Neuronavigation-Specific Parameters for Selective Access of Trigeminal Rootlets in Radiofrequency Lesioning: A Cadaveric Morphometric Study.

BACKGROUND AND OBJECTIVE: Radiofrequency lesioning (RFL) is a safe and effective treatment for medically refractory trigeminal neuralgia. Despite gaining mainstream neurosurgical acceptance in the 1970s, the technique has remained relatively unchanged, with the majority of series using lateral fluoroscopy over neuronavigation for cannula guidance. To date, there are no studies describing neuronavigation-specific parameters to help neurosurgeons selectively target individual trigeminal rootlets. In this cadaveric study, we sought to provide a neuronavigation-specific morphometric roadmap for selective targeting of individual trigeminal rootlets. METHODS: Embalmed cadaveric specimens were registered to cranial neuronavigation. Frontotemporal craniotomies were then performed to facilitate direct visualization of the Gasserian ganglion. A 19-gauge cannula was retrofit to a navigation probe, permitting real-time tracking. Using preplanned trajectories, the cannula was advanced through foramen ovale (FO) to the navigated posterior clival line (nPCL). A curved electrode was inserted to the nPCL and oriented inferolaterally for V3 and superomedially for V2. For V1, the cannula was advanced 5 mm distal to the nPCL and the curved electrode was reoriented inferomedially. A surgical microscope was used to determine successful contact. Morphometric data from the neuronavigation unit were recorded. RESULTS: Twenty RFL procedures were performed (10R, 10L). Successful contact with V3, V2, and V1 was made in 95%, 90%, and 85% of attempts, respectively. Mean distances from the entry point to FO and from FO to the clival line were 7.61 cm and 1.26 cm, respectively. CONCLUSION: In this proof-of-concept study, we found that reliable access to V1-3 could be obtained with the neuronavigation-specific algorithm described above. Neuronavigation for RFL warrants further investigation as a potential tool to improve anatomic selectivity, operative efficiency, and ultimately patient outcomes.

Cardiac-Related Spinal Cord Tissue Motion at the Foramen Magnum is Increased in Patients with Type I Chiari Malformation and Decreases Postdecompression Surgery.

OBJECTIVE: Type 1 Chiari malformation (CM-I) is a craniospinal disorder historically defined by cerebellar tonsillar position greater than 3-5 mm below the foramen magnum (FM). This definition has come under question because quantitative measurements of cerebellar herniation do not always correspond with symptom severity. Researchers have proposed several additional radiographic diagnostic criteria based on dynamic motion of fluids and/or tissues. The present study objective was to determine if cardiac-related craniocaudal spinal cord tissue displacement is an accurate indicator of the presence of CM-I and if tissue displacement is altered with decompression. METHODS: A cohort of 20 symptomatic patients underwent decompression surgery. Fifteen healthy volunteers were recruited for comparison with the CM-I group. Axial phase-contrast magnetic resonance imaging (PC-MRI) measurements were collected before and after surgery at the FM with cranial-caudal velocity encoding and 20 frames per cardiac cycle with retrospective reconstruction. Spinal cord motion (SCM) at the FM was quantified based on the peak-to-peak integral of average spinal cord velocity. RESULTS: Tissue motion for the presurgical group was significantly greater than controls (P = 0.0009). Motion decreased after surgery (P = 0.058) with an effect size of -0.151 mm and a standard error of 0.066 mm. Postoperatively, no statistical difference from controls in bulk displacement at the FM was found (P = 0.200) after post hoc testing using the Tukey adjustment for multiple comparisons. CONCLUSIONS: These results support SCM measurement by PC-MRI as a possible noninvasive radiographic diagnostic for CM-I. Dynamic measurement of SCM provides unique diagnostic information about CM-I alongside static quantification of tonsillar position and other intracranial morphometrics.

CNS Hemangiopericytoma: A Systematic Review of 523 Patients.

