Is there bias in the treatment of degenerative spine disease? Analysis of anonymous voting via a multidisciplinary conference.

Many institutions have developed shared decision-making conferences as a mechanism for reducing treatment costs and improving patient outcomes. Little is known about the process of shared decision-making that takes place in these conferences, and there is the possibility of bias among surgeons and nonsurgeons for treatment within their respective specialties. This study was conducted to determine who is contributing to the decision-making process in a multidisciplinary spine conference and to what extent treatment biases exist among the surgical and nonsurgical members of this conference. Voting data were collected during weekly multidisciplinary spine conferences. Descriptive statistics were calculated on the cases presented and the number and type of physicians voting for each case. The likelihood of a particular vote in the surgeon and nonsurgeon cohorts was evaluated using relative risk calculation and multinomial logistic regression. A total of 262 consecutive cases were analyzed. No significant differences in treatment recommendation were observed between surgery and nonsurgical management (relative risk, 1.1; 95% CI, 0.97-1.25) when comparing votes from the surgeon and nonsurgeon cohorts. Multinomial logistic regression showed the odds of nonsurgeons recommending nonsurgical management over surgery was 20% greater than receiving that recommendation from their surgeon colleagues. Individual surgeon and nonsurgeon voters were evenly distributed above and below the mean for treatment recommendation. Individual and group biases exist among surgeons and nonsurgeons treating degenerative spine diseases. Multidisciplinary conferences may or may not level these biases, depending on how they are conducted.

Dural arteriovenous fistula-induced thalamic dementia: report of 4 cases.

Nonhemorrhagic neurological deficits are underrecognized symptoms of intracranial dural arteriovenous fistulas (dAVFs) having cortical venous drainage. These symptoms are the consequence of cortical venous hypertension and portend a clinical course with increased risk of neurological morbidity and mortality. One rarely documented and easily misinterpreted type of nonhemorrhagic neurological deficit is progressive dementia, which can result from venous hypertension in the cortex or in bilateral thalami. The latter, which is due to dAVF drainage into the deep venous system, is the less common of these 2 dementia syndromes. Herein, the authors report 4 cases of dAVF with venous drainage into the vein of Galen causing bithalamic edema and rapidly progressive dementia. Two patients were treated successfully with endovascular embolization, and the other 2 patients were treated successfully with endovascular embolization followed by surgery. The radiographic abnormalities and presenting symptoms rapidly resolved after dAVF obliteration in all 4 cases. Detailed descriptions of these 4 cases are presented along with a critical review of 15 previously reported cases. In our analysis of these 19 published cases, the following were emphasized: 1) the clinical and radiographic differences between dAVF-induced thalamic versus cortical dementia syndromes; 2) the differential diagnosis and necessary radiographic workup for patients presenting with a rapidly progressive thalamic dementia syndrome; 3) the frequency at which delays in diagnosis occurred and potentially dangerous and avoidable diagnostic procedures were used; and 4) the rapidity and completeness of symptom resolution following dAVF treatment.

Risks and outcomes of spinal deformity surgery in Chiari malformation, Type 1, with syringomyelia versus adolescent idiopathic scoliosis.

