label" capacity for anterior and/or posterior cervical, thoracic, and lumbar surgery. Nevertheless, Medicare and other insurance companies, are now increasingly denying reimbursement (average cost of a "large" INFUSE to the hospital without overhead $5000-6000) to hospitals for INFUSE when utilized "off-label." Methods: This commentary looks at several representative studies citing the cons associated with utilizing INFUSE in spinal surgery, contraindications, complications, and cost factors. Results: There are multiple cons of utilizing INFUSE in an "off-label" capacity for spinal surgery. Direct contraindications include pregnancy, allergy to titanium, allergy to bovine type I collagen or rhBMP-2, infection, tumor, liver or kidney disease, immunosuppression (e.g., lupus, HIV/AIDS); contraindications are also seen in those receiving radiation, chemotherapy, or steroids. Reported complications include exuberant/ectopic bone formation, paralysis (cord, nerve damage), dural tears, bowel-bladder and sexual dysfunction, respiratory failure, inflammation of adjacent tissues, fetal developmental complications, scar, excessive bleeding, and even death. Complications are so prevalent in the anterior cervical spine, that many surgeons no longer use it in this region. Similarly, INFUSE complications and indications for posterior lumbar interbody fusions (PLIFs) and transforaminal interbody lumbar fusions (TLIFs) should also be reexamined. Conclusions: More surgeons need to question the safety, efficacy, and appropriate "off-label" use of INFUSE in all spine surgeries.

Background : Nearly 11,000 cases of spinal cord injury (SCI) are reported in the United States annually. Current management options give a median survival time of 38 years; however, no rehabilitative measures are available. Stem cells have been under constant research given their ability to differentiate into neural cell lines replacing non functional tissue. Efforts have been made to establish new synapses and provide a conducive environment, by grafting cells from autologous and fetal sources; including embryonic or adult stem cells, Schwann cells, genetically modified fibroblasts, bone stromal cells, and olfactory ensheathing cells and combinations / variants thereof. Methods : In order to discuss the underlying mechanism of SCI along with the previously mentioned sources of stem cells in context to SCI, a simple review of literature was conducted. An extensive literature search was conducted using the PubMed data base and online search engines and articles published in the last 15 years were considered along with some historical articles where a background was required. Results : Stem cell transplantation for SCI is at the forefront with animal and in vitro studies providing a solid platform to enable well-designed human studies. Olfactory ensheathing cells seem to be the most promising; whilst bone marrow stromal cells appear as strong candidates for an adjunctive role. Conclusion : The key strategy in developing the therapeutic basis of stem cell transplantation for spinal cord regeneration is to weed out the pseudo-science and opportunism. All the trials should be based on stringent scientific criteria and effort to bypass that should be strongly discouraged at the international level.

Background: Technical advancements have significantly improved surgical and endovascular treatment of cerebral aneurysms. In this paper, we review the literature with regard to treatment of one of the most common intra-cranial aneurysms encountered by neurosurgeons and interventional radiologists. Conclusions: Anterior clinoidectomy, temporary clipping, adenosine-induced cardiac arrest, and intraoperative angiography are useful adjuncts during surgical clipping of these aneurysms. Coil embolization is also an effective treatment alternative particularly in the elderly population. However, coiled posterior communicating artery aneurysms have a particularly high risk of recurrence and must be followed closely. Posterior communicating artery aneurysms with an elongated fundus, true posterior communicating artery aneurysms, and aneurysms associated with a fetal posterior communicating artery may have better outcome with surgical clipping in terms of completeness of occlusion and preservation of the posterior communicating artery. However, as endovascular technology improves, endovascular treatment of posterior communicating artery aneurysms may become equivalent or preferable in the near future. One in five patients with a posterior communicating artery aneurysm present with occulomotor nerve palsy with or without subarachnoid hemorrhage. Factors associated with a higher likelihood of recovery include time to treatment, partial third nerve deficit, and presence of subarachnoid hemorrhage. Both surgical and endovascular therapy offer a reasonable chance of recovery. Based on level 2 evidence, clipping appears to offer a higher chance of occulomotor nerve palsy recovery; however, coiling will remain as an option particularly in elderly patients or patients with significant comorbidity.

The use of both over-the-counter and prescription nonsteroidal medications is frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medications for chronic and degenerative pain conditions. This article is a literature review of the biochemical pathways of inflammatory pain, the potentially serious side effects of nonsteroidal drugs and commonly used and clinically studied natural alternative anti-inflammatory supplements. Although nonsteroidal medications can be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatment for pain relief, especially for long-term use.

Object: To provide a review of current, high-impact scientific findings pertaining to the biology of cerebral cavernous malformations (CCMs). Methods: A comprehensive literature review was conducted using PubMed to examine the current literature regarding the molecular biology and pathophysiology of CCMs. Results: In this literature review, a comprehensive approach is taken to review the current scientific status of CCMs. This includes discussion of molecular biology and animal models, ultrastructure and angioarchitectural features and immunological methods and hypotheses. Conclusions: Studies examining the molecular biology of CCMs have shown that genes involved in angiogenesis, blood-brain barrier formation, cell size regulation, vascular permeability and apoptosis play critical roles in the ontogeny of this disease. In vivo work suggests the likelihood of a "two-hit mechanism" resulting in somatic mosaicism and biallelic loss of angiogenic genes. The etiological effects of angioarchitecture and immune response within these lesions further complicate the pathophysiology. Future treatment endeavors will necessitate exploitation of the multiple facets of CCM formation to maximize success at CCM prevention or obliteration.