Subject: Tumor
Title: Research Category Infected Rathkeís Cleft Cysts: Distinguishing Factors and Factors Predicting Recurrence
Authors: Jahangiri Arman
Introduction: Rathkeís cleft cysts (RCC) are benign sellar lesions that are generally asymptomatic but sometimes warrant transsphenoidal drainage. Small case reports have described infected RCCs, but this phenomenon remains uncharacterized. We reviewed RCCs over 23 years at our institution to determine factors predicting infection and recurrence.
Methods: We retrospectively reviewed MRIs, labs, microbiology, and pathology of 176 RCC patients (1985-2008) who underwent initial operation at our institution (n=170) or at another institution followed by recurrence managed at our institution (n=6).
Results: There were 3 RCC categories: cysts cultured intraoperatively during initial surgery (n=21); cysts not cultured during initial surgery but cultured during subsequent surgery (n=9); and cysts that were never cultured (n=146). Cultured cysts were larger (1.6 cm vs. 1.2 cm, P=0.002) and had more frequent pituitary dysfunction (76% vs. 30%; P<0.00001) than noncultured cysts. Restricted diffusion was also more common in cultured cysts (50% vs. 0%, P=0.02). Of cysts cultured at initial or subsequent surgery, 48% and 44%, respectively, had positive cultures (n=14) and were treated with antibiotics. The most common organisms were Staphylococcus epidermidis (64%) and Propionibacterium acnes (57%). Kaplan-Meier recurrence rates were 13% (culture-positive/antibiotic-treated), 31% (culture-negative/nonantibiotic-treated), and 9% (non-cultured) (P=0.002 cultured versus non-cultured; P=0.002 culture-negative/non-antibiotic-treated versus non-cultured; P=0.5 culture-positive/antibiotictreated versus non-cultured).
Conclusions: In our series, suspected RCC infection, independent of culture results, is a strong predictor of recurrence and may warrant antibiotic treatment. With antibiotic treatment, the recurrence rate of infected RCC approaches that of non-infected cysts. The higher recurrence rates reported in other series may reflect under-recognition of occult infection.
Keywords: Rathke’s cleft cysts,
Objectives: 1. Distinguish factors predicting infected Rathke’s cleft cysts (RCC) from uninfected cases. 2. Take into account the impact of antibiotic treatment on infected RCC in relation to its recurrence rate. 3. Determine when to treat RCC patients suspected of purulence with antibiotics.
Subject: Functional
Title: Intrathecal Baclofen Therapy for Multiple Sclerosis
Authors: Paul A. House; Joel D. MacDonald
Introduction: We have used intrathecal baclofen delivered via implanted programmable pump to manage spasticity and pain related to multiple sclerosis.
Methods: We retrospectively reviewed operative records from a single institution over a 5 year period form 2005 to 2010. We identified 30 adult patients who underwent placement of baclofen pumps for MS. Preoperative complaints typically included pain and lower extremity spasticity.
Results: All patients experienced significant improvement in preoperative symptoms. No major procedural complications were identified. Some patients noted a decline in ambulatory function due to loss of postural tone and lower extremity spasticity. All patients indicated subjective improvement in pain. Average dose tended to be lowere than that for other varieties of spasticity.
Conclusions: Intrathecal baclofen therapy is feasable and safe for management of spasticity and pain related to multiple sclerosis.
Keywords: Baclofen, Intrathecal pump, Multiple Sclerosis
Objectives: Participants will be able to discuss intrathecal baclofen therapy and its use in multiple sclerosis. Participants will be able to discuss the technical aspects of intrathecal pump placement. Participants will be able to discuss risks and benefits of ITB for MS patients.
Subject: Tumor
Title: Infected Rathke’s Cleft Cysts: Distinguishing Factors and Factors Predicting Recurrence
Authors: Arman Jahangiri; Mathew C. Tate; Lewis S. Blevins; Sandeep Kunwar; Howard Morgan; Manish K. Aghi
Introduction: Rathke’s cleft cysts (RCC) are benign sellar lesions that are generally asymptomatic but sometimes warrant transsphenoidal drainage. Small case reports have described infected RCCs, but this phenomenon remains uncharacterized. We reviewed RCCs over 23 years at our institution to determine factors predicting infection and recurrence.