BACKGROUND CONTEXT: Chiari malformation, Type 1, with syringomyelia (CIM+SM) is often associated with spinal deformity. The safety of scoliosis surgery this population is controversial and has never been directly compared with adolescent idiopathic scoliosis (AIS). PURPOSE: The purpose of this study was to compare the safety and subjective outcomes of spinal deformity surgery between patients with Chiari malformation Type 1-associated scoliosis and a matched AIS cohort. STUDY DESIGN: This study is based on a retrospective matched cohort analysis. PATIENT SAMPLE: Patients with CIM+SM and treated with spinal fusion for spinal deformity were identified in the surgical records of a single institution and were matched, 1:1, with AIS patients undergoing spinal fusion at the same institution. OUTCOME MEASURES: The outcome measures were neurological monitoring data quality and integrity, radiographic parameters, and Scoliosis Research Society Questionnaire-22 (SRS-22) scores. METHODS: A clinical database was reviewed for patients undergoing spinal reconstruction for CIM+SM-associated spinal deformity at our institution from 2000 to 2012. Thirty-six CIM+SM patients were identified and matched to an AIS cohort (1:1) based on age, gender, major curve magnitude, fusion length, and revision status. Demographics, deformity morphology, surgical details, neuromonitoring data, and preoperative and postoperative SRS-22 scores were recorded at a minimum of 2-year follow-up. Changes in SRS-22 scores were compared within and between groups. Complications and neurological monitoring data issues were compared between groups. RESULTS: Mean age was 14.5±5 years (CIM+SM: 14.6±5; AIS: 14.4±5), and 42% of patients were male. Preoperative mean major coronal Cobb measured 58°±25° versus 57°±17° (p=.84) with mean kyphosis 52°±17° versus 41°±20° (p=.018). An average of 10.4±2.6 vertebral levels were fused (10.4±2.8 vs. 10.4±2.3, p=.928). No differences existed in surgical approach (p=.336), estimated blood loss (680±720 vs. 660±310 mL, p=.845), or duration of surgery (6.0±2.2 vs. 5.6±2 hours, p=.434). Complication rate was comparable between the two groups (33% vs. 14%, p=.052). Chiari malformation, Type 1, with syringomyelia experienced more neurological complications (11% vs. 0%, p=.04) and neuromonitoring difficulties (28% vs. 3%, p=.007) than the AIS cohort. Mean curve correction was comparable at 2 years (58% CIM+SM vs. 64% AIS, p=.2). At follow-up, both CIM+SM and AIS groups demonstrated improved cumulative SRS-22 outcome subscores (CIM+SM: +0.4, p=.027; AIS: +0.3, p<.001). No difference in outcome subscores existed between CIM+SM and AIS groups. CONCLUSIONS: Although CIM+SM patients undergoing spine reconstruction can expect similar deformity corrections and outcome scores to AIS patients, they also experience higher rates of neuromonitoring difficulties and neurological complications related to surgery. Surgeons should be prepared for these difficulties, particularly in children with larger syrinx size.

Atlantoaxial subluxation and nasopharyngeal necrosis complicating suspected granulomatosis with polyangiitis.

Granulomatosis polyangiitis (GPA, formerly Wegener granulomatosis) is a vasculitis that typically involves the upper respiratory tract, lungs, and kidneys. The 2 established methods to confirm a suspicion of GPA are the antineutrophil cytoplasmic antibody (ANCA) test and biopsy. However, ANCA-negative cases have been known to occur, and it can be difficult to find biopsy evidence of granulomatous disease.We report a case of suspected granulomatosis with polyangiitis limited to the nasopharynx. With a negative ANCA and no histological evidence, our diagnosis was founded on the exclusion of other diagnoses and the response to cyclophosphamide therapy. This case is unique because the patient's lesion resulted in atlantoaxial instability, which required a posterior spinal fusion at C1-C2. This is the first reported case of suspected GPA producing damage to the cervical spine and threatening the spinal cord.

Intrasite vancomycin powder for the prevention of surgical site infection in spine surgery: a systematic literature review.

BACKGROUND CONTEXT: Deep surgical site infections (SSIs) following spinal surgery are a significant burden to the patient, patient's family, and the health-care system. Because of increasing pressures to reduce SSIs and control costs, some spine surgeons have begun placing lyophilized vancomycin powder directly into the surgical wound at the conclusion of the procedure. However, the literature supporting this practice remains limited. PURPOSE: To review the current literature examining the use of prophylactic intrasite vancomycin powder to control SSIs in spinal surgery and determine if any standard recommendations can be made. STUDY DESIGN: A systematic review. METHODS: Ovid Medline and PubMed were searched to identify English language articles. RESULTS: No current guidelines are available for the use of intrasite vancomycin powder in preventing SSIs, and no standard dosage for the drug exists. Based on the limited literature and evidence currently available, there appears to be a protective effect of intrasite vancomycin powder on the incidence of SSI, without evidence of side effects. However, case reports do exist describing the systemic side effects after intrasite vancomycin powder during spine surgery. CONCLUSIONS: The interpretation of the available evidence supporting the use of intrasite vancomycin powder in surgical wounds is limited, and its extrapolation should be performed with caution. Despite the lack of significant high-quality evidence available in the literature, many surgeons have adopted this practice; anecdotally, it continues to provide protection from infection without apparent significant risk of side effects.

