Subject: Socioeconomic
Title: Sham Controlled Trials–The Next Step in Evidence-Based Surgery?
Authors: Nicholas Andrade
Introduction: Allocation concealment, via randomization, blinding, and placebo control, is a crucial safeguard against bias in the evaluation of therapeutic effectiveness. Meta-epidemiologic studies confirm the importance of adequate concealment for accurate estimates of treatment effect. For invasive procedures, use of a sham control procedure is necessary for optimal allocation concealment, and allows separation of specific (physiological) from nonspecific (psychological) treatment effects.
Methods: We searched for all sham-controlled trials of invasive procedures and analyzed them by disease, procedure, specialty, publication date, citation frequency, and impact on clinical guidelines. Next we focused specifically on neurosurgery, and analyzed relevant sham-controlled trials with respect to date, subject matter, and trial result.
Results: Across medicine, the frequency of sham-controlled trials is increasing (pre-1980–3; 1980-89–18; 1990-99–41; 2000-09–95). Nearly all interventional specialties have seen the publication of at least one sham-controlled trial. Most sham-controlled trials have evaluated ìminimally invasiveî procedures directed at subjective or fluctuating outcomes. 21 sham-controlled trials of neurosurgical procedures have been published to date, all since 2000. Neurosurgical procedures studied in sham-controlled trials include shunting, various forms of neurostimulation, cell transplantation, and vertebroplasty.
Conclusions: Sham-controlled trial design is increasingly employed to evaluate invasive procedures, especially those aimed at improving subjective or fluctuating outcome measures. This is probably due to increasing recognition of the importance of allocation concealment and control for nonspecific (ìplaceboî) treatment effects. In some fields, eg interventional pain management, use of sham controls appears to be becoming a de facto standard, and neurosurgical trials are increasingly using sham controls as well. The distinction between specific and nonspecific treatment effects may help to maximize the benefit/risk ratio of therapeutic interventions.
Keywords: Evidence, placebo, sham, controlled trials
Objectives: Understand the history of surgical randomized controlled trials and sham controlled interventional trials. Understand current and future trends in surgical trials. Identify situations in which nonspecific treatment effects and sham controlled trial design should be considered.
Subject: Spine
Title: Spondylolysis and Isthmic Spondylolisthesis–Can They Be Considered Pathological?
Authors: Nicholas Andrade; Viktor Bartanusz
Introduction: Surgical treatment is widely applied in patients with low back pain (LBP) and spondylolysis (SL) or isthmic spondylolisthesis (IS), on the assumption that this imaging abnormality is the cause of the patient’s symptoms. However, given that back pain and asymptomatic imaging abnormalities are both ubiquitous, this assumption of causality should be tested rigorously prior to recommending surgical intervention. Statistical association is one of several generally accepted criteria to establish causation. Our goal was to assess the primary data supporting or contradicting the hypothesis that spondylolysis or isthmic spondylolisthesis is associated with low back pain.
Methods: We searched Pubmed using Title=isthmic spondylolisthesis OR spondylolysis. Papers were then reviewed by hand. Primary data papers were defined as either 1) a cross-sectional study of the association of either imaging finding and low back pain in the general population, or 2) a longitudinal study that compared the incidence of low back pain in subjects with or without spondylolysis or spondylolisthesis. We also reviewed the reference section of all primary data papers and review articles to identify any other articles that might have been missed in the primary search.
Results: We identified 19 primary data papers. Of 14 cross sectional reports evaluating the association of SL or IS with LBP, five found an association, two were inconclusive, and seven found no such association. Of four longitudinal studies comparing the incidence of LBP in subjects with and without SL or IS, only one found an association, and the other three found no difference in the incidence of LBP in subjects with SL or IS compared to those without.
Conclusions: Existing data do not support an association between SL or IS and LBP, casting doubt on claims of causality. An alternative explanation for the observed benefits of surgery noted in some trials is that they are entirely due to nonspecific treatment effects, as has been shown for other interventional procedures directed at the relief of pain.
Keywords: spondylolysis, isthmic spondylolisthesis, causality, back pain
Objectives: Understand the intellectual basis for ascribing patient symptoms to diagnostic findings. Be familiar with the epidemiologic data regarding the association of low back pain with spondylolysis and isthmic spondylolisthesis. Evaluate the empiric support for the hypothesis that spondylolysis and isthmic spondylolisthesis are causes of back pain.
Subject: Functional
Title: First North American case of Neuroferritinopathy with 16bp heterozygous duplication of the C terminus on the FTL gene
Authors: Chris Graham; Stuart Goodman
Introduction: Neuroferritinopathy is a rare, autosomal dominant, adult-onset movement disorder, associated with iron and ferritin deposition in the basal ganglia, secondary to mutations in the ferritin light chain gene (FTL).1 There are fewer than 100 reported cases worldwide. This is the first identification of a 16bp heterozygous duplication of the C terminus on the FTL gene in North America. Clinical, radiologic and genetic findings are presented.
Methods: Proband JF is a 42-year-old male of Dutch and Swedish ancestry who presented with a progressive history beginning in his late teens of diffuse dystonic posturing, choreathetoid movements, and ataxia. He also developed an orolingual dyskinesia evidenced by the absence of expressive speech, but he retained the ability to demonstrate comprehension by holding up 1 or 2 fingers for ìyesî or ìno.î His mother had similar progressive symptoms beginning in her early twenties that led to immobility and ultimately her death at age 34. JF had multiple neurologic work-ups resulting in various diagnoses, from progressive neurodegenerative process, to spastic quadraparesis, to progressive dystonia musculorum deformans. Treatments included physical therapy, Botox injections, and oral and intrathecal Baclofen, none of which provided more than minimal symptomatic relief. JF was referred to the neurosurgery service with a diagnosis of spasticity for replacement of his intrathecal Baclofen pump that had reached end-of-service. His clinical presentation however was more consistent with generalized dystonia, and he was considered for deep brain stimulator therapy. His preoperative MRI imaging revealed not only extensive volume loss with symmetrically enlarged sulci and ventricles, but also a striking complete cavitation of the basal ganglia, suggesting the possibility of a genetic metabolic disorder. His surgery was cancelled and a broader work up began, including repeat MRI with multiple acquisition sequences, metabolic blood tests, and genetic sequencing. Normal serum iron and ferritin levels were found. Gene sequencing of exon 4 of the ferritin light chain (FTL) gene revealed a 16bp heterozygous duplication (c.469_484dupGGCCCGGAGGCTGGGC).