BACKGROUND: Central nervous system (CNS) hemangiopericytomas are rare mesenchymal tumors of the brain. In the absence of randomized clinical trials or large studies, the only information we have about the natural history and the management is from isolated clinical case series. They have suggested that surgery is beneficial, with conflicting results on the role of complete resection and adjuvant radiation. We have conducted a systematic review of clinical case series of CNS hemangiopericytoma analyzing the biology of the tumor and the best follow-up and management strategy. METHODS: Fifteen pertinent clinical case series on newly diagnosed CNS hemangiopericytoma were selected by a review of literature. A total of 523 patients were analyzed for age, sex, mode of recurrence and metastases, and survival after complete/incomplete resection with or without radiation. RESULTS: The mean age was found to be 44.17 (±3.59) years. The incidence was higher in male individuals younger than 45 years and in older female individuals. Complete resection and adjuvant radiation significantly improved survival in comparison with incomplete resection and no radiation, respectively (P<0.0001). Furthermore, a significant trend of the tumor to recur locally compared with extraneural and neural axis metastases was noted (P<0.0001). The mean time for distant metastases was seen to be 91.33 (±12.66) months. CONCLUSIONS: Complete resection followed by adjuvant radiation improves survival. Extraneural metastases, especially to lung, bone, and liver, are not uncommon and can occur late in the disease course for which continued follow-up is required. There is also a need to establish a systemic treatment regimen to control the distant metastases.

Spinal sealant system provides better intraoperative watertight closure than standard of care during spinal surgery: a prospective, multicenter, randomized controlled study.

STUDY DESIGN: Prospective, 3:1 randomized, single-blind, multicenter investigational study. OBJECTIVE: To assess the safety and efficacy of a low-swell spinal sealant when used as an adjunct to sutured dural repair compared with standard of care methods to obtain watertight dural closure in subjects undergoing spinal surgery. SUMMARY OF BACKGROUND DATA: Watertight dural closure is paramount in spinal surgery to avoid complications of cerebrospinal fluid leak. Prior reports have proven the efficacy of a synthetic, absorbable polyethylene glycol (PEG) hydrogel sealant in spinal surgery compared with standard of care. Given the potential concerns of swelling in spinal applications, the hydrogel was modified to a low-swell formulation. METHODS: The primary endpoint was success rate in obtaining intraoperative watertight dural closure in subjects receiving PEG hydrogel sealant versus a control group of subjects receiving any standard method designed to provide intraoperative watertight closure. Subjects were evaluated at discharge and at 30 and 90 days postprocedure for cerebrospinal fluid leaks, surgical site infections, and adverse events. RESULTS: Between May 2007 and May 2009, 98 subjects (74 PEG hydrogel spinal sealant, 24 control) were randomized at 14 clinical sites in the United States. Patients treated with the PEG hydrogel spinal sealant had a significantly higher rate of watertight closure than the control (98.6% vs. 79.2%, P = 0.003). No statistical differences were seen in postoperative cerebrospinal fluid, infection, and wound healing. No neurological deficits were seen attributable to the sealant. CONCLUSION: The low-swell PEG hydrogel spinal sealant evaluated in this study has been proven safe and effective for providing watertight closure when used as an adjunct to sutured closure of intentional durotomies during spinal surgery. PEG hydrogel sealants have again proved superior to other standard of care technologies for safe, efficacious dural closure. LEVEL OF EVIDENCE: 2.

Multi-therapeutic potential of autoantibodies induced by immune complexes trapped on follicular dendritic cells.

Induction of autoantibodies (autoAbs) targeting disease drivers / mediators is emerging as a potential immunotherapeutic strategy. Auto-immune complex (IC)-retaining follicular dendritic cells (FDCs) critically regulate pathogenic autoAb production in autoreactive germinal centers (GCs); however, their ability to induce potentially therapeutic autoAbs has not been explored. We hypothesized that deliberate display of clinically targeted antigens (Ags) in the form of ICs on FDC membranes induces target-specific autoreactive GCs and autoAbs that may be exploited therapeutically. To test our hypothesis, three therapeutically relevant Ags: TNF-α, HER2/neu and IgE, were investigated. Our results indicated that TNF-α-, HER2/neu- and IgE-specific autoAbs associated with strong GC reactions were induced by TNF-α-, HER2/neu- and IgE-IC retention on FDCs. Moreover, the induced anti-TNF-α autoAbs neutralized mouse and human TNF-α with half maximal Inhibitory Concentration (IC50) of 7.1 and 1.6 nM respectively. In addition, we demonstrated that FDC-induced Ab production could be non-specifically inhibited by the IgG-specific Endo-S that accessed the light zones of GCs and interfered with FDC-IC retention. In conclusion, the ability of FDCs to productively present autoAgs raises the potential for a novel immunotherapeutic platform targeting mediators of autoimmune disorders, allergic diseases, and Ab responsive cancers.