Methods: We retrospectively reviewed MRIs, labs, microbiology, and pathology of 176 RCC patients (1985-2008) who underwent initial operation at our institution (n=170) or at another institution followed by recurrence managed at our institution (n=6).
Results: There were 3 RCC categories: cysts cultured intraoperatively during initial surgery (n=21); cysts not cultured during initial surgery but cultured during subsequent surgery (n=9); and cysts that were never cultured (n=146). Cultured cysts were larger (1.6 cm vs. 1.2 cm, P=0.002) and had more frequent pituitary dysfunction (76% vs. 30%; P<0.00001) than noncultured cysts. Restricted diffusion was also more common in cultured cysts (50% vs. 0%, P=0.02). Of cysts cultured at initial or subsequent surgery, 48% and 44%, respectively, had positive cultures (n=14) and were treated with antibiotics. The most common organisms were Staphylococcus epidermidis (64%) and Propionibacterium acnes (57%). Kaplan-Meier recurrence rates were 13% (culture- positive/antibiotic-treated), 31% (culture-negative/nonantibiotic-treated), and 9% (non-cultured) (P=0.002 cultured versus non-cultured; P=0.002 culture-negative/non-antibiotic-treated versus non-cultured; P=0.5 culture- positive/antibiotictreated versus non-cultured).
Conclusions: In our series, suspected RCC infection, independent of culture results, is a strong predictor of recurrence and may warrant antibiotic treatment. With antibiotic treatment, the recurrence rate of infected RCC approaches that of non-infected cysts. The higher recurrence rates reported in other series may reflect under-recognition of occult infection.
Keywords: rathke’s cyst, pituitary,recurrence, infection
Objectives: 1. Distinguish infected RCC from non-infected cases. 2. Understand the importance of infected RCC and its impact on recurrence. 3. Provide the appropriate treatment for infected RCC following drainage of cyst (i.e. antibiotics).
Subject: Socioeconomic
Title: Treatment With Clinical Benefit
Authors: Sanjay N. Misra
Introduction: Regulations applying to the utilization of materials and treatments for patients are enforced by various regulatory institutions. These institutions provide detailed guidelines for the ethical use and outcome determination for clinical treatment options and technologies.
Methods: Case analysis of two technologies in use for the clinical treatment of patients is provided. One material for use in spinal surgery despite widespread clinical utilization has failed to demonstrate any clinical benefit and therefore is rejected for use for its proposed indications based on federal regulation. A cranial implant in common clinical use comes under review for a proposed new indication and fails to meet all clinical benefit outcomes but under regulation is approved for conditional availability to the population
Results: The regulatory process for the evaluation of new technologies for the treatment of patients, in the context of these case studies is discussed . The cases illustrate the importance in neurosurgical planning of critical thinking and awareness of regulations that impact on neurosurgical clinical practice. The cases highlight the restrictions that may in place for new technologies and the rationale for such restrictions.
Conclusions: Legal regulatory considerations guide the use of treatments as indicated in the labeling. The use of treatments is under the jurisdiction of regulatory institutions with mandated reporting obligations for physicians, in the application of evolving technologies to patient care. Awareness of this structure is critical for best medical practice.
Keywords: Neurosurgery, Regulations, Indication, Guidance
Objectives: Understand regulatory considerations for determining the safety of drugs and devices. Awareness of safety regulations for the establishment of treatments. Recognize the value of treatment labeling and disclosed outcomes in determining patient treatment options.
Subject: Spine
Title: Cervical Syrinx Due to an Occult Meningioma Band
Authors: Jeremy Phelps; Howard Yonas
Introduction: Syringomyelia is a well documented condition that can arise from numerous causes including blockage of cerebrospinal fluid circulation at the fourth ventricle (e.g. Arnold Chiari malformation, basilar invagination, or arachnoid cysts), direct spinal cord injury (e.g. trauma, radiation necrosis, ischemic injury, and transverse myelitis), spinal dysraphism, intramedullary tumors, or extramedullary tumors.