Results: Discussion contained in paper
Conclusions: Hereditodegenerative disorders and secondary dystonias should be considered in the differential diagnosis in all cases of movement disorders. The possibility of encountering one of these rare disorders warrants ordering MR imaging in the work-up of Parkinsonism, Huntingtonís chorea, or dystonia. Clearly, further research into the distinguishing features of FTL mutations is important. Our understanding of the differences in clinical presentation, MRI findings, and penetrance may increase with the diagnoses of more FTL mutations.
Keywords: neuroferritinopathy, parkinsons, dystonia, cavitation
Objectives: 1. recognize basal ganglia cavitation as possible neuroferritinopathy 2. Avoid a potential pitfall in the work up of a patient for DBS 3. Understand neuroferritinopathy as a rare gentic disorder.
Subject: Tumor
Title: Prolactinomas, Psychosis and Management Strategies: Report of 2 Cases and Review of the Literature
Authors: Daniel R Klinger; Jeremy J. Lewis; Sam Barnett
Introduction: Prolactinomas are the most common pituitary tumors, and their first-line therapy involves treatment with dopamine agonists that carry a side effect of induced psychosis. Patients with psychotic disorders such as schizophrenia are typically treated with dopaminergic-receptor inhibitors which can elevate serum prolactin levels leading to symptomatic hyperprolactinemia. The treatment of prolactinomas in patients with psychotic disorders presents a unique challenge as therapy aimed at treating one pathology (prolactinoma) may worsen or complicate the treatment of the other (psychosis), and vice versa.
Methods: We present two cases of patients with known histories of paranoid schizophrenia who each presented with large, symptomatic prolactin-secreting macroadenomas. We subsequently reviewed the existing medical literature regarding the treatment of prolactinomas in the context of concurrent psychotic disorders.
Results: Patient A is a 37 year-old man with paranoid schizophrenia who presented in 2011 with psychiatric medication non-compliance and aggressive, erratic behavior. He was found to have significant visual field loss in all quadrants of the right eye and temporal field cut in the left eye as well as a prolactin level over 11K. Further workup revealed a giant, partially cystic prolactinoma. He was initially treated with cabergoline and aripiprazole. His tumor progressed at follow-up and he developed worsening vision in the right eye and mild left hemiparesis secondary to an expanded cystic component of the tumor compressing the right temporal lobe. He underwent a right frontal craniotomy with cyst decompression. Post-operatively his hemiparesis resolved but he developed a third nerve palsy. He is currently being treated by Neuro-oncology with temodar. Patient B is a 72 year-old man with paranoid schizophrenia who initially presented in 2004 with bilateral vision loss and a large prolactin-secreting macroadenoma. He underwent transsphenoidal resection with initial tumor control and improved vision. Subsequently, he had a psychotic episode requiring hospitalization. Further follow-up revealed tumor recurrence requiring CyberKnife radiosurgery and several years later repeat transsphenoidal resection after his vision deteriorated further. He currently has stable vision, mild stable hyprolactinemia and is being treated with aripiprazole by Psychiatry.
Conclusions: The treatment of prolactinomas in the setting of concurrent psychotic disorders presents an unusual clinical dilemma in that first-line medical therapy may worsen the patientís psychiatric disease. Early surgical intervention for large or symptomatic lesions may be the best strategy although establishing reliable clinical follow-up and preventing psychiatric decompensation are unique considerations in this patient subgroup. Coordinated care between neurosurgical, endocrine and psychiatric services is recommended.
Keywords: prolactinoma, psychosis, dopamine-receptor antagonists
Objectives: – to understand the causes and symptoms of hyperprolactinemia – to understand the possible sequela of dopamine-agonist treatment of prolactinomas in the setting of pre-existing psychotic disorders – to formulate neurosurgical treatment strategies in patients with prolactinomas and concurrent psychotic disorders
Subject: Tumor
Title: Tissue Biomarkers Of Hypoxia And Vascularity Taken From Specific Intratumoral Areas Correlate With Preoperative DSC And DCE MRI And Are Predictive Of Malignant Glioma Patient Outcome.
Authors: Randy L. Jensen; David L. Gillespie
Introduction: Measures of tumor vascularity and hypoxia have been correlated with glioma grade and outcome. Recently developed modeling methods for analysis of dynamic contrast-enhanced MRI (DCE-MRI) data have demonstrated the potential to noninvasively map a broad range of parameters potentially relevant to tumor hypoxia, blood flow, and vascularity. In this prospective observational cohort pilot study, we used preoperative imaging to correlate specific areas of glioma tissue? with molecular markers of hypoxia, tumor vascularity, and tumor proliferation along with progression free and overall patient survival.
Methods: A distributed parameter (Gamma Capillary Transit Time) model was used to generate maps of tumor blood flow (F), extraction fraction (E), permeability-surface area product (PS), transfer constant (Ktrans), washout rate (kep), interstitial volume (ve), blood volume (vb), capillary transit time (tc), and capillary heterogeneity (α(-1)) from pre-operative DCE-MRI data in human glioma patients. Multiple tissue samples were obtained from specific areas from each tumor with an MRI-guided intraoperative navigation system. These areas included peritumoral edema (PE, non-enhancing area surrounding tumor, bright on T2-weighted MRI), active tumor (AT, nodular enhancing tissue at the outer edge of tumor), hypoxic penumbra (HP, enhancing area immediately surrounding areas of necrosis), and necrotic core (NC, heterogeneous non-enhancing tumor core). Each of these areas was evaluated for the expression of hypoxia-regulated molecules including hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), carbonic anhydrase nine (CA-IX), and glucose transporter-1 (GLUT-1) as well as for tumor vascularity, and tumor proliferation (MIB-1 labeling index). Mean DCE-MRI parameter values were computed in regions of interest corresponding to tissue sample sites and marker expression compared with imaging results.
