Justin F. Fraser

Endoscopic cranial base surgery: classification of operative approaches.

OBJECTIVE Endoscopic cranial base surgery is a minimal access, maximally aggressive alternative to traditional transfacial, transcranial, or combined open cranial base approaches. Previous descriptions of endoscopic approaches have used varying terminology, which can be confusing to the new practitioner. Indications for surgery are not well defined. Our objective was to create a comprehensive classification system of the various approaches and describe their indications with case examples. METHODS We prospectively compiled a comprehensive database of our endonasal endoscopic operations, detailing the nasal sinus transgressed, the cranial base approach, and the intracranial target for the first 150 consecutive cases performed at our institution. All cases were performed collaboratively by a neurosurgeon and an otolaryngologist. RESULTS We categorized the endonasal endoscopic cranial base operations into four nasal corridors, nine cranial base approaches, and 13 intracranial targets. Each of the various approaches is described in detail and illustrated with case examples. Pathology encountered included pituitary tumor (50%), meningocele/encephalocele (14%), craniopharyngioma and Rathke cleft cyst (10%), meningioma (8%), chordoma (5%), esthesioneuroblastoma (2%), and other (11%). CONCLUSION Endonasal endoscopic cranial base surgery is a minimal access, maximally invasive alternative to open transcranial cranial base approaches for specific indications. A clear understanding of the possible approaches is facilitated by an awareness of the nasal corridors and intracranial targets.

Three-dimensional endoscopic pituitary surgery.

OBJECTIVE We describe a novel 3-dimensional (3-D) stereoendoscope and discuss our early experience using it to provide improved depth perception during transsphenoidal pituitary surgery. METHODS Thirteen patients underwent endonasal endoscopic transsphenoidal surgery. A 6.5-, 4.9-, or 4.0-mm, 0- and 30-degree rigid 3-D stereoendoscope (Visionsense, Ltd., Petach Tikva, Israel) was used in all cases. The endoscope is based on “compound eye” technology, incorporating a microarray of lenses. Patients were followed prospectively and compared with a matched group of patients who underwent endoscopic surgery with a 2-dimensional (2-D) endoscope. Surgeon comfort and/or complaints regarding the endoscope were recorded. RESULTS The 3-D endoscope was used as the sole method of visualization to remove 10 pituitary adenomas, 1 cystic xanthogranuloma, 1 metastasis, and 1 cavernous sinus hemangioma. Improved depth perception without eye strain or headache was noted by the surgeons. There were no intraoperative complications. All patients without cavernous sinus extension (7of 9 patients) had gross tumor removal. There were no significant differences in operative time, length of stay, or extent of resection compared with cases in which a 2-D endoscope was used. Subjective depth perception was improved compared with standard 2-D scopes. CONCLUSION In this first reported series of purely 3-D endoscopic transsphenoidal pituitary surgery, we demonstrate subjectively improved depth perception and excellent outcomes with no increase in operative time. Three-dimensional endoscopes may become the standard tool for minimal access neurosurgery.

Endoscopic endonasal transclival resection of chordomas: operative technique, clinical outcome, and review of the literature

OBJECT Transcranial approaches to clival chordomas provide a circuitous route to the site of origin of the tumor often involving extensive bone drilling and brain retraction, which places critical neurovascular structures between the surgeon and pathology. For certain chordomas, the endonasal endoscopic transclival approach is a novel minimal access, but it is an equally aggressive alternative providing the most direct route to the tumor epicenter. METHODS The authors present a consecutive series of patients undergoing endonasal endoscopic resection of clival chordomas. Extent of resection was determined by postoperative volumetric MR imaging and divided into > 95% and < 95%. RESULTS Seven patients underwent 10 operations. Preoperative cranial neuropathies were present in 4. The mean patient age was 52.0 years. The mean tumor volume was 34.9 cm3. Intraoperative lumbar drainage was used in 1 patient, and the tumors extended intradurally in 3. One patient underwent 2 intentionally palliative procedures for subtotal debulking. Greater than 95% resection was achieved in 7 of 8 operations in which radical resection was the goal (87%). All tumors with volumes < 50 cm3 had > 95% resection (p = 0.05). The overall mean follow-up was 18.0 months. Cranial neuropathies resolved in all 3 patients with cranial nerve VI palsies. One patient with recurrent nasopharyngeal chordoma died of disease progression; another experienced 2 recurrences before receiving radiation therapy. All surviving patients remain progression free. There were no intraoperative complications; however, 1 patient developed a pulmonary embolus postoperatively. There were no postoperative CSF leaks. CONCLUSIONS The endonasal endoscopic transclival approach represents a less invasive and more direct approach than a transcranial approach to treat certain moderate-sized midline skull base chordomas. Longer follow-up is necessary to determine comparability to transcranial approaches for long-term control. Large tumors with significant extension lateral to the carotid artery may not be suitable for this approach.