Methods: The patient is a 49-year-old male with a ten year history of progressive neck and arm pain. The pain was described as ìburningî and was located primarily in the hands. He reported numbness and weakness in the C6-8 distributions. Physical exam findings demonstrated decreased strength in bilateral deltoids, triceps, biceps, and intrinsic hand muscles as well as decreased pinprick sensation in the C5-C8 distributions. An cervical spine MRI with and without contrast demonstrated a septated syrinx from C2-T1 with the largest diameter at the C5-6 level. No abnormal enhancement, Chiari malformation, or spinal dysraphism was visualized.
Results: The patient was taken for the placement of syringe-subarchnoid shunt. Upon dural opening, a cluster of adhesions surrounding and constricting the posterior aspect of the spinal cord were noted. The adhesions were dissected from the cord resulting in the cord resuming a more natural anatomic position. The adhesion clusters were sent for pathologic analysis. The decision was made to forgo the placement of the shunt and the wound was closed without event. The pathological specimen was consistent with a WHO Grade I fibroblastic meningioma. Cells are immunoreactive for epithelial membrane antigen (EMA) in a membranous pattern, smooth muscle actin (SMA), and vimentin. Glial fibrillary acidic protein (GFAP), Bcl-2, S-100, CD56, neurofilament, desmin, CD34. and keratin AE1-AE3 were negative. A Ki-67 proliferation index is low (<1%), but scattered tumor cell nuclei show strong immunoreactivity. Postoperatively, the patientís radicular pain resolved allowing him to stop narcotic pain medications. Sensation improved but remained slightly diminished in the left C6-8 distributions. The weakness in the hands resolved completely. Post-operative MR imaging studies demonstrated a resolution of the cervical syrinx and a small pseudomeningocele extending into the regional posterior soft tissues.
Conclusions: Meningiomas account for approximately 25% of all spinal tumors. Approximately 80% of spinal meningiomas are located in the thoracic spine, followed by cervical spine (15%), lumbar spine (3%), and the foramen magnum (2%). Spinal meningiomas are often located laterally or dorsolaterally in the thoracic spine and ventrally located in the cervical spine and foramen magnum. Spinal meningiomas differ from intracranial meningiomas by their slightly greater proclivity for psammomatous change Meningotheliomatous and transitional features are most common in spinal lesions. Spinal meningiomas are typically globoid and vary in consistency depending on the extent of calcification. MRI imaging typically demonstrates homogeneous intense enhancement and lesions isointense to spinal cord on both T1-weighted and T2-weighted images. This case demonstrates unique features of a non-contrast enhancing meningioma causing an atypical type of constriction of the spinal cord. Moreover, the pathological characteristics were somewhat atypical for spinal meningiomas.
Keywords: Cervical Syrinx Meningioma
Objectives: At the completion of the session or demonstration, participants should be able to (1) discuss the different conditions which can lead to a cervical syrinx and (2) discuss the common features of spinal meningiomas.
Subject: Tumor
Title: Intracranial Meningiomas in Trans-Sexual Patients on Cross-Sex Hormone Therapy: Case Reports and Review of the Literature
Authors: Jeremy Phelps; Rafael Medina-Flores; Howard Yonas
Introduction: Cross-sex hormonal therapy is an important component of the endocrine regimen in trans-sexual patients. The role of sex hormones in meningioma development has been proposed as one explanation of the increased incidence of meningiomas among women with a history of hormone replacement therapy and long-acting contraceptive use. A previous case report has suggested a causal association between meningioma growth and cross-sex hormone therapy. We report a second case of meningioma and the first incidence of tumor recurrence following gross total resection in a trans-sexual patient on hormone replacement.
Methods: A 65-year-old male-to-female transsexual presented with worsening headaches, frequent falls, and difficulty speaking. Imaging studies demonstrated a 3.2 x 3.2 x 4.0 cm left sphenoid wing meningioma destroying the lateral orbital wall and causing left to right midline shift. A near gross total resection was performed and post-operative imaging displayed minimal residual mass. The patient had dramatic resolution of symptoms following the procedure. Pathology demonstrated a clear cell meningioma, WHO grade 2. Progesterone receptor immunoreactivy for was strongly positive and estrogen receptor reactivity was negative. Despite counseling to discontinue hormone therapy, the patient continued on a regimen of 100 micrograms of estradiol per day.