Measuring surgical outcomes in neurosurgery: implementation, analysis, and auditing a prospective series of more than 5000 procedures.

OBJECT: Health care reform debate includes discussions regarding outcomes of surgical interventions. Yet quality of medical care, when judged as a health outcome, is difficult to define because of impediments affecting accuracy in data collection, analysis, and reporting. In this prospective study, the authors report the outcomes for neurosurgical treatment based on point-of-care interactions recorded in the electronic medical record (EMR). METHODS: The authors' neurosurgery practice collected outcome data for 19 physicians and ancillary personnel using the EMR. Data were analyzed for 5361 consecutive surgical cases, either elective or emergency procedures, performed during 2009 at multiple hospitals, offices, and an ambulatory spine surgery center. Main outcomes included complications, length of stay (LOS), and discharge disposition for all patients and for certain frequently performed procedures. Physicians, nurses, and other medical staff used validated scales to record the hospital LOS, complications, disposition at discharge, and return to work. RESULTS: Of the 5361 surgical procedures performed, two-thirds were spinal procedures and one-third were cranial procedures. Organization-wide compliance with reporting rates of major complications improved throughout the year, from 80.7% in the first quarter to 90.3% in the fourth quarter. Auditing showed that rates of unreported complications decreased from 11% in the first quarter to 4% in the fourth quarter. Complication data were available for 4593 procedures (85.7%); of these, no complications were reported in 4367 (95.1%). Discharge dispositions reported were home in 86.2%, rehabilitation center in 8.9%, and nursing home in 2.5%. Major complications included culture-proven infection in 0.61%, CSF leak in 0.89%, reoperation within the same hospitalization in 0.38%, and new neurological deficits in 0.77%. For the commonly performed procedures, the median hospital LOS was 3 days for craniotomy for aneurysm or intraaxial tumor and less than 1 day for angiogram, anterior cervical discectomy with fusion, or lumbar discectomy. CONCLUSIONS: With prospectively collected outcome data for more than 5000 surgeries, the authors achieved their primary end point of institution-wide compliance and data accuracy. Components of this process included staged implementation with physician pilot studies and oversight, nurse participation, point-of-service data capture, EMR form modification, data auditing, and confidential surgeon reports.

A multicenter, single-blind, prospective randomized trial to evaluate the safety of a polyethylene glycol hydrogel (Duraseal Dural Sealant System) as a dural sealant in cranial surgery.