Minimal access versus open transforaminal lumbar interbody fusion: meta-analysis of fusion rates.

Study Design. A quantitative meta-analysis was conducted on published studies reporting fusion rates after open or minimally invasive/mini-open transforaminal lumbar interbody fusion (TLIF) procedures for single or multilevel degenerative disease including stenosis with spondylolisthesis and degenerative disc disease. Objectives. The primary aim of this study was to establish benchmark fusion rates for open TLIF and minimally invasive TLIF (mTLIF) based on published studies. A secondary goal was to review complication rates for both approaches. Summary of Background Data. Lumbar fusion for the treatment of degenerative disease has evolved from a purely posterior noninstrumented approach to a combination of anterior and/or posterior surgery with instrumentation. The increasingly popular transforaminal approach has advanced to incorporate minimally invasive spinal techniques. There currently exist no controlled comparisons between open TLIF and mTLIF. Methods. A Medline search was performed to identify studies reporting fusion rate on open TLIF or mTLIF with instrumentation. A database including patient demographic information, fusion rate, and complication rate was created. Fusion and complication rates were pooled according to whether TLIF was performed with open or minimally invasive technique. Publication bias was assessed with Eggers test, and adjustments were performed using Duval and Tweedies Trim and Fill algorithm. Results. Twenty-three articles were identified that fit inclusion criteria. In each of the 23 studies, TLIF was performed with pedicle fixation and fusion was evaluated using radiograph or computed tomography scan at minimum 6-month follow-up. Overall, the studies included 1028 patients, 46.8% of which were female. The mean age of all patients was 49.7 (range, 38–64.9), and mean follow-up interval for assessment of fusion was 26.6 months (range, 6–46 months). The usage of recombinant bone morphologic protein was higher in the mTLIF group (50% vs. 12%). Mean fusion rate from 16 studies (716 patients) of open TLIF was 90.9%, whereas mean fusion rate from 8 studies (312 patients) of mTLIF was 94.8%. Complication rate was 12.6% and 7.5% for open and mTLIF, respectively. Conclusion. Fusion rates for both open and mTLIF are relatively high and in similar ranges. Complication rates are also similar, with a trend toward mTLIF having a lower rate. This analysis provides clear benchmarks for fusion rates in open and mTLIF procedures for spine surgeons.Study Design. A quantitative meta-analysis was conducted on published studies reporting fusion rates after open or minimally invasive/mini-open transforaminal lumbar interbody fusion (TLIF) procedures for single or multilevel degenerative disease including stenosis with spondylolisthesis and degenerative disc disease. Objectives. The primary aim of this study was to establish benchmark fusion rates for open TLIF and minimally invasive TLIF (mTLIF) based on published studies. A secondary goal was to review complication rates for both approaches. Summary of Background Data. Lumbar fusion for the treatment of degenerative disease has evolved from a purely posterior noninstrumented approach to a combination of anterior and/or posterior surgery with instrumentation. The increasingly popular transforaminal approach has advanced to incorporate minimally invasive spinal techniques. There currently exist no controlled comparisons between open TLIF and mTLIF. Methods. A Medline search was performed to identify studies reporting fusion rate on open TLIF or mTLIF with instrumentation. A database including patient demographic information, fusion rate, and complication rate was created. Fusion and complication rates were pooled according to whether TLIF was performed with open or minimally invasive technique. Publication bias was assessed with Eggers test, and adjustments were performed using Duval and Tweedies Trim and Fill algorithm. Results. Twenty-three articles were identified that fit inclusion criteria. In each of the 23 studies, TLIF was performed with pedicle fixation and fusion was evaluated using radiograph or computed tomography scan at minimum 6-month follow-up. Overall, the studies included 1028 patients, 46.8% of which were female. The mean age of all patients was 49.7 (range, 38–64.9), and mean follow-up interval for assessment of fusion was 26.6 months (range, 6–46 months). The usage of recombinant bone morphologic protein was higher in the mTLIF group (50% vs. 12%). Mean fusion rate from 16 studies (716 patients) of open TLIF was 90.9%, whereas mean fusion rate from 8 studies (312 patients) of mTLIF was 94.8%. Complication rate was 12.6% and 7.5% for open and mTLIF, respectively. Conclusion. Fusion rates for both open and mTLIF are relatively high and in similar ranges. Complication rates are also similar, with a trend toward mTLIF having a lower rate. This analysis provides clear benchmarks for fusion rates in open and mTLIF procedures for spine surgeons.

Three-dimensional and 2-dimensional endoscopic exposure of midline cranial base targets using expanded endonasal and transcranial approaches.