Results: The symptoms of headache and speech difficulties began to return approximately one year after the initial resection and repeat MR imaging demonstrated tumor regrowth. The patient was taken for a second resection. Pathological studies again demonstrated a clear cell meningioma, WHO grade 2.
Conclusions: Although the incidence of meningioma development while on cross-sex hormonal therapy is rare, there is a growing literature indicating a possible causal connection. Our patient is the second reported case of meningioma occurrence while on cross-sex hormonal therapy. While no direct causal relationship can definitively be made at this time, neurosurgeons should be familiar with the growing incidence of cross-sex hormonal therapy in trans-sexual patients and its reported connection to meningiomas. A brief review of the current literature concerning hormone therapy and its effect on meningiomas will be undertaken.
Keywords: Meningioma, Hormone Supplementation, Transsexual
Objectives: At the completion of the session, participants should be (1) aware of reported connections between meningiomas and cross-sex hormonal therapy and (2) able to discuss the current literature concerning the effects of hormone therapy on meningiomas.
Subject: Spine
Title: DIrect C2 Pedicle Screw Fixation for Hangman’s Fracture
Authors: Joel D. MacDonald
Introduction: Halo immobilization for C2 Hangman’s fracture is both a morbid and not infrequently ineffective treatment. Directs screw fixation of these fractures facilitates rapid healing and preservation of motion.
Methods: A surgical procedure database for a single surgeon, single institution was review for a 2 year period from 2008 to 2010. Three patients were identified that sustained unstable C2 Hangman’s fracture and surgical treatment. Bilateral screws were placed in each case. Intra-operative stereotactic CT guidance (O-Arm) was used. follow-up imaging was reviewed to establish healing and clinical notes were used to determine outcome.
Results: There were no operative complications and no new post-operative neurological deficits. Each patient sustained solid union of the fracture segment as documented by late follow-up CT and plain films. Each patient experience acceptable preservation of cervical range of motion.
Conclusions: Direct C2 pedicle screw fixation offers an option for treatment of traumatic Hangman’s fracture. Full motion can be preserved while avoiding the morbidity of a halo vest.
Keywords: Hangman’s fracture, screw fixation
Objectives: Participants will be able to discuss the anatomy of a Hangman’s fracture. Participants will be able to discuss the advantages and disadvantages of halo brace and surgical fixation of this fracture type. Participants will be able to discuss the technical aspect of C2 pedicle screw placement.
Subject: Pediatrics
Title: Use of the Trocar for Management of the Peritoneal Shunt Catheter-A 20 Year Experience
Authors: S David Moss
Introduction: Hydrocephalus and the need for cerebrospinal fluid diversion has been a complicated problem for neurosurgeons and had made up a large bulk of the practice of most pediatric neurosurgeons; however, large studies examining the safety and reliability of the technical aspects of the procedures are still lacking. Use of the peritoneal trocar in the management of the peritoneal shunt catheter in the pediatric patient population over 20 years in one practice is presented. The literature is reviewed. The technique is described and caveats learned over course of use are presented in comparison to published ëopení catheter placements. The literature is reviewed. The use of the endoscope and trocar in removal of migrated and retained peritoneal catheters is described. The procedure is shown to be effective and safe in the majority of patients.
Methods: A retrospective chart review of cases performed at Phoenix Childrenís Hospital by the principle investigator from 1990 to 2010 was performed. A prospective database was maintained during this time from which data were retrospectively gleaned during our study.
Results: During the study period, there were __ complications related to the use of the peritoneal trocar in pediatric shunting procedures, leading to the observed complication rate of __%. Data was obtained from operative notes and cases were identified by an early return to the operating room and operative note indications that a complication had occurred when describing the indication for surgery.
Conclusions: From our experience and review of the literature, it appears as if the peritoneal trocar may be the safest option pediatric neurosurgeons have for abdominal access for cerebrospinal fluid diversion in most patients. Reviewing the complications, suggestions regarding complication avoidance and patient selection are discussed.
Keywords: trocar, hydrocephalus, shunt
Objectives: Identify patients appropriate for use of the trocar for shunt catheter placement. Identify the safest approach for abdominal catheter placement. Understand the technique for trocar insertion into the abdominal cavity.