Surgical management of complex multiloculated hydrocephalus in infants and children.

OBJECTIVE: Multiloculated hydrocephalus may occur as a consequence of intraventricular hemorrhage or infection and is characterized by enlargement of multiple noncommunicating intraventricular and/or periventricular cysts. In this study, we report the outcomes of open and endoscopic fenestration for multiloculated hydrocephalus at our institution. METHODS: Records of children who underwent endoscopic or open fenestration at St. Louis Children's Hospital from 1999 to 2011 were analyzed. The cause of MLH, operative parameters, length of hospital stay, and subsequent shunt intervention rate were recorded. RESULTS: Twenty-five subjects were identified for study. Twelve subjects underwent open craniotomy and 13 underwent endoscopic fenestration. Endoscopic fenestration was associated with decreased blood loss, operative time, and length of stay (p = 0.003, 0.002, 0.02, respectively). Subjects undergoing craniotomy had an average of 5.1 ± 4.5 subsequent shunt-related interventions versus 3.1 ± 4.0 in the endoscopy group (p = 0.25). The craniotomy group's median subsequent shunt revision rate was 0.74 interventions per year versus 0.50 interventions per year in the endoscopy group (p = 0.51). Fifty percent of subjects in the open fenestration group required additional fenestration surgery compared to 38.5% in the endoscopic group (p = 0.70). CONCLUSION: Both open and endoscopic fenestration appeared effective at improving shunt management. The endoscopic technique may offer advantages in operative time, blood loss, and length of hospital stay. These data suggest that endoscopic fenestration may be used as the initial approach for treatment of multiloculated hydrocephalus, with craniotomy and open fenestration used for more severe or refractory cases.

Relationship of syrinx size and tonsillar descent to spinal deformity in Chiari malformation Type I with associated syringomyelia.

OBJECT: Chiari malformation Type I (CM-I) is a developmental abnormality often associated with a spinal syrinx. Patients with syringomyelia are known to have an increased risk of scoliosis, yet the influence of specific radiographically demonstrated features on the prevalence of scoliosis remains unclear. The primary objective of the present study was to investigate the relationship of maximum syrinx diameter and tonsillar descent to the presence of scoliosis in patients with CM-I-associated syringomyelia. A secondary objective was to explore the role of craniovertebral junction (CVJ) characteristics as additional risk factors for scoliosis. METHODS: The authors conducted a retrospective review of pediatric patients evaluated for CM-I with syringomyelia at a single institution in the period from 2000 to 2012. Syrinx morphology and CVJ parameters were evaluated with MRI, whereas the presence of scoliosis was determined using standard radiographic criteria. Multiple logistic regression was used to analyze radiological features that were independently associated with scoliosis. RESULTS: Ninety-two patients with CM-I and syringomyelia were identified. The mean age was 10.5 ± 5 years. Thirty-five (38%) of 92 patients had spine deformity; 23 (66%) of these 35 patients were referred primarily for deformity, and 12 (34%) were diagnosed with deformity during workup for other symptoms. Multiple regression analysis revealed maximum syrinx diameter > 6 mm (OR 12.1, 95% CI 3.63-40.57, p < 0.001) and moderate (5-12 mm) rather than severe (> 12 mm) tonsillar herniation (OR 7.64, 95% CI 2.3-25.31, p = 0.001) as significant predictors of spine deformity when controlling for age, sex, and syrinx location. CONCLUSIONS: The current study further elucidates the association between CM-I and spinal deformity by defining specific radiographic characteristics associated with the presence of scoliosis. Specifically, patients presenting with larger maximum syrinx diameters (> 6 mm) have an increased risk of scoliosis.

Delayed synostoses of uninvolved sutures after surgical treatment of nonsyndromic craniosynostosis.