OBJECTIVEEndoscopic endonasal approaches provide an access method to the midline cranial base. To integrate these approaches into neurosurgical practice, the extent of their anatomic exposure must be compared with that provided by more traditional transcranial approaches. METHODSTen fresh cadaver heads were studied. Both endonasal and transcranial approaches to the midline cranial base were performed. The midline cranial base was divided into several areas, and the relative exposure provided by each approach was described and presented in both 2-dimensional and 3-dimensional images. Limitations and advantages of each approach are discussed. RESULTSThe endonasal approaches achieved a direct and wide exposure of the midline extracranial and intracranial cranial base anatomy. The main lateral limitations of the endonasal approaches were the optic nerves, lateral cavernous sinus, vidian nerve, internal carotid artery, abducens nerve in Dorellos canal, jugular tubercle, and hypoglossal canals. Limitations of the transcranial approaches were the neurovascular structures which lie in the operative corridor and create narrow working spaces. CONCLUSIONThe endonasal approaches achieve a direct and wide exposure of the midline cranial base bilaterally. Lateral exposure, beyond the cranial nerves and carotid artery, are challenging. Transcranial approaches are limited by the narrow corridors provided by the cranial nerves, and they do not visualize the contralateral paramedian cranial base very well. Three-dimensional endoscopes augment the spatial orientation and may improve patient safety and the learning curve for endoscopic approaches to the midline cranial base.

Endoscopic endonasal minimal access approach to the clivus: case series and technical nuances.

BACKGROUND The endoscopic endonasal transclival approach is a novel minimal-access method of managing clival pathology. Limited cases have been published. OBJECTIVE To summarize our clinical experience with this approach and discuss technical nuances. METHODS We retrospectively reviewed a prospective database of 250 endoscopic, endonasal skull base surgeries. Patients in whom a transclival approach was performed were identified. Extent of resection, complications, and clinical outcome were analyzed. RESULTS Seventeen patients underwent 21 procedures. Pathology included chordoma, meningioma, hemangiopericytoma, enterogenous cyst, epidermoid, and metastasis. Lumbar drain was placed intraoperatively in 9 cases and maintained for approximately 2 days postoperatively. Mean operative time was 252.8 minutes. Intraoperative cerebrospinal fluid (CSF) leak occurred in 10 cases. Greater than 95% resection was achieved in 11 of 12 cases (92%) in which it was the surgical goal. The risk of postoperative CSF leak was 4.8% for all procedures, 9.1% for procedures with large skull base defect, and 0% if a gasket-seal closure was achieved. A nasoseptal flap was used in 2 patients. There was one perioperative infarct, one case of deep vein thrombosis, and one postoperative pulmonary embolus. Mean follow-up was 8.5 months. All but one patient with preoperative cranial nerve deficits improved at last follow-up. All patients were free of disease progression at last follow-up. CONCLUSIONS The endonasal endoscopic transclival approach provides a minimal-access approach to the ventral midline posterior fossa skull base. The risk of CSF leak is low if appropriate closure techniques are applied.

AAV-mediated delivery of the caspase inhibitor XIAP protects against cisplatin ototoxicity.

Hypothesis: Delivery of the gene encoding X-linked inhibitor of apoptosis (XIAP) using an adeno-associated viral (AAV) vector can protect against cisplatin-mediated ototoxicity. Background: Cisplatin is a widely used chemotherapeutic agent with significant ototoxic side effects. One possible mechanism of toxicity is apoptotic death of many cochlear cell types. Acute treatment with inhibitors of caspases- enzymes critical for apoptosis- has been shown to prevent hearing loss in vivo, but is too short-acting for therapeutic use. Gene therapy provides a specific and chronic means of delivering potential therapeutic gents. Introducing an anti-apoptotic gene into the cochlea could provide long-term prophylaxis against the ototoxic effects of cisplatin. Method: Two groups of rats were treated with unilateral injection into the round window of AAV harboring a gene encoding either XIAP or green fluorescent protein (GFP). After at least two months of gene expression, auditory-brainstem-response (ABR) threshold shifts and outer-hair-cell (OHC) number were measured in these two groups of animals after 72-hour treatment with cisplatin. Results: Consistent with previous reports, uninjected and AAV.GFP-injected ears displayed profound ABR threshold elevations and OHC loss after cisplatin treatment. Ears that had been injected with AAV encoding XIAP, however, were significantly protected from these effects: cisplatin-induced ABR-threshold shift and hair-cell loss were attenuated by as much as 78% and 45%, respectively, when compared with contralateral (untreated) ears. Conclusion: XIAP delivery to the cochlea can protect against the audiometric changes and hair-cell loss associated with cisplatin ototoxicity. The efficacy, specificity, and duration of the protective effects make this a potentially attractive therapeutic paradigm.