Results: Patient survival was found to correlate with DCE parameters in two cases: α(-1) in AT (p=0.005), and ve in areas of PE (p=0.020). Statistically significant correlations between several of the DCE parameters and tissue markers were also observed. Specifically: 1). vb is correlated with VEGF (R2=0.475, p=0.0092) and HIF-1 (R2=0.323, p=0.043) expression in AT, 2). tc is correlated with HIF-1 in AT (R2=0.527, p=0.005), HP (R2=0.761, p=0.023), and PE (R2=0.696, p=0.0052), and with VEGF in AT (R2=0.346, p=0.034) and HP (R2=0.793, p=0.0173), 3). α(-1) is correlated with VEGF in AT (R2=0.442, p=0.013) and PE (R2=0.951, p<0.0001), and 4). kep is correlated with VEGF in PE (R2=0.579, p=0.0065) and NC (R2=0.868, p=0.0069). In addition, MIB-1 index is correlated with VEGF expression in HP (R2=0.7933, p=0.0071) and PE (R2=0.4546, p=0.033), and HIF-1 and VEGF expression are correlated in all tumor areas.
Conclusions: Our pilot study findings suggest that with further work it may be possible to use DCE-MRI to make noninvasive preoperative predictions of areas of tumor with increased hypoxia and proliferation. This has the potential to both make unprecedented prognostic decisions and to guide therapies to specific tumor areas.
Keywords: perfusion MRI, hypoxia, microenvironment,
Objectives: 1. Recognize the potential for perfusion MRI to predict intratumoral microenvironment 2. Understand the role of tissue biomarker discovery and patient outcome 3. Discuss the correlation of tissue biomarker information and DCE-MRI parameters
Subject: Tumor
Title: Development Of An Animal Model Of Post-Treatment Pseudoprogression.
Authors: Randy L. Jensen; David L. Gillespie
Introduction: The lack of a definitive imaging modality to distinguish post-treatment radiographic imaging changes (PTRIC), including pseudoprogression and radiation necrosis, from true tumor progression presents a major unmet clinical need in the management of GBM patients. At present there are no animal models of PTRIC
Methods: We developed a rodent model of PTRIC by intracranially implanting rats with either preirradiated (2-10 Gy) or nonirradiated glioma cells transfected with a constitutively active luciferase reporter. The rats were treated with or without temozolomide (TMZ) chemotherapy and rats implanted with nonirradiated cells were treated with focused tumor irradiation (2-10 Gy) to the implanted tumor cells and surrounding brain. Cell growth was monitored by bioluminescence imaging of the luciferase reporter and brain MRI measurement of tumor growth. Tumor histology was confirmed by light microscopy and immunohistochemistry.
Results: Animals implanted with irradiated cells did not produce PTRIC even when co-treated with TMZ. Rats considered to have tumor progression demonstrated steadily increasing luciferase activity coupled with increasing gadolinium-enhanced tumor volume and were found in animals receiving radiation doses less than 2Gy X3 without TMZ chemotherapy. Conversely, pseudoprogression was manifest by decreasing luciferase activity with increasing gadolinium volume over time found in tumors treated with 2Gy X3 and concurrent TMZ. Tumor histology was correlated with luciferase activity.
Conclusions: Our preliminary data suggests a potential model of pseudoprogression and/or radiation necrosis. This model needs to be further characterized with advanced imaging techniques including perfusion MR and multitracer PET imaging. We plan to use this model for future molecular and cellular studies to understand the cause and potential exploitation of these effects for better patient care.
Keywords: Pseudoprogresssion, imaging, rodent, enhancement
Objectives: 1. Understand the clinical problem of pseudo progression 2. Describe a rodent model that can mimic this unique clinical situation. 3. Discuss potential imaging methods to differentiate pseudoprogression and true tumor progession
Subject: Tumor
Title: Magnetic resonance FLAIR and T2 tumor volumes obtained intraoperatively compared to post-operative volumes in high and low grade gliomas
Authors: Randy L. Jensen; Walavan Sivakumar; Karen L Salzman; Forrester Lensing
Introduction: Intraoperative MRI is a useful tool in the operative management of human gliomas. In non-contrast enhancing gliomas, and to a lesser extent enhancing tumors, the T2 and FLAIR signals are important targets to determine target volumes for resection margins. We hypothesized that intraoperatively obtained MRI T2 and FLAIR signal volumes might not reflect corresponding post-operative volumes due to tumor edema after resection and brain manipulation.
Methods: We examined 12 low-grade gliomas (LGG, 9 low-grade astrocytomas and 3 oligodendrogliomas) and compared them to 13 high-grade tumors (HGG, 4 anaplastic astrocytomas, 3 anaplastic oligodendrogliomas, and 5 glioblastomas). Volumetric assessment of T2 and FLAIR signals were performed using the OSRIX image analysis program and ratios calculated for preoperative, intraoperative, and post-operative MRI images for each patient.
Results: Not surprisingly, for both LGG and HGG intraoperative and postoperative FLAIR and T2 signal volumes were significantly lower than post-operative volumes. Interestingly, for LLG the ratio of intraoperative FLAIR volume was on average 249% higher than postoperative FLAIR volume (range of 11-982%) and intraoperative T2 volume was 56% (range 0-149%). of postoperative T2 signal volume. For HGG, the ratio of intraoperative FLAIR volume was on average 255% higher than postoperative FLAIR volume (range of 19-1432%). Intraoperative T2 volume was 79% (range 27-168%) of postoperative T2 signal volume. When all tumor grades are analyzed together similar trends are found.
Conclusions: Postoperative FLAIR signal volumes are significantly lower and T2 signal volumes significantly higher than intraoperatively obtained corresponding volumes for LGG. HGGs demonstrated a similar trend for FLAIR signal volumes while T2 signal volume was similar for both intraop and post-op images.