OBJECTIVE: Incisional cerebrospinal fluid (CSF) leakage after cranial surgery is a significant cause of morbidity due to poor wound healing and infection, meningitis, and pseudomeningocele formation. Many common dural closure techniques, such as sutures, autologous grafts, gelatin or collagen sponges, and fibrin glues, are used to achieve watertight closure, although none are US Food and Drug Administration approved for this use. DuraSeal Dural Sealant System is a polyethylene glycol (PEG) hydrogel approved by the U.S. Food and Drug Administration for obtaining watertight dural closure when applied after standard dural suturing. This multicenter, prospective randomized study further evaluated the safety of a PEG hydrogel compared with common dural sealing techniques. METHODS: A total of 237 patients undergoing elective cranial surgery at 17 institutions were randomized to dural closure augmented with the PEG hydrogel or a control "standard of care" dural sealing technique after Valsalva maneuver demonstrated an intraoperative nonwatertight dural closure. Data were collected on complications resulting in unplanned postoperative interventions or reoperations, surgical site infections, CSF leaks, and other neurological complications within 30 days. Surgeons also provided data on the ease of use of the dural sealing techniques, as well as preparation and application times. RESULTS: The incidences of neurosurgical complications, surgical site infections, and CSF leaks were similar between treatment and control groups, with no statistically significant difference between the measures. In the PEG hydrogel group (n = 120), the incidence of neurosurgical complications was 5.8% (n = 7), the incidence of surgical site infections was 1.7% (n = 2), and the incidence of CSF leak was 0.8% (n = 1). In the control group (n = 117), the incidence of neurosurgical complications was 7.7% (n = 9), the incidence of surgical site infection was 2.6% (n = 3), and the incidence of CSF leak was 1.7% (n = 2). Sealant preparation time was less than 5 minutes in 96.6% of the PEG hydrogel group compared with 66.4% of controls (P < 0.001). The dural augmentation was applied in less than 1 minute in 85.7% of the PEG hydrogel group compared with 66.4% of the control group (P < 0.001). CONCLUSIONS: The PEG hydrogel dural sealant used in this study has a similar safety profile to commonly used dural sealing techniques when used as dural closure augmentation in cranial surgery. The PEG hydrogel dural sealant demonstrated faster preparation and application times than other commonly used dural sealing techniques.

Anatomic study of the prechiasmatic sulcus and its surgical implications.

To address a lack of anatomical descriptions in the literature regarding the prechiasmatic sulcus, we conducted an anatomical study of this sulcal region and discuss its clinical relevance to cranial base surgery. Our systematic morphometric analysis includes the variable types of chiasmatic sulcus and a classification schema that has surgical implications. We examined the sulcal region in 100 dry skulls; bony relationships measured included the interoptic distance, sulcal length/width, planum sphenoidale length, and sulcal angle. The varied anatomy of the prechiasmatic sulcii was classified as four types in combinations of wide to narrow, steep to flat. Its anterior border is the limbus sphenoidale at the posterior aspect of the planum sphenoidale. The sulcus extends posteriorly to the tuberculum sellae and laterally to the posteromedial aspect of each optic strut. Averages included an interoptic distance (19.3 +/- 2.4 mm), sulcal length (7.45 +/- 1.27 mm), planum sphenoidale length (19 +/- 2.35 mm), and sulcal angle (31 +/- 14.2 degrees). Eighteen percent of skulls had a chiasmatic ridge, a bony projection over the chiasmatic sulcus. The four types of prechiasmatic sulcus in our classification hold potential surgical relevance. Near the chiasmatic ridge, meningiomas may be hidden from the surgeon's view during a subfrontal or pterional approach. Preoperative evaluation by thin-cut CT scans of this region can help detect this ridge.

Activation of B cells by antigens on follicular dendritic cells.

A need for antigen-processing and presentation to B cells is not widely appreciated. However, cross-linking of multiple B cell receptors (BCRs) by T-independent antigens delivers a potent signal that induces antibody responses. Such BCR cross-linking also occurs in germinal centers where follicular dendritic cells (FDCs) present multimerized antigens as periodically arranged antigen-antibody complexes (ICs). Unlike T cells that recognize antigens as peptide-MHC complexes, optimal B cell-responses are induced by multimerized FDC-ICs that simultaneously engage multiple BCRs. FDC-FcgammaRIIB mediates IC-periodicity and FDC-BAFF, FDC-IL-6 and FDC-C4bBP are co-stimulators. Remarkably, specific antibody responses can be induced by FDC-ICs in the absence of T cells, opening up the exciting possibility that people with T cell insufficiencies may be immunized with T-dependent vaccines via FDC-ICs.

ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo.