Understanding history, and not repeating it. Neuroprotection for acute ischemic stroke: From review to preview

BACKGROUND Neuroprotection for ischemic stroke is a growing field, built upon the elucidation of the biochemical pathways of ischemia first studied in the 1970s. Beginning in the early 1990s, means by which to pharmacologically intervene and counteract these pathways have been sought, though with little clinical success. Through a comprehensive review of translations from laboratory to clinic, we aim to evaluate individual mechanisms of action, while highlighting potential barriers to success that will guide future research. METHODS The MEDLINE database and The Internet Stroke Center clinical trials registry were queried for trials involving the use of neuroprotective agents in acute ischemic stroke in human subjects. For the purpose of the review, neuroprotective agents refer to medications used to preserve or protect the potentially ischemic tissue after an acute stroke, excluding treatments designed to re-establish perfusion. This excludes mechanical or pharmacological thrombolytics, anti-thrombic medications, or anti-platelet therapies. RESULTS This review summarizes previously trialed neuroprotective agents, including but not limited to glutamate neurotransmission blockers, anti-oxidants, GABA agonists, leukocyte migration blockers, various small cation channel modulators, narcotic antagonists, and phospholipid membrane stabilizers. We outline key biochemical steps in ischemic injury that are the proposed areas of intervention. The agents, time to administration of therapeutic agent, follow-up, and trial results are reported. DISCUSSION Stroke trials in humans are burdened with a marked heterogeneity of the patient population that is not seen in animal studies. Also, trials to date have included patients that are likely treated at a time outside of the window of efficacy for neuroprotective drugs, and have not effectively combined thrombolysis with neuroprotection. Through an evaluation of the accomplishments and failures in neuroprotection research, we propose new methodologies, agents, and techniques that may provide new routes for success.

Embolectomy for stroke with emergent large vessel occlusion (ELVO): report of the Standards and Guidelines Committee of the Society of NeuroInterventional Surgery

Stroke is the leading cause of adult disability in North America and is the fifth most common cause of death.1 ,2 The natural history of patients with acute ischemic stroke and occlusion of a major intracranial vessel such as the internal carotid artery (ICA), middle cerebral artery (MCA), or basilar artery is dismal, with high rates of mortality and low rates of disability-free survival.3 ,4 We introduce the term ‘Emergent Large Vessel Occlusion (ELVO)’ to describe this clinical scenario. Among acute ischemic stroke, ELVO accounts for the greatest proportion of patients with long-term disability. For the past two decades the use of endovascular therapy has been performed in many centers across the world. The therapies have spanned from infusion of thrombolytic agents5 ,6 to mechanical embolectomy with the introduction of first-generation devices,7 ,8 aspiration-based embolectomy techniques,9 ,10 and the use of stent-retriever based procedures.11 ,12 However, these embolectomy trials were single-arm trials demonstrating safety of the procedure and technique or superiority over another, without direct comparison with standard medical therapy alone. In the past 3 years, several major trials have been published comparing endovascular therapy with standard medical therapy alone. The purpose of this document is to summarize the results of these trials and synthesize the level of evidence supporting the use of embolectomy in patients with ELVO. This document was prepared by the Standards and Guidelines Committee of the Society of NeuroInterventional Surgery, a multidisciplinary society representing the leaders in the field of endovascular therapy for neurovascular disease. The strength of the evidence supporting each recommendation was summarized using a scale previously described by the American Heart Association. ### Role of intravenous thrombolysis In 1996 the FDA approved the use of recombinant tissue plasminogen activator (tPA) for the treatment of acute ischemic stroke …

Factors Contributing to Ventriculostomy Infection

OBJECTIVE Catheter-related infection remains a cause of morbidity in the use of external ventricular drains (EVDs). The aim of this retrospective single-center study was to assess the rate and factors related to ventriculostomy infections in the setting of the published literature. METHODS Patients that underwent EVD placement in a single-center were retrospectively reviewed. Diagnosis, treatment, hospital course, and infection-related data were collected and analyzed in reference to ventriculitis rates. The protocols for EVD placement and maintenance were reviewed. RESULTS Of 343 patients, 12 acquired an EVD infection. No significant differences existed between those with and without ventriculitis for age, sex, underlying diagnosis, or concomitant systemic infection. Although not significant, concomitant systemic infection existed in 4.7% of patients with ventriculitis versus 1.5% without. There was a significant difference in length of EVD placement in patients with ventriculitis (20.9 ± 15.3 days) versus those without (12.1 ± 18.2; P = 0.005). Coagulase-negative Staphylococcus and Staphylococcus aureus represented the most commonly associated pathogens. With an overall cumulative incidence of 3.5%, our rate compared favorably to the published literature (cumulative incidence 9.5%; range, 3.9%-23.2%). CONCLUSIONS Catheter-related infection remains an important complication of EVD placement. Of factors evaluated, length of time of catheter placement has the most notable relationship to infection incidence, suggesting that early drain removal should be a goal whenever medically appropriate.