Keywords: Glioma, Magnetic resonance imaging, Intraoperative, Tumor
Objectives: Understand the increasing use of the intraoperative MRI Understand the increased utilization of different imaging modalities in intraoperative MRI Appreciate the difference between intraoperative and postoperative imaging findings with the intraoperative MRI
Subject: Socioeconomic
Title:
Authors: Howard MD Morgan
Introduction: The curbside consult is a long-standing part of the practice of medicine. What does and does not constitute a curbside conslut is not always clear in practice, and court decisions seemingly have placed the practice in jeopardy.
Methods: The medical literature was searched regarding what constitutes and does not constitute a curbside consult. Some recent court decisions were reviewed.
Results: Recommendations for reducing the risks of the curbside constult are made.
Conclusions: Curbside consultation will likely continue in the practice of medicine in general and neurosurgery in particular. A few simple rules will held reduce the risks of this practice.
Keywords: Curbside consult, informal consult, medical ethics
Objectives: Recognize what constitutes a curbisde consult. Realize some of the practical, ethical and legal risks of curbside consultation. Recognize how to avoid these risks.
Subject: Cerebrovascular
Title: Cortical Spreading Depression (CSD) in a CCM (Cerebral Cavernous Malformation) Mouse Model
Authors: Khaled M Krisht; KC Brennan; Kevin Whitehead
Introduction: Inducible knockout (KO) of the 3 cerebral cavernous malformation (CCM) genes, Krit-1, CCM2 and Pdcd10 has been used to study the functional and structural endothelial cell aberrations associated with CCM and to help elucidate the molecular mechanisms involved in lesion formation in a murine model. Recent studies on middle cerebral artery vessels from Krit-1 and CCM2 KO mice demonstrated a deficiency in endothelial-dependent vasodilation that can be rescued with the superoxide scavenger, Tempol. To date there has been no in-vivo investigation into the neurovascular behavior in CCM knockout mice with cortical and subcortical vascular lesions. Our study evaluates neurovascular coupling in CCM mice using optical intrinsic signaling (OIS) to study cerebral blood volume responses to direct visual and sensory stimulation and to study cortical spreading depression (CSD) induced with increasing concentrations of KCl.
Methods: KO mice induced between postnatal days 1-7 as well as their non-induced control litter mates were subject to a controlled experimental design utilizing optical intrinsic signal imaging of the fronto-parieto-occipital cortex to evaluate for sensory responses to visual and hindpaw stimulation as well as KCl-induced CSD (see figure).
Results: 83.3 % of KO mice had a second CSD versus 20 % of control mice. CSD in KO mice seems to be more often facilitated (4/6 vs 0/5) by sensory input and has a lower propagation velocity compared to control.
Conclusions: A mutation in any one of the 3 CCM genes leads to dysfunctional endothelial cells, which perturbs normal endothelial dependent vascular response. Cortical spreading depression, a well-conserved phenomenon involving neurovascular coupling appears to be different in CCM KO mice versus control mice. KO mice are more likely to have multiple CSDs that are more often facilitated by sensory input with a lower propagation velocity. This may have important clinical and therapeutic implications.
Keywords: CCM, CSD, Optical Intrinsic Signaling (OIS), Endothelial
Objectives: Gain a conceptual understanding of cortical spreading depression including associated changes in K and field potential voltage. Understand associated cerebral blood volume changes that accompany cortical spreading depression. Learn the usefulness of OIS in detecting regional blood volume changes in response to stimulation (maps) Understand the different findings of CSD characteristics between KO and Control mice Understand the possible clinical and therapeutic implications of our early findings
Subject: Tumor
Title: Fusiform Dilatation of the Cavernous Carotid Artery in Acromegalic Patients
Authors: Walavan Sivakumar; William Couldwell; Jay Riva-Cambrin; Karen L Salzman; Roukoz Chamoun
Introduction: Surgeons undertaking transsphenoidal surgery in patients with acromegaly confront multiple unique challenges secondary to the anatomic alterations caused by growth hormoneñsecreting tumors. The senior author has noted a fusiform dilatation to the cavernous carotid artery in many acromegalic patients. The authors aim to quantify this dilatation and correlate it with potential contributing factors.
Methods: Clinical and radiographic data were retrospectively assessed in acromegalic patients undergoing transsphenoidal surgery from 2000 through 2011. Randomly selected patients with nonsecreting pituitary adenomas were used as the control cohort. Demographic information, comorbidities, and preoperative growth hormone and insulin-like growth factor-1 levels were recorded. Magnetic resonance (MR) imaging variables included tumor size, diameters of the petrous, cavernous, and supraclinoid segments of the carotid artery and extent and location of cavernous sinus invasion. Independent correlations between acromegaly and each variable were assessed with multivariate regression analysis.
Results: Forty randomly selected patients with growth hormoneñsecreting adenomas who underwent surgery and had MR imaging with thin coronal slices of the pituitary region were enlisted in our study cohort. The mean age was 45.7 years. Forty-two males (52.5%) were included in the study. Mean carotid artery diameter measurements for acromegalic and control patients, respectively, were 4.2 vs. 3.8 mm (petrous carotid), 5.0 vs. 4.0 mm (cavernous carotid), and 3.3 vs. 2.9 mm (supraclinoid carotid). Multivariate analysis showed only age and cavernous carotid diameter were statistically significant independent variables (p = 0.02, p < 0.001, respectively). Age, tumor size, growth-hormone or insulin-like growth factor-1 levels, and cavernous sinus invasion did not correlate with cavernous carotid artery diameter.
Conclusions: In patients with acromegaly, there is a fusiform dilatation of the cavernous carotid artery that must be considered when planning transsphenoidal surgery.
Keywords: pituitary adenoma, acromegaly, growth hormone, transsphenoidal surgery
Objectives: Understand the reason for increased surgical risk for transsphenoidal surgery in growth hormone secreting pituitary adenoma patients compared to those with other pituitary adenomas. Understand the different intracranial vascular anatomy in patients with acromegaly. Be able to evaluate for fusiform dilatation of the cavernous carotid artery using coronal thin-cut magnetic resonance imaging.