BACKGROUND: Craniosynostosis causes significant cranial deformity in the pediatric population. Open and endoscopic-assisted surgeries have led to increasingly successful management of this condition. Following surgical reconstruction, subsequent development of postnatal synostosis of previously patent sutures have been described and noted to be most frequently associated with multisuture synostosis patients with syndromic diagnoses. Very rarely, postsurgical new sutural fusion has been identified in nonsyndromic patients who initially present with isolated single-suture synostosis. The purpose of this study was to evaluate the incidence of new synostosis among patients who had undergone craniosynostosis reconstruction with either the open or endoscopic technique. METHODS: Patients undergoing open and endoscopic surgery for nonsyndromic craniosynostosis were reviewed. Preoperative and postoperative imaging and clinical information were reviewed, and cases showing progressive cranial deformity were identified. RESULTS: Three (2.1%) of 145 patients undergoing open craniosynostosis surgery and 2 (1.7%) of 121 patients undergoing endoscopic surgery developed delayed fusion of an additional suture during follow-up. This was identified at a median of 16.4 months after initial surgery in the open group and 15.25 months after surgery in the endoscopic group. In patients undergoing open surgery, each patient developed new sagittal synostosis after initial presentation of coronal synostosis in 1 patient and metopic synostosis in 2 patients. In patients undergoing endoscopic surgery, each patient developed new coronal synostosis after sagittal repair. CONCLUSIONS: Management of craniosynostosis has evolved over time with increasing availability of effective and safe treatments. During long-term follow-up, a small number of patients may develop premature closure of a different suture that did not undergo surgical manipulation. In our case, series, we identified 3 patients undergoing open surgery and 2 patients undergoing endoscopic surgery for nonsyndromic, single-suture craniosynostosis. This finding supports the necessity of long-term clinical follow-up and the utility of delayed imaging when clinical suspicion indicates.

Structural characterization of sulfated steroids that activate mouse pheromone-sensing neurons.

In many species, social behavior is organized via chemical signaling. While many of these signals have been identified for insects, the chemical identity of these social cues (often called pheromones) for mammals is largely unknown. We recently isolated these chemical cues that caused firing in the pheromone-sensing neurons of the vomeronasal organ from female mouse urine [Nodari, F., et al. (2008) J. Neurosci. 28, 6407-6418]. Here, we report their structural characterization. Mass spectrometric approaches, including tandem quadrupole, multiple-stage linear ion trap, high-resolution mass spectrometry, and H-D exchange followed by ESI mass spectrometry, along with (1)H and (13)C nuclear magnetic resonance spectroscopy, including two-dimensional correlation spectroscopy, total correlation spectroscopy, heteronuclear multiple-quantum coherence, and NOE, were used to identify two sulfated steroids, 4-pregnene-11beta,20,21-triol-3-one 21-sulfate (I) (the configuration at C20 was not deduced) and 4-pregnene-11beta,21-diol-3,20-dione 21-sulfate (II), whose presence is sex-specific. The identification of this novel class of mammalian social signaling compounds suggests that steroid hormones, upon conjugation, assume a new biological role, conveying information about the organism's identity and physiological state.

Sulfated steroids as natural ligands of mouse pheromone-sensing neurons.

Among mice, pheromones and other social odor cues convey information about sex, social status, and identity; however, the molecular nature of these cues is essentially unknown. To identify these cues, we screened chromatographic fractions of female mouse urine for their ability to cause reproducible firing rate increases in the pheromone-detecting vomeronasal sensory neurons (VSNs) using multielectrode array (MEA) recording. Active compounds were found to be remarkably homogenous in their basic properties, with most being of low molecular weight, moderate hydrophobicity, low volatility, and possessing a negative electric charge. Purification and structural analysis of active compounds revealed multiple sulfated steroids, of which two were identified as sulfated glucocorticoids, including corticosterone 21-sulfate. Sulfatase-treated urine extracts lost >80% of their activity, indicating that sulfated compounds are the predominant VSN ligands in female mouse urine. As measured by MEA recording, a collection of 31 synthetic sulfated steroids triggered responses 30-fold more frequently than did a similarly sized stimulus set containing the majority of all previously reported VSN ligands. Collectively, VSNs detected all major classes of sulfated steroids, but individual neurons were sensitive to small variations in chemical structure. VSNs from both males and females detected sulfated steroids, but knock-outs for the sensory transduction channel TRPC2 did not detect these compounds. Urine concentrations of the two sulfated glucocorticoids increased many fold in stressed animals, indicating that information about physiological status is encoded by the urine concentration of particular sulfated steroids. These results provide an unprecedented characterization of the signals available for chemical communication among mice.