The proteolytic activity of a disintegrin and metalloproteinase 10 (ADAM10) regulates cell-fate decisions in Drosophila and mouse embryos. However, in utero lethality of ADAM10(-/-) mice has prevented examination of ADAM10 cleavage events in lymphocytes. To investigate their role in B cell development, we generated B cell-specific ADAM10 knockout mice. Intriguingly, deletion of ADAM10 prevented development of the entire marginal zone B cell (MZB) lineage. Additionally, cleavage of the low affinity IgE receptor, CD23, was profoundly impaired, but subsequent experiments demonstrated that ADAM10 regulates CD23 cleavage and MZB development by independent mechanisms. Development of MZBs is dependent on Notch2 signaling, which requires proteolysis of the Notch2 receptor by a previously unidentified proteinase. Further experiments revealed that Notch2 signaling is severely impaired in ADAM10-null B cells. Thus, ADAM10 critically regulates MZB development by initiating Notch2 signaling. This study identifies ADAM10 as the in vivo CD23 sheddase and an important regulator of B cell development. Moreover, it has important implications for the treatment of numerous CD23- and Notch-mediated pathologies, ranging from allergy to cancer.

Maximizing the extent of tumor resection during transsphenoidal surgery for pituitary macroadenomas: can endoscopy replace intraoperative magnetic resonance imaging?

OBJECT: Endoscopic approaches to pituitary tumors have become an effective alternative to traditional microscopic transsphenoidal approaches. Despite a proven potential to decrease unexpected residual tumor, intraoperative MR (iMR) imaging is infrequently used even in the few operating environments in which such technology is available. Its use is prohibitive because of its cost, increased complexity, and longer operative times. The authors assessed the potential of intrasellar endoscopy to replace the need for iMR imaging without sacrificing the maximum extent of resection. METHODS: In this retrospective study, 27 consecutive patients underwent fully endoscopic resection of pituitary macroadenomas. Intrasellar endoscopy was used to determine the presence of residual tumor within the sella turcica and tumor cavity. Intraoperative MR imaging was used to identify rates of unexpected residual tumor and the need for further tumor resection. RESULTS: Intraoperative estimates of the extent of tumor resection were correct in 23 patients (85%). Of 4 patients with unacceptable tumor residuals, 3 underwent further tumor resection. After iMR imaging, the rate of successful completion of the planned extent of resection increased to 26 patients (96%). Rates of both endocrinopathy reversal and postoperative complications were consistent with previously published results for microscopic and endoscopic resection techniques. CONCLUSIONS: The findings in this study provided quantitative evidence that intrasellar endoscopy has significant promise for maximizing the extent of tumor resection and is a useful adjunct to surgical approaches to pituitary tumors, particularly when iMR imaging is unavailable. A larger prospective study on the extent of resection following endoscopic transsphenoidal surgery would strengthen these findings.

The safety and effectiveness of a dural sealant system for use with nonautologous duraplasty materials.

OBJECT: The DuraSeal dural sealant system, a polyethylene glycol hydrogel, has been shown to be safe and effective when used with commercial and autologous duraplasty materials. The authors report on the safety and effectiveness of this sealant when used in conjunction with nonautologous duraplasty materials. METHODS: In this retrospective, nonrandomized, multicenter study, the safety and efficacy of a dural sealant system was assessed in conjunction with primarily collagen-based nonautologous duraplasty materials in a sample of 66 patients undergoing elective cranial procedures at 3 institutions. This cohort was compared with 50 well-matched patients from the DuraSeal Pivotal Trial who were treated with this sealant system and autologous duraplasty material. RESULTS: The key end points of the study were the incidences of CSF leaks, surgical site infections, and meningitis 90 days after surgery. The incidence of postoperative CSF leakage was 7.6% in the study group (retrospective population) and 6.0% in the Pivotal Trial population. The incidence of meningitis was 0% and 4.0% in the retrospective and Pivotal Trial groups, respectively. There were no serious device-related adverse events or unanticipated adverse device effects noted for either population. CONCLUSIONS: This study demonstrates that the DuraSeal sealant system is safe and effective when used for watertight dural closure in conjunction with nonautologous duraplasty materials.

IL-6 produced by immune complex-activated follicular dendritic cells promotes germinal center reactions, IgG responses and somatic hypermutation.