Subject: Tumor
Title: Craniofacial approaches to large juvenile angiofibromas
Authors: Yashar Kalani
Introduction: Craniofacial approaches provide excellent exposure to lesions in the anterior and middle cranial fossa. Herein we review our experience with combined craniofacial approach for resection of large juvenile nasopharyngeal angiofibroma (JNA), a highly vascular pediatric tumor.
Methods: Between 1992 and 2009, 22 patients (all male with a mean age of 15 years [range 9ñ27 years]) underwent 30 craniofacial procedures. These cases were reviewed retrospectively.
Results: Gross-total resection of 19/22 (86%) lesions was achieved in either a staged or single surgery. Two patients required staged surgeries. Craniofacial operations involve radical resection of skull base and facial bones, hence they are bloody with an average blood loss of 1482 mL (range 400-4900 mL). The average duration of hospitalization for these procedures was 8.2 days (range 3-20 days). The rate of recurrence in our series is 32% (7/22), with recurrence occurring on the average 12.4 months after the first resection. The cases of recurrence were all treated with repeat surgery and/or radiation therapy. We utilized pre-operative embolization in every case we operated on to decrease morbidity. Complications occurred in 9 of the 22 patients (41%) and mostly consisted of cerebrospinal fluid leakage (23%). The average follow-up for our series was 27.7 months (range 2-144 months). The surgery-related mortality rate was 0%. Based on their pre-operative (mean 90) and postoperative (mean 90) Karnofsky Performance Scale scores, 100% of patients improved or remained the same.
Conclusions: Skull base lesions can be resected using many different approaches. Craniofacial approaches provide a safe and robust window into anterior and middle cranial fossa lesions. At the Barrow Neurological Institute (BNI), we combine pre-operative embolization, with an expert multidisciplinary skull base team for the treatment of these lesions. Recurrences are treated by combined endovascular/vascular approaches and radiation therapy. Our experience shows that craniofacial approaches, notably the transfrontal-nasal-orbital approach provides an excellent avenue for the resection of massive juvenile nasopharyngeal angiofibromas with little morbidity and no mortality.
Keywords: juvenile nasopharyngeal angiofibroma, approach, craniofacial surgery
Objectives: Understand treatment options for JNAs. Cite complication rates for transfacial approaches to anterior and middle skull base. Understand the pathophysiology of JNAs.
Subject: Tumor
Title: Stereotactic Brachytherapy for Recurrent Sellar Masses
Authors: Erika A Petersen; Tony Whitworth; Barbara Schultz; Robert Timmerman
Introduction: The implantation of radioactive sources within tumors using stereotactic techniques has been applied to intracranial tumors since the 1950s. While stereotactic radiosurgery has gained popularity as a safe, non-invasive treatment for intracranial tumors, there remains a role for interstitial brachytherapy, particularly in the management of large tumors not suitable for radiosurgery. Advances in stereotactic imaging and computation of dose algorithms have resulted in improved safety and effectiveness in delivering radiation into the tumor target using permanently implanted low-activity sources. The ability to conform the radiation field such that the maximum dose targets the tumor while protecting surrounding structures including the optic nerves and the cranial nerves within the cavernous sinus has led to the investigation of brachytherapy as a treatment of recurrent sellar masses for which all other therapies have failed.
Methods: Four patients with history of multiple recurrences of tumor were identified as candidates for brachytherapy after all surgical and adjuvant therapies had failed to control tumor progression. Preoperative dose-planning by the radiation oncology team identified targets for Iodine-125 seed implantation; one or two seeds were used depending on the tumor distribution and the radiation delivery. Stereotactic placement of the seeds through a transsphenoidal endonasal approach was performed using the Leksell Series G frame and MRI images. Intraoperative fluoroscopic images confirmed placement of the seeds at target. Patients were followed at three-month intervals with MRI scans and clinical examinations.
Results: There were no intraoperative or immediate postoperative complications from the procedure. Length of follow-up ranged from 3 to 10 months. One patient died eight months after the procedure from unrelated causes. MRI imaging at 3 months after implantation showed stable or decreased tumor size in all four patients. In two patients there was new abnormal FLAIR signal in regions adjacent to the tumor, but the patients were asymptomatic. No patient demonstrated progression of clinical symptoms including further loss of vision.