Subject: Spine
Title: Laminoplasty for Spinal Tumors a Twenty Five Year Experience
Authors: Albert H. Capanna; Dawn M. Capanna
Introduction: Laminoplasty for Spinal Tumors a Twenty Five Year Experience
Methods: The use of laminoplasty when removing spinal tumors greatly improves healing. Epidural, intradural and intramedullary tumors are removed and the spinal reconstruction aids in healing and decreases post-operative scar formation. Pediatric patients do particularly well at healing the laminar openings. All patient age groups do not develop the sometimes seen scalloping in their spine post complete laminectomy.
Results: The laminae and spinous processes are removed en-bloc regardless of how many segments are removed. This is accomplished through small laminotomies at the superior and inferior laminae and then using a craniatome with dura guard to cut along the laminae on both sides of the spinal canal. The bones are the removed en-bloc.
Conclusions: After removal of the tumor and pia-arachnoidoplasty and duraplasty are completed, the laminae are brought back into position. Originally, the laminae were sutured together at each level with nylon sutures. Instrumentation with plates and screws are now available. There were no complications secondary to the procedure and no hematoma formation or remote take backs to surgery.
Keywords: Laminoplasty, Spine, Tumor
Objectives: 1. Know how to perform a laminoplasty. 2. Know the various indications for laminoplasty. 3. Understand the benefit of laminoplasty vs. laminectomy.
Subject: Tumor
Title: Fractionated Stereotactic Radiosurgery is Efficacious and Well-tolerated in Pediatric Intracranial Neoplasms
Authors: Todd C. Hankinson; S. Reed Plimpton; Nicholas K. Foreman; Michael H. Handler; Arthur K. Liu
Introduction: While data in the adult population indicates that fractionated stereotactic radiosurgery (fSRS) is associated with high degrees of efficacy and tolerability, there is little published experience dedicated to the treatment of children using fSRS.
Methods: We retrospectively reviewed the experience at Childrenís Hospital Colorado/University of Colorado Denver in treating 24 lesions in 15 pediatric patients (age 2.6-24.9y, median 10.0y) using fSRS between 2007-2012.
Results: Patients received a median of 24Gy (range 20-25Gy) in 3 fractions (range 3-5). Two patients, one with a multiply recurrent astroblastoma and one with an Ewingís Sarcoma metastasis, had not received previous radiation therapy. Twenty-three lesions (95.8%) were WHO Grade III-IV, with the exception being a pilomyxoid astrocytoma. Median tumor volume was 2.7 cc (0.4-94.5 cc). Median follow-up was 12.5 months (range 1.0-47.1 months). The local control rate was 91% at 2 years and overall survival was 76% at 2 years post-fSRS. Radiation necrosis was seen at 7 of the treated sites (29.2%) with a median onset time of 4.1 months (range 1.4-8.4 months).
Conclusions: fSRS is an effective and well-tolerated treatment for multiple types of intracranial pediatric neoplasms. Radiation necrosis may be more common than in the adult population.
Keywords: Stereotactic Radiosurgery, Pediatric Brain Tumor, Radiation Necrosis
Objectives: 1. Discuss the definition of fractionated sterotactic radiosurgery 2. Discuss the role of fractionated stereotactic radiosurgery in pediatric neuro-oncology 3. Understand some differences in the use of fractionated stereotactic radiosurgery in the pediatric and adult populations
Subject: Socioeconomic
Title: Platelet Aggregometry Results after the Use of Common Non-Steroidal Anti-inflammatory Medications: Evaluation for the Perioperative Setting
Authors: William W. Scott
Introduction: Because of the concern for possible bleeding related with the use of NSAID medications, it has been common practice to postpone certain invasive procedures, withhold these medications after surgery, or in some emergent instances administer expensive treatments (i.e. administration of platelets, DDAVP). There is a paucity of data in the neurosurgical literature on the effects of NSAID medications on platelet function, and guidelines for perioperative surgical planning are needed. To provide further understanding of platelet function for the surgical setting, 5 commonly used NSAIDs were studied through whole blood platelet aggregometry (WBPA).
Methods: In addition to ASA, two COX-1 medications (naproxen and ibuprofen) and 2 COX-2 medications (celecoxib and meloxicam) were analyzed in healthy males and females between the ages of 20 to 55. Each individual initially underwent a baseline WBPA study, and then took the recommended daily dosage of a particular medication for 3 days with subsequent WBPA testing until aggregation normalized. Results were interpreted as the medication “having effectî on platelet aggregation if the WBPA agonist values were less than or equal to 4 ohms.
Results: Twelve individuals with normal baseline platelet functions on initial or subsequent WBPA testing were enrolled, including 6 males and 6 females (mean ages 42 and 40 years). The COX-2 inhibitor meloxicam had no effect against platelet aggregation at 24 hours in either males or females. At 24 hours, the COX-2 inhibitor celecoxib had no effect against platelet aggregation in females, and no effect in 67% of males. In the celecoxib group, differences against arachidonic acid, collagen and ADP levels at 24 hours between genders was found to be statistically significant (p=0.001, p=0.047 and p=0.039, respectively). The COX-1 inhibitor ibuprofen had no effect against platelet aggregation at 24 hours in females, and no effect in 83% of males at 24 hours. In the ibuprofen group, differences against arachidonic acid, collagen and ADP at 24 hours between genders was found to be statistically significant (p=0.045, p=0.007, and p=0.023, respectively). The COX-1 inhibitor naproxen had no effect against platelet aggregation in 83% of females at 48 hours, no effect in 50% in males at 48 hours, and no effect against platelet aggregation at 72 hours in either males or females. When comparing the naproxen group against ASA results,there were no statistically significant differences at 24 hours against arachidonic acid or ADP(p=0.338 and p=0.486, respectively).
Conclusions: Variations from baseline platelet aggregometry values can occur in individuals taking NSAID medications; however, in individuals who are otherwise healthy and take no additional dietary supplements, these variations are short-lived and are not necessarily physiologically relatable to platelet aggregation function. This data suggests, as it relates to the above medications and perhaps to a wider variety of COX-1 and COX-2 inhibitor medicaitons, that surgery is probably safe at a time interval between 24 and 72 hours, depending on type of medication and gender of the patient.