Reports that follicular dendritic cells (FDCs) produce IL-6 prompted the hypotheses that immune complexes (ICs) induce FDCs to produce IL-6 and that FDC-IL-6 promotes germinal center (GC) reactions, somatic hypermutation (SHM) and IgG production. FDCs were activated in vitro by addition of ICs and FDC-IL-6 production was determined. Wild-type (WT) and IL-6 knockout (KO) mice, as well as chimeras with WT and IL-6 KO cells, were immunized with (4-hydroxy-3-nitrophenyl)-acetyl (NP)-chicken gamma globulin (CGG) and used to study anti-(4-hydroxy-3-iodo-5-nitrophenyl) acetyl (NIP) responses, GC formation and SHM in the VH186.2 gene segment in Ig-gamma. FDC-IL-6 increased when FDCs encountered ICs. At low immunogen dose, 1 microg NP-CGG per mouse, the IgG anti-NIP response in IL-6 KO mice was low and immunohistochemistry revealed a reduction in both the number and size of GCs. The physiological relevance of FDC-IL-6 was apparent in the chimeric mice where total splenocytes from WT mice were unable to provide the IL-6 needed for normal IgG and GC responses in IL-6 KO animals with IL-6-defective FDCs. Moreover, the rate of mutation decreased from 18 to 8.9 mutations per 1000 bases (P < 0.001) in WT versus IL-6 KO mice. Addition of anti-IL-6 to GC reactions in vitro reduced antibody levels and SHM from 3.5 to 0.65 mutations per 1000 bases (P < 0.02). Thus, the absence of FDC-IL-6 correlated with a reduction in SHM that coincided with the reduction in GCs and specific anti-NIP. This is the first study to document that ICs induce FDC-IL-6 and that FDC-derived IL-6 is physiologically relevant in generating optimal GC reactions, SHM and IgG levels.

T-independent antibody responses to T-dependent antigens: a novel follicular dendritic cell-dependent activity.

Follicular dendritic cells (FDCs) periodically arrange membrane-bound immune complexes (ICs) of T-dependent Ags 200-500A apart, and in addition to Ag, they provide B cells with costimulatory signals. This prompted the hypothesis that Ag in FDC-ICs can simultaneously cross-link multiple BCRs and induce T cell-independent (TI) B cell activation. TI responses are characterized by rapid IgM production. OVA-IC-bearing FDCs induced OVA-specific IgM in anti-Thy-1-pretreated nude mice and by purified murine and human B cells in vitro within just 48 h. Moreover, nude mice immunized with OVA-ICs exhibited well-developed GL-7(+) germinal centers with IC-retaining FDC-reticula and Blimp-1(+) plasmablasts within 48 h. In contrast, FDCs with unbound-OVA, which would have free access to BCRs, induced no germinal centers, plasmablasts, or IgM. Engagement of BCRs with rat-anti-mouse IgD (clone 11-26) does not activate B cells even when cross-linked. However, B cells were activated when anti-IgD-ICs, formed with Fc-specific rabbit anti-rat IgG, were loaded on FDCs. B cell activation was indicated by high phosphotyrosine levels in caps and patches, expression of GL-7 and Blimp-1, and B cell proliferation within 48 h after stimulation with IC-bearing FDCs. Moreover, anti-IgD-IC-loaded FDCs induced strong polyclonal IgM responses within 48 h. Blockade of FDC-FcgammaRIIB inhibited the ability of FDC-ICs to induce T-independent IgM responses. Similarly, neutralizing FDC-C4BP or -BAFF, to minimize these FDC-costimulatory signals, also inhibited this FDC-dependent IgM response. This is the first report of FDC-dependent but TI responses to T cell-dependent Ags.

Mature dendritic cells in inflamed human pulps beneath deep caries.