Conclusions: Stereotactic brachytherapy remains an alternative for treatment of recurrent sellar masses, particularly those that are too large for radiosurgical treatment and for whom resection options are limited. The rapid fall-off of dose beyond the target volume minimizes the chance of radiation injury while a potent dose is delivered to the tumor. In our small series, tumor progression was controlled, and there was some evidence of decreased tumor size. Long-term follow-up for safety and tumor control will continue.
Keywords: tumor, radiotherapy, transsphenoidal
Objectives: 1) Discuss the surgical technique for intrasellar brachytherapy 2) Review clinical indications for the procedure and patient selection 3) Compare the benefits and risks of brachytherapy with surgical resection and other radiation modalities
Subject: Cerebrovascular
Title: Positive Predictive Value of a Trial Balloon Occlusion Protocol in the Carotid Circulation
Authors: Jonathan A. White; Kim Rickert; Babu Welch; Lee Pride; Novakovic Robin; John Truelson
Introduction: The carotid artery must occasionally be sacrificed in the treatment of complex cerebrovascular disease, skull base tumors and head and neck cancers. Accurately predicting which patients can tolerate such a vessel sacrifice remains a challenge.
Methods: This study is a retrospective review of patients who underwent a pre-operative trial balloon occlusion protocol (TBO) of the carotid artery prior to vessel sacrifice. The protocol consisted of inflation of a catheter mounted balloon in the internal or common carotid artery for at least fifteen minutes. Serial neurological examinations were conducted and 28 mCi of Technetum Tc99m (Neurolite, Bristol-Myers Squibe, Billerica, Massachusetts) was injected and later tomographic images were obtained.
Results: Between 2004 and 2010, 95 patients had a TBO. Forty six were for neck or skull base mass, 49 were for primary vascular pathology. Two patients (2.1%) suffered a stroke as a result of the TBO. Of the 95 patients who had a TBO, 12 underwent later vessel sacrifice. None of these patients developed a neurological deficit during the time of balloon inflation nor did they show asymmetry of perfusion on their post Neurolite tomogram. Four of these patients went on to stroke. Of the four strokes two were clearly attributable to the vessel sacrifice, one was obviously not related and one was equivocal for a positive predictive value ranging from 75% to 83%.
Conclusions: Even with extensive pre-operative testing, vessel sacrifice carries significant risk. The morbidity and positive predictive value of additional strategies such as induced hypotension should be evaluated.
Keywords: Carotid, vessel sacrifice, nuclear medicine, stroke
Objectives: Understand the role of carotid sacrifice in treating cervical or cerebral pathology. Analyze risk associated with carotid sacfifice. Create a protocol for vessel sacrifice in your own practice.
Subject: Spine
Title: Intraspinal neuroendoscopy for spinal subarachnoid and subdural hemorrhage
Authors: Atif Haque; John B. McGowan; Anthony Whittemore; Howard Morgan; Kevin Morrill
Introduction: Intrathecal hemorrhages are relatively rare entities encountered by neurosurgeons. The authors present two cases of patients harboring symptomatic intraspinal hemorrhages and report their experience with attempted minimally-invasive, endoscopic-assisted evacuation of these hemorrhages using a small flexible endoscope, not specifically intended for this application, but readily available at many hospitals.
Methods: In two adult males harboring intraspinal hemorrhages, one with a complete spinal cord injury and the other with progressive deficits, limited laminectomies were performed to expose the thecal sac. After opening the dura, the intrathecal compartment was explored using a flexible 7.5 French outer diameter endoscope intended for choledochoscopy. Continuous irrigation was used to clear encountered hematoma.
Results: In the first patient with a complete injury following lumbar puncture while being anticoagulated, laminectomies at only 2 levels at the cervicothoracic junction provided access to nearly the entire thoracic spine. The loose, mostly dorsally located hemorrhagic materials were irrigated clear without identification of a bleeding source. Postoperative MRI showed near-total resolution of his subdural and subarachnoid hemorrhage. The patient, however, regained no neurological function to his lower extremities. In the second patient with a progressive injury, formed clot was seen ventral to the spinal cord but could not be adequately evacuated endoscopically and required further laminectomies at adjacent levels for decompression. The patient regained a significant amount of function in his lower extremities postoperatively.