Keywords: Non-steroidal anti-inflammatory medications, Whole Bloood Platelet Aggregometry
Objectives: 1)Understanding of whole blood platelet aggregometry. 2)Relate NSAID medications to WBPA results. 3)Surgical safety relating WBPA reuslts and NSAID medicaiton use.
Subject: Trauma
Title: Non-Transfer Protocol for Mild Traumatic Brain Injury with Small Intracranial Hemorrhage in a Rural Hospital Setting
Authors: Andrew S Levy; Allesandro Orlando; Kristin Salottolo; David Bar-Or
Introduction: Recent literature examining mild traumatic brain injury (mTBI) with small intracranial hemorrhage (ICH) has suggested that the neurosurgical intervention rate is between 0% and 3%, and that these injuries do not always necessitate a transfer to a higher-level trauma center with neurosurgical capabilities.
Methods: In 2007, a non-transfer protocol was implemented at a rural Level III Trauma Center in the mountains of Colorado. Adult patients with mTBI (GCS 13-15), CT showing small ICH, and no coagulopathy were included in the protocol. CT scans were reviewed by the on-call neurosurgeon at an affiliated Level I Trauma Center, and consensus was obtained on the suitability for non-transfer. Early and long-term outcomes were evaluated using a trauma registry and telephone interviews.
Results: A total of 57 patients met the criteria to stay at the rural Level III Trauma Center. The median hospital LOS was one day (IQR=1d). No patient required a neurosurgical intervention or post-admission transfer to a Level I facility. No patients deteriorated after admission, there were no in-hospital deaths, and all patients were discharged home. There were no re-admissions or late complications that we could identify.
Conclusions: There is a sub-population of mTBI patients with small ICH that do not require transfer to a higher level Trauma Center with neurosurgical capability. A non-transfer protocol for mTBI patients with small ICH can lead to a more efficient use of hospital resources while providing safe, effective and economical healthcare.
Keywords: Traumatic Brain Injury, Subarachnoid Hemorrhage, Transfer Protocol, Rural Hospital
Objectives: Identify a subset of patients with mild TBI and small intracranial hemorrhage that do not require transfer to a trauma center with neurosurgical capability. Understand the criteria for safely selecting this subset of patients. Understand the benefits of developing a non-transfer protocol for rural hospitals without neursurgical capabilities, to select and manage patients with mild TBI and small ICH, in order to optimize safety, efficiency and resource utilization in the care of this subset of patients.
Subject: Trauma
Title: Breach of Posterior Wall of the Frontal Sinus: Management Without Cranialization
Authors: Ken R Winston; Jacob L Freeman
Introduction: Cranialization is a frequently practiced surgical intervention in the management of fractures of the posterior wall of the frontal sinus, especially those that are displaced, comminuted or associated with CSF leak. While this procedure has been shown to decrease the risk of subsequent intracranial infection it is not always effective and carries with it its own set of risks. It is therefore both reasonable and important to examine the efficacy and complication rate of fracture management without cranialization.
Methods: The authors conducted a retrospective analysis of prospectively accrued data from 1998 to 2013 on 34 patients with posterior wall frontal sinus fractures that were managed without cranialization. Hospital charts and CT scans were reviewed in detail to assess specifics of each injury, operative details, and the most common post-operative outcomes associated with posterior wall fractures including CSF leak, intracranial infection (meningitis, abscess) and mucocele.
Results: 33 of the 34 patients are currently alive. Five patients (14.7%) developed a new CSF leak. Four of these were successfully stopped with CSF diversion (lumbar drain or ventriculostomy) and one stopped on its own. None of these patients developed subsequent intracranial infection or required conversion to a permanent shunt. One patient (3%) had persistent CSF leak despite initial diversion and surgery. This patient required reoperation to stop the leak. One patient (3%) developed new post-operative intracranial infection and another suffered from persistent meningitis that was present prior to first operation. None of the patients in this series had developed a mucocele by the time of their last follow-up. Neither degree of posterior wall displacement nor presence of nasofrontal duct obstruction predicted higher complication rates. We report one complication associated with iatrogenic breech of the posterior wall of the frontal sinus. This was a new CSF leak which was quickly stopped with CSF diversion. Follow-up times ranged from 2 days to 6 years with a median follow-up time of 1 month. Overall, new/early complications were found in five of the 34 patients (14.7%) in this series however only one (3%) of these was of any real detriment to the patient. There were no late complications (>6 months).
Conclusions: The results of this investigation support the position that management of posterior wall fractures without cranialization is safe and well tolerated. Complication rates are similar to those of patients who undergo cranialization. Furthermore, the majority of the complications following our management strategy were CSF leaks that were easily stopped with CSF diversion and did not result in subsequent intracranial infection. Therefore, cranialization should not be performed in the majority of patients with fractures of the posterior wall of the frontal sinus.
Keywords: Cranialization of Frontal Sinus, CSF Rhinorrhea, Frontal Sinus Fracture, Frontal Sinusitis
Objectives: 1. Better understand the surgical management strategies that exist today for treatment of frontal sinus fractures. 2. Recall the most common complications (short and long term) associated with these fractures. 3. Understand that most patients with posterior wall frontal sinus fractures have similar post operative complications and complication rates following cranialization versus a more conservative management of their fracture.
Subject: Trauma
Title: Pharmacologic Thromboprophylaxis in Patients with Traumatic Brain Injury
Authors: Andrew S Levy; Kristin Salottolo; Patrick Offner; Charles Mains; David Bar-Or
Introduction: Patients with Traumatic Brain Injury (TBI) may be at increased risk for venous thrombo-embolism (VTE), but routine Pharmacologic Thromboprophylaxis (PTP) with agents such as Lovenox or subcutaneous Heparin may result in an increased risk of intracranial hemorrhage (ICH) progression in a subset of patients with TBI and ICH. There is very little evidence regarding the risks and benefits of PTP in patients with hemorrhagic TBI.