OBJECTIVE: Dendritic cells (DCs) in pulps have been identified with markers for immature DCs and the relationship of DC maturity to pulpal health has not been carefully examined. We sought to test the hypothesis that the frequency of CD83+ mature DCs would correlate with caries invasion. STUDY DESIGN: Pulps were collected from extracted teeth exhibiting (I) no caries (n = 9), (II) shallow dentinal caries (n = 5), and (III) deep caries (n = 9). Immature DCs (CD209+), mature DCs (CD83+), and monocytes/macrophages (CD14+) in three groups were enumerated immunohistochemically. RESULTS: Mature DCs were frequently found beneath deep caries (21.3 mature DCs/3 grids versus <1 in groups I and II) with increasing numbers of CD209+ DCs and CD14+ cells. Co-localization of CD4+ T cells with mature DCs and macrophages was observed in deep caries. CONCLUSION: Mature DCs were frequently found only beneath deep caries and these DCs were co-localized with CD4+ T cells suggesting antigen presentation.

Delayed extrusion of hydroxyapatite cement after transpetrosal reconstruction.

OBJECTIVE: Use of hydroxyapatite cement has been advocated for closure of transpetrosal defects to decrease the incidence of cerebrospinal fluid leaks. We previously identified delayed extrusion of this cement as a significant complication associated with this closure technique and now update our long-term experience. METHODS: In our retrospective review, we identified 1231 patients who underwent transpetrosal procedures by our multidisciplinary cranial base team between 1984 and 2005. Of the subgroup of 177 patients who had hydroxyapatite cement used during the closure of the procedure, 13 patients (7.3%) experienced delayed extrusion of hydroxyapatite cement. RESULTS: Extrusion occurred in 3 patients within 12 months and in 10 patients within 68 to 140 months. Twelve patients presented with draining fistulae and concomitant Staphylococcus aureus infection; 1 patient presented asymptomatically with a large temporal lobe abscess identified on surveillance magnetic resonance imaging. All 13 patients underwent reoperation, including 1 who underwent a second procedure. CONCLUSION: Delayed extrusion of hydroxyapatite cement resulted in significant morbidity to our patients and often presented in an indolent manner. We recommend serial examination and imaging studies in patients who have had transpetrosal closures with hydroxyapatite cement. Because of the complication rates associated with hydroxyapatite cement, we have discontinued its use.

Extension of the one-piece orbitozygomatic frontotemporal approach to the glenoid fossa: cadaveric study.

OBJECTIVE: Resection of the glenoid fossa has been described as part of cranial approaches to the clivus and subtemporal approaches. However, radical resection carries a significant risk of postoperative temporomandibular joint dysfunction. We examine a simple variation of our previously described one-piece frontotemporal orbitozygomatic (FTOZ) osteotomy that adds en bloc resection of the root of the zygomatic arch and a portion of the glenoid fossa. METHODS: Five cadaveric fixed heads injected with colored silicone underwent an FTOZ osteotomy that extended to the root of the zygomatic arch and glenoid fossa. RESULTS: A step-by-step guide to the surgical technique is described, with illustrations to depict the glenoid fossa keyhole and bony cuts that free the zygomatic arch and portions of glenoid fossa. The first cut was made through the posterior root, and the second cut was made through the anterior root of the zygomatic arch. CONCLUSION: In this cadaveric study, extension of the one-piece FTOZ approach included the posterior root of the zygoma and the lateral part of the glenoid fossa. En bloc resection of the glenoid fossa and root of the zygomatic arch, together with the FTOZ osteotomy, facilitated reconstruction of the temporomandibular joint and increased the amount of exposure obtained with this FTOZ osteotomy. Comprehensive understanding of functional outcomes awaits further clinical study.

Ultrastructural study of highly enriched follicular dendritic cells reveals their morphology and the periodicity of immune complex binding.