Conclusions: Intraspinal neuroendoscopy using small, flexible endoscopes that are indigenous to many, if not most, institutionsí operating rooms can safely be used as an adjunct to verify and evacuate selected cases of intraspinal subarachnoid and subdural hemorrhages. By employing endoscopic-assistance, surgical exposures can be limited, blood loss minimized, and operative times shortened, especially in cases of dorsally-situated, loosely packed hematomas.
Keywords: endoscopy, myeloscopy, spinal subdural hematoma, spinal subarachnoid hemorrhage
Objectives: Explore the potential role of intraspinal neuroendoscopy in the evacuation of spinal intrathecal hemorrhages. Appreciate the safety of small, flexible endoscopes in spinal navigation. Understand the potential reduction in surgical morbidity using this minimally-invasive technique.
Subject: Functional
Title: Multi-scale Comparison of Recording Devices in Human Neocortex
Authors: Paul A. House; Kyle Thomson; Bradley Greger
Introduction: Several devices exist for performing electrophysiological neurological recordings directly from the neocortex. Devices range from microwires to centimeter sized electrocorticography pads. Exactly what type of information can be reliably obtained from different types of recording devices has not been directly compared.
Methods: Patients undergoing intracranial electrocorigaphy procedures for seizure onset zone localization were also implanted with electrocorticographic grids made from non-penetrating microwires or penetrating microelectrode arrays. Materials were FDA approved and the study was undertaking with IRB approval. Correlation analysis was run on epochs of 5 minutes of data. A fit line was used for each electrode to determine the drop in correlation per millimeter. The three frequency bands investigated were the Beta band(12-30 Hz), Gamma (30-80 Hz) and High Frequency Oscillations band(100-600 Hz).
Results: Correlations were mapped graphically for each type of device and different spatial resolution is observed for different frequency bands. A line-fit is produced showing the degree of correlation expected for electrophysiological recordings across the neocortex.
Conclusions: These results show channel independence varies greatly with electrode type and scale. For neuroprosthetic applications the change in correlation based on distance can be used as a design input for future recording devices.
Keywords: microelectrodes, electrocorticography, neuroprosthetics
Objectives: …appreciate that different types of neuronal information are required for various future prosthetics applications. …appreciate that different measures of information correlation can be used to evaluate recording systems …appreciate that comparison of recording systems in humans have been rarely described to date.
Subject: Trauma
Title: Use of Pharmacologic Thromboprophylaxis After Traumatic Brain Injur
Authors: Andrew S Levy; Kristin Salottolo
Introduction: The use of pharmacologic thromboprphylaxis (PTP) following traumatic brain injury (TBI) is an importiant and contraversial topic that neurosurgeons, trauma surgeons, and critical care specialists struggle with on a frequent basis. There is currently insuficient evidence to determine in which patients with TBI PTP should be used, and when. The purpose of this study is to determine if PTP increases the risk of intracranial hemorrhage (ICH) progression in patients with TBI, and if so, in which patients.
Methods: In a retrospective cohort study we reviewed patients admitted with TBI to a Level I Trauma Center over an 18 month period, and analyzed timing and use of PTP. We also reviewed CT reports and clinical parameters to evaluate for CT evidence of ICH progression, and for clinically significant ICH progression. DVT and PE rates were also evaluated. Patients were divided into two populations: those with a stable initial f/u CT (within 24 hours of admission), and those with ICH progression on the initial f/u CT. Independent risk factors for worsening CT findings were analyzed using logistic regression, including PTP use. Patient demographics, injury severity, and clinically significant hemorrhage progression were also analyzed. Timing of PTP was defined as early (< 72 hours), late (≥ 72 hours), or none.
Results: There were 340 patients with TBI and ICH on CT scans admitted during the study period. Intracranial hemorrhage progression occurred in 32.4% (n=110) of patients, of which 56.4% were considered clinically significant (n=62). In patients with progression of ICH on initial f/u CT (prior to PTP), predictors of subsequent hemorrhage progression include exposure to PTP (OR: 13.07, p=0.01), extradural/subdural hemorrhage (OR: 5.15, p=0.03), Glasgow coma score 3 ñ 8 (OR: 4.64, p=0.03), and BMI ≥ 25 (OR=4.32, p=0.03). PTP was not associated with an increased risk of ICH progression in patients with a stable initial f/u CT. Furthermore, there was no signifcant difference in the rate of DVT or PE between the TBI groups who recieved early PTP, late PTP, or no PTP.