Methods: We retrospectively reviewed patients with blunt TBI and ICH who were admitted to our Level I trauma center. In order to assess the efficacy of PTP use in patients with TBI, PTP use was analyzed as an independent risk factor for VTE using separate logistic regression models for each definition of PTP use: (1) administration of PTP; (2) timing of PTP early [<72 hours] vs. late [>72 hours]); and (3) continuous versus interrupted use of PTP. In order to assess progression of hemorrhage we analyzed the patients in two groups: patients with a stable initial follow-up (F/U) computed tomography (CT) and patients with hemorrhage progression on initial F/U CT. Risk factors potentially associated with hemorrhage progression were analyzed using logistic regression.
Results: Four hundred eighty patients with TBI were identified for the study. VTE occurred in 15 patients (3.13%). VTE developed in six patients despite early PTP (5.56%), four patients with late PTP (2.72%), and five with no PTP (2.22%). Neither administration of PTP nor timing of PTP was an independent predictor of developing a VTE (PTP vs. none: odds ratio [OR] = 0.36, p = 0.18; early PTP vs. late PTP: OR = 2.00, p = 0.41). PTP was administered continuously in 188 patients (73.7%). Patients with interrupted PTP had a significant increased odds of developing VTE compared with patients with continuous PTP (OR = 7.07, p = 0.04). Walking before discharge significantly decreased the odds of developing a VTE (OR = 0.19, p = 0.02). In patients with ICH progression on initial F/U CT, predictors of subsequent hemorrhage progression included exposure to PTP (odds ratio [OR]: 13.07, p = 0.01), extradural/subdural hemorrhage (OR: 5.15, p = 0.03), Glasgow Coma Score 3ñ8 (OR: 4.64, p = 0.03), and body mass index >25 (OR = 4.32, p = 0.03). PTP was not significantly associated with hemorrhage progression in patients with a stable initial F/U CT.
Conclusions: The administration of PTP in patients with TBI was not associated with decreased risk of VTE, even when given early or without interruption. Interrupted administration of PTP, on the other hand, was associated with significantly increased risk of VTE. Furthermore, PTP use was associated with a 13-fold increased odds of further hemorrhage progression in patients whose F/U CT within 1 day of admission showed ICH progression. PTP may be safe in a subgroup of patients with TBI and no ICH progression on initial F/U CT, but we have not been able to demonstrate that it reduces the risk of VTE in this population.
Keywords: Traumatic Brain Injury, Pharmacologic Thromboprophylaxis, DVT/PE, Lovenox
Objectives: Understand the risks of hemorrhage progression following PTP administration in patients with TBI. Understand the increased risk of VTE when PTP is interrupted in patients with TBI. Understand reasonable options for VTE prophylaxis in patients with hemorrhagic TBI.
Subject: Spine
Title: Medical Marijuana use characteristics in patients with chronic spine pain disorders
Authors: Michael A Finn; Chris Cain; Evaline Burger; Emily Lindley; vikas patel; devin RAZAVI-SHEARER; sarah henry
Introduction: The use of marijuana, or cannabinoids, as a pharmacologic treatment option for chronic pain syndromes has recently become a topic of great medical and social interest. In the state of Colorado, marijuana was legalized for medical purposes in 2000 and there are currently more than 115,000 patients registered to receive marijuana from over 800 dispensaries. More than 900 applications for medical marijuana cards are received by the state every day. In the last decade, research examining the role of cannabinoids in pain signaling pathways has begun to increase dramatically. However, there have been fewer clinical studies on the efficacy of cannabinoids for pain control or on the use characteristics of specific patient populations.
Methods: All adult patients presenting for initial evaluation at our institution were offered study enrollment. After informed consent, a brief survey regarding marijuana use was administered.
Results: Of the 200 patients offered enrollment, 184 (92%) agreed to participate. The sample consisted of 83 males (45%) and 101 females (55%). Of the 184 participants, 35 patients (19%) reported marijuana use for pain, most commonly via inhalation of smoked plant material (90%), followed by oral ingestion (45%), and inhalation of vaporized plant material (29%). While 31 of these patients (89%) used marijuana only for medical purposes, 4 patients (11%) also used marijuana recreationally. Marijuana users were significantly younger than non-users (44 vs. 54, p<0.05), but had similar educational and employment characteristics. There was a tendency towards a higher rate of usage in Hispanic patients (28.6%) than in White or African-American patients (18.4% and 12.5% respectively), but this difference did not reach statistical significance. Of the patients who reported marijuana use for their pain, 45.5% had a prescription, and 73% of these prescriptions were for spine pain. The majority of patients using marijuana (83%) also took other pain medications, primarily narcotics. Eighty-nine percent of users reported that marijuana ìgreatlyî or ìmoderatelyî relieved their pain and eighty-one percent felt that marijuana worked better than or equal to narcotics. Patients typically used marijuana less than 1-2 times a day, and 14% reported negative side effects of marijuana use, including depressed mood (5.7%), difficulty concentrating (20%), memory problems (8.6%), weight gain (25.7%), and paranoia (11.4%). Forty-three percent of these patients felt the negative side effects were significant.
Conclusions: Marijuana use for pain control is surprisingly frequent in our spine patient population. However, less than half of all users in our survey had a legal prescription for medical marijuana use. While marijuana users were younger than non-users, other demographic factors surveyed were comparable. Most patients using marijuana for their spine pain reported moderate to great alleviation of painful symptoms with tolerable side effects. However, negative side effects were reported. Further research is needed to ascertain whether marijuana use for chronic pain is truly efficacious in this population and to determine whether it has any effects on surgical outcomes.
Keywords: Medical Marijuana, Chronic Pain, Spine Pain
Objectives: Describe the frequency of medical marijuana use in a tertiary care spine population Describe the most common routes of delivery of medical marijuana Describe the most common side effects of medical marijuana use in the spine population
Subject: Functional
Title: Analysis of direct stimulation of primate visual cortex over 2 years
Authors: Tyler Davis; Paul A. House; Bradley Greger
Introduction: It has been hypothesized that a vision prosthesis capable of evoking useful visual perceptions can be based upon electrically stimulating the primary visual cortex (V1) of a blind human subject via penetrating microelectrode arrays.
Methods: As a continuation of earlier work, we examined several spatial and temporal characteristics of microstimulation using an array of 100 penetrating microelectrodes chronically implanted in V1 of a behaving macaque monkey. The principal finding was that two years after implantation we were able to evoke behavioural responses to electric stimulation across the spatial extent of the array using groups of contiguous electrodes.