Follicular dendritic cells (FDCs) are immune accessory cells found in the follicles of secondary lymphoid organs where they promote B cell maturation in germinal centers (GCs) that develop following antigen exposure. Recently, we published a method for isolating functional murine FDCs in high purity. We reasoned that disruption of FDC reticula in vivo would alter FDC morphology. The present study was undertaken to determine the morphological features of isolated FDCs. FDC-M1 and immune complex (IC) labeling were used to identify FDCs in isolated preparations. Results at the light-microscopic level revealed that isolated FDCs trapped ICs, expressed FDC-M1 and cadherins, but generally appeared non-dendritic. However, at the ultrastructural level, the majority of FDCs exhibited dendrites and typical euchromatic nuclei that appeared as single, bilobed, or double nuclei. Based on morphology, four varieties of FDCs were distinguishable, possibly indicative of differences in maturity. Remarkably, ICs trapped by FDCs showed a distinctive periodic arrangement consistent with that known to induce immune responses by thymus independent-2 (TI-2) antigens that engage and cross-link multiple B cell receptors. The ability of FDCs to trap ICs and then display these T-cell-dependent antigens with repeating periodicity suggests that multiple B cell receptors are cross-linked by antigen on FDCs, thus promoting B cell stimulation and proliferation. Rapid proliferation is characteristic of the GC reaction, and the arrangement of T-dependent antigens in this periodic fashion may help to explain the profuse B cell proliferation in the GC microenvironment.

Evolution in the assessment and management of trigeminal schwannoma.

EDUCATIONAL OBJECTIVE: At the conclusion of this presentation, the participants should be able to understand the contemporary assessment and management algorithm used in the evaluation and care of patients with trigeminal schwannomas. OBJECTIVES: 1) Describe the contemporary neuroradiographic studies for the assessment of trigeminal schwannoma; 2) review the complex skull base osteology involved with these lesions; and 3) describe a contemporary management algorithm. STUDY DESIGN: Retrospective review of 23 cases. METHODS: Chart review. RESULTS: From 1984 to 2006, of 23 patients with trigeminal schwannoma (10 males and 13 females, ages 14-77 years), 15 patients underwent combined transpetrosal extirpation, 5 patients underwent stereotactic radiation, and 3 were followed without intervention. Of the 15 who underwent surgery, total tumor removal was achieved in 9 patients. Cytoreductive surgery was performed in six patients; of these, four received postoperative radiation. One patient who underwent primary radiation therapy required subsequent surgery. There were no deaths in this series. Cranial neuropathies were present in 14 patients pretreatment and observed in 17 patients posttreatment. Major complications included meningitis (1), cerebrospinal fluid leakage (2), major venous occlusion (1), and temporal lobe infarction (1). CONCLUSIONS: Trigeminal schwannomas are uncommon lesions of the skull base that may occur in the middle fossa, posterior fossa, or both. Moreover, caudal extension results in their presentation in the infratemporal fossa. Contemporary diagnostic imaging, coupled with selective use of both surgery and radiation will limit morbidity and allow for the safe and prudent management of this uncommon lesion.

Immune complex-bearing follicular dendritic cells deliver a late antigenic signal that promotes somatic hypermutation.

We reasoned that immune complex (IC)-bearing follicular dendritic cells (FDCs) promote somatic hypermutation (SHM). This hypothesis was tested in murine germinal center reactions induced in vitro by coculturing 6-day (4-hydroxy-3-nitrophenyl) acetyl-primed but unmutated lambda+ B cells, chicken gamma-globulin (CGG) memory T cells, FDCs, and ICs (anti-CGG plus NP-CGG). Mutations in primed lambda+ B cells were obtained only when both FDCs and immunogen were present. FDCs alone promoted B cell survival and Ab production but there were no mutations without more immunogen. Moreover, the mutation rate was enhanced when FDCs were activated. Trapped ICs ranged from 200 to 500 A apart on FDC membranes and this correlated with the periodicity known to optimally signal BCRs. FDCs are unique in their ability to retain ICs for months and a second signal mediated by FDC-ICs appeared to be needed a week or more after immunization by immunogen persisting on FDCs. However, the time needed to detect extensive SHM could be reduced to 7 days if ICs were injected together with memory T cells in vivo. In marked contrast, no mutations were apparent after 7 days in vivo if ICs were replaced by free Ag that would not load on FDCs until Ab was produced. The data suggest that specific Ab production leads to the following events: Ab encounters Ag and ICs are formed, ICs are trapped by FDCs, B cells are stimulated by periodically arranged Ag in ICs on FDCs, and this late antigenic signal promotes SHM.