Fast three-dimensional fluorescence imaging of activity in neural populations by objective-coupled planar illumination microscopy.

Unraveling the functions of the diverse neural types in any local circuit ultimately requires methods to record from most or all of its cells simultaneously. One promising approach to this goal is fluorescence imaging, but existing methods using laser-scanning microscopy (LSM) are severely limited in their ability to resolve rapid phenomena, like neuronal action potentials, over wide fields. Here we present a microscope that rapidly sections a three-dimensional volume using a thin illumination sheet whose position is rigidly coupled to the objective and aligned with its focal plane. We demonstrate that this approach allows exceptionally low-noise imaging of large neuronal populations at pixel rates at least 100-fold higher than with LSM. Using this microscope, we studied the pheromone-sensing neurons of the mouse vomeronasal organ and found that responses to dilute urine are largely or exclusively restricted to cells in the apical layer, the location of V1r-family-expressing neurons.

Multi-germ layer lineage central nervous system repair: nerve and vascular cell generation by embryonic stem cells transplanted in the injured brain.

OBJECT: To restore proper function to a damaged central nervous system (CNS) through transplantation, it is necessary to replace both neural and nonneural elements that arise from different germ layers in the embryo. Mounting evidence indicates the importance of signals related to vasculogenesis in governing neural proliferation and differentiation in early CNS development. Here, the authors examined whether embryonic stem cell (ESC)-derived progenitors can selectively generate both neural and endothelial cells after transplantation in the damaged CNS. METHODS: Injections of 20 nmol N-methyl-D-aspartate created a unilateral striatal injury in 7-day-old rats. One week postinjury, murine ESCs, neural-induced with retinoic acid, were transplanted into the injured striatum. Histological staining, laser confocal microscopy, and transmission electron microscopy of grafted ESCs were performed 1 week posttransplantation. CONCLUSIONS: Transplanted ESCs differentiated into neural cells, which segregated into multiple pools and formed neurons that conformed to host cytoarchitecture. The ESCs also generated endothelial cells, which integrated with host cells to form chimeric vasculature. The combination of ESC pluripotentiality and multiple germ layer differentiation provides a new conceptual framework for CNS repair.

Repair of the injured spinal cord and the potential of embryonic stem cell transplantation.

Traditionally, treatment of spinal cord injury seemed frustrating and hopeless because of the remarkable morbidity and mortality, and restricted therapeutic options. Recent advances in neural injury and repair, and the progress towards development of neuroprotective and regenerative interventions are basis for increased optimism. Neural stem cells have opened a new arena of discovery for the field of regenerative science and medicine. Embryonic stem (ES) cells can give rise to all neural progenitors and they represent an important scientific tool for approaching neural repair. The growing number of dedicated regeneration centers worldwide exemplifies the changing perception towards the do-ability of spinal cord repair and this review was born from a presentation at one such leading center, the Kentucky Spinal Cord Injury Research Center. Current concepts of the pathophysiology, repair, and restoration of function in the damaged spinal cord are presented with an overlay of how neural stem cells, particularly ES cells, fit into the picture as important scientific tools and therapeutic targets. We focus on the use of genetically tagged and selectable ES cell lines for neural induction and transplantation. Unique features of ES cells, including indefinite replication, pluripotency, and genetic flexibility, provide strong tools to address questions of neural repair. Selective marker expression in transplanted ES cell derived neural cells is providing new insights into transplantation and repair not possible previously. These features of ES cells will produce a predictable and explosive growth in scientific tools that will translate into discoveries and rapid progress in neural repair.