Conclusions: These findings suggest that PTP use is associated with a 13-fold increased risk of subsequent/further hemorrhage progression in TBI patients who had hemorrhage progression on initial f/u CT. Conversely, PTP may be safe to administer early (36-72 hours) to TBI patients with a stable initial f/u CT.
Keywords: Traumatic Brain Injury, Pharmacologic Thromboprophylaxis, Lovenox, Intracarnial Hemorrhage
Objectives: Understand risk of DVT and PE in Trauma patients. Understand options and guidlines for the timing and use of phamacologic thomboprophylaxis in patients with TBI. Understand the risk of intracranial hemorrhage after pharmacologic thomboprophylaxis in patients with TBI.
Subject: Tumor
Title: Nanoparticle delivery of hypoxia-inducible factor-1 siRNA for inhibition of intracranial malignant gliomas
Authors: Randy L. Jensen; David L. Gillespie
Introduction: Hypoxia-inducible factor 1a (HIF-1α) induces transcription of glycolytic genes including carbonic anhydrase IX (CA IX) and glucose transporter- 1 (Glut-1) and angiogenic proteins like vascular endothelial growth factor (VEGF). HIF-1α expression is increased in human glioblastoma multiforme (GBM) compared to low-grade tumors. We have previously shown that HIF-1α inhibition decreases tumor growth in a flank glioma model. This study examines methods of anti HIF-1 siRNA delivery utilizing nanoparticle systems in an intracranial model and the effects on tumor angiogenesis and growth
Methods: We use siRNA directed against HIF- 1α in an intracranial luciferase reporter glioma model with the ability to measure HIF-1 activity and tumor growth in vivo. These molecules are delivered with a variety of nanoparticle delivery molecules we call multifunctional carrier (MFC) and chemically modified AccellTM siRNAs. Tumor growth was followed by luciferase activity over time and compared between various nanoparticle carrier molecules. We also examine local osmotic pump delivery and systemic therapy. At the end of treatment, tumors were removed and examined for expression of downstream-regulated molecules well as measures of angiogenesis and cellular proliferation.
Results: We demonstrated reduced tumor growth and HIF-1 activity in tumors treated with anti-HIF-1α siRNA delivered with our MFC nanoparticles compared to other carriers and negative control siRNA injections. No neurotoxicities were found. We also found reductions of HIF-1α, VEGF and GLUT-1 expression, as well as decreased MIB-1 index and decreased vascular density. Difficulties and future strategies of local delivery with osmotic pumps and systemic delivery utilizing tarteting moieties are discussed
Conclusions: Our preliminary results suggest that intracranially injected siRNA against HIF-1α complexed to a newly developed carrier might be used for treatment of malignant brain tumors. This needs to be further developed with more specific tumor targeting and possibly even systemic delivery strategies for future use of this treatment strategy.
Keywords: hypoxia, glucose, proliferation, vascularity
Objectives: Understand how inhibition of hypoxia-inducible factor-1 in malignant gliomas might be uses as a treatment strategy for patients with this disease
Subject: Spine
Title: Patient Crossover: The Achilles Heel of Randomized Surgical Trials
Authors: Joseph E Beshay
Introduction: Patient crossover presents significant difficulty in interpreting data in surgical randomized trials. There are several techniques available to mitigate this. These include analysis of data completed by intent to treat analysis, as treated analysis or per protocol analysis. A thorough understanding of each analytical model and its associated limitations is of vital importance to surgeons.
Methods: Evidence based medicine review incorporating data from SPORT trials
Results: N/A
Conclusions: Patient crossover makes interpretation of data more difficult. Each analytical model available to interpret the data has signifcant shortcomings. An understanding of each model will allow surgeons to come to more accurate conclusions regarding data presented in which there is crossover.
Keywords: Evidence based Medicine, Statistics, Crossover
Objectives: Understand the limitations of randomized surgical trials in the setting of patient crossover.