Results: Consistent responses to stimulation were evoked at an average threshold current per electrode of 204 ± 49 µA (mean ± std) for groups of four electrodes and 91 ± 25 µA for groups of nine electrodes. Saccades to electrically-evoked targets using groups of nine electrodes showed that the animal could discriminate spatially distinct percepts with groups having an average separation of 1.6 ± 0.3 mm (mean ± std) in cortex and 1.0 ± 0.2 degrees in visual space.
Conclusions: These results demonstrate chronic perceptual functionality and provide evidence for the feasibility of a cortically-based vision prosthesis for the blind using penetrating microelectrodes.
Keywords: vision, stimulation
Objectives: …discuss barriers to the use of penetrating electrode arrays …note that chronic stimulation did not seem to cause functional harm to visual cortex. …discuss strategies for producing artificial vision
Subject: Trauma
Title: Case Report: Mal de Debarquement, an unusual condition following boat travel
Authors: John B Dietze
Introduction: Mal de Debarquement is a condition which consists of a lingering perception of movement which occurs following travel,usually by boat.
Methods: A 61 year old healthy female presented with a 2 1/2 year history of a persistent sensation of rocking movement after disembarking from a Mediterranean cruise. She was referred for neurosurgical consultation due to the identification of diffuse dural enhancement on MRI.
Results: Serial imaging revealed progression of dural enhancement and thickening ultimately resulting in biopsy. Biopsy revealed a resolving subdural hematoma. The patients symptoms have remained unchanged.
Conclusions: The pathophysiology of Mal de Debarquement remains elusive. It is a condition not likely to be encountered in neurosurgical practice, however should be considered when evaluating patients with similar history and symptoms when other etiologies are ruled out.
Keywords: Mal de Debarquement, dural enhancement, visual motion intolerance
Objectives: 1. Be familiar with the history and symptoms consistent with Mal de Debarquement. 2. Be aware of the natural history and prognosis of this condition. 3. Be familiar with the differential diagnosis for this condition.
Subject: Trauma
Title: Radiographic Assessment of Sub-acute Subdural Hematomas
Authors: Joel D. MacDonald; Sarah T Garber
Introduction: Treatment of sub-acute subdural hematoma remains a challenge in neurosurgery. Often, subdural hematomas arise in elderly patients with multiple medical comorbidities who may not be optimal surgical candidates. Several prior studies have examined the effectiveness of bedside twist drill craniostomy in this patient population for treatment of subdural hematoma versus operative evacuation under general anesthesia. These studies have shown equivalency in terms of recovery of neurologic function and date of discharge from the hospital. However, to date no study has examined radiological factors that may predict whether or not a patient with a subacute subdural hematoma could benefit from a bedside twist drill evacuation in lieu of an operative procedure.
Methods: The goal of our study was to analyze radiographic characteristics of operative subdural hematomas to try and determine predictive factors that would lead to successful evacuation via a bedside twist drill procedure. These radiographic factors included chronicity of subdural blood (acute, subacute, chronic), size of the hematoma, shape, Hounsfield units (density), presence of septations, midline shift, ventricular/sulcal effacement, and presence of thrombosed cortical veins if a study performed with contrast was available. We retrospectively examined the records of 104 patients treated for symptomatic subdural hematoma either via bedside twist drill or in the operating room between January 1, 2008 and December 31, 2011.
Results: Among these 104 patients, 21 patients underwent bedside twist drill craniostomy and 83 patients underwent operative evacuation. A total of 11 patients required a repeat intervention following their initial procedure, 2 in the bedside twist drill group and 9 in the operative intervention group. Presence of sulcal and/or ventricular effacement as well as midline shift were not found to be statistically significant in terms of outcome following intervention, while size > 12 mm and hyperdense hematomas (Hounsfield units > 30) favored operative intervention.
Conclusions: In conclusion, bedside twist drill craniostomy is an effective option in patients with smaller subacute hematomas who may not be optimal surgical candidates.
Keywords: Subdural hematoma; Chronic subdural hematoma; Twist drill; Burr hole
Objectives: Participants will be able to discuss the radiographic features of subacute subdural hematomas Participants will be able to discuss the indications for less invasive treatment of sub-acute subdural hematoma. Participants will be able to discuss the anticipated outcome for burr hole or twist drill drainage of sub-acute subdural hematoma
Subject: Trauma
Title: Concussion in Sports Injuries – The Return to Play Question
Authors: John B Dietze
Introduction: Recent events within organized sports have brought the issue of concussion into the limelight. Much of this attention is due to controversy that has arisen regarding the long term impact of multiple concussions occurring throughout the careers of professional athletes.
Methods: A survey of current literature is performed with emphasis placed on identifying specific evaluation criteria which will hopefully allow neurosurgeons to establish guidelines providing a more consistent means of making decisions about an athlete’s ability to return to play.
Results: The issue of sports related concussion has come to the forefront of public scrutiny in light of several recent high profile tragedies involving former professional athletes with histories of multiple concussions. Furthermore there is a growing body of evidence which suggests that a plurality of even mild injuries can result profound and devastating long term functional disabilities. As neurosurgeons we are called to task in an effort to set standards for our non-neurosurgical colleges who are on the sidelines or in the locker rooms to follow in their decisions of whether or not to allow athletes to return to the field of play.
Conclusions: In light of the significant role that sports plays in our culture, we are faced with competing agendas. There are often considerable ramifications behind benching an injured athlete, frequently resulting in pressure from coaches, front offices and players themselves to overlook injuries. Because of the reliance on the athlete to honestly and accurately report symptoms, which are often vague and highly subjective, there is great need for a reliable, and structured system to evaluate athletes with suspected concussions.
Keywords: Concussion, Contact Sports, Return to Play
Objectives: Be alert to the need to be objective in evaluating sports participants with suspected concussions. Be aware of the potential long term ramifications of multiple concussions. Identify criteria which will be helpful in developing a comprehensive and reliable system for evaluating athletes with concussions.