Herpes simplex meningitis after vestibular schwannoma surgery: illustrative case.

BACKGROUND: Herpes is the most common cause of viral encephalitis in the young population. Herpes meningitis following brain surgery is very rare, however. Only a few cases are reported in the literature, and only one concerned an infection after vestibular schwannoma surgery. OBSERVATIONS: The authors report a case of a 44-year-old patient who developed severe herpes meningitis a few days after removal of a large cystic vestibular schwannoma. LESSONS: Herpes simplex virus meningitis following a posterior fossa surgery must be considered when patients develop atypical symptoms a few days after surgery.

Change in Off-Label Use of Bone Morphogenetic Protein in Spine Surgery and Associations with Adverse Outcome.

Study Design Retrospective cohort study. Objective The U.S. Food and Drug Administration issued a warning in 2008 against off-label bone morphogenetic protein (BMP-2) use. We aimed to determine (off-label) BMP-2 use in two periods and associations with complications. Methods We included 340,393 patients undergoing spinal fusions from the Premier Perspective database (2006 to 2012). BMP-2 use was determined from billing in 2006 to 2008 versus 2009 to 2012. Outcomes included revisions, length of hospital stay (LOHS), and cost of hospital stay (COH). Multilevel regressions measured associations between BMP-2 and outcomes; odds ratios (ORs) and 95% confidence intervals (CIs) are reported. Results BMP-2 use decreased from 18.7% in 2006 to 11.5% in 2012. Off-label use remains but is decreasing, particularly for cervical anterior (5.1 versus 2.0%) and cervical posterior procedures (15.3 versus 8.5%; both p < 0.01 comparing 2006 to 2008 with 2009 to 2012). BMP-2 remains associated with increased LOHS (median 2 versus 3 days; both periods) and COH (median $15,455 versus $27,881 in 2006 to 2008; $17,007 versus $30,331 in 2009 to 2012). Adjusted ORs for the association between BMP-2 and adverse outcomes were generally lower in 2009 to 2012 compared with 2006 to 2008. Most notably, we demonstrate lower ORs for revision after cervical fusions in 2009 to 2012 (OR 1.67, CI 1.01 to 2.78) compared with 2006 to 2008 (OR 2.43, CI 1.66 to 3.54). Conclusions Using a previously untapped data source, we show decreased (off-label) BMP-2 use in spinal fusions, particularly in cervical fusions. Although there was a tendency of decreased odds in 2009 to 2012, higher resource utilization and odds for complications remain in patients using BMP-2. A national registry or prospective observational studies will benefit the ongoing discussion.

Does the impact of the type of anesthesia on outcomes differ by patient age and comorbidity burden?

INTRODUCTION: Neuraxial anesthesia may provide perioperative outcome benefits versus general anesthesia in orthopedic surgical patients. As subgroup analyses are lacking, we evaluated the influence of the type of anesthesia on outcomes in patient groups of different age and the presence of cardiopulmonary disease. METHODS: Data from approximately 500 hospitals in the United States regarding total hip and total knee arthroplasties performed between 2006 and 2012 were accessed. Patients were categorized by age (ie, <65, 65-74, or ≥75 years) as well as the presence of cardiopulmonary disease. Resulting groups were compared with regard to patient, hospital, procedure, and comorbidity-related variables, as well as incidence of major perioperative complications. A multivariable logistic regression analysis was performed to assess the independent influence of the type of anesthesia on complications within each patient subgroup. RESULTS: We identified 795,135 records of patients who underwent total hip arthroplasty or total knee arthroplasty. The incidence of major complications was highest in the oldest patient group with cardiopulmonary disease (26.1%) and the lowest in the youngest group without cardiopulmonary disease (4.5%).Multivariable logistic regressions showed that neuraxial anesthesia was associated with decreased odds for combined major complications, need for intensive care services, and prolonged length of stay compared with general anesthesia in all patient subgroups. For patients without major cardiopulmonary comorbidities, the positive impact of neuraxial anesthesia increased with increasing age. CONCLUSIONS: Neuraxial anesthesia is associated with decreased odds for major complications and resource utilization after joint arthroplasty for all patient groups, irrespective of age and comorbidity burden.

Perioperative mortality after lumbar spinal fusion surgery: an analysis of epidemiology and risk factors.

STUDY DESIGN: Analysis of the Nationwide Inpatient Sample (NIS) from 1998 to 2008. OBJECTIVE: To analyze the most recent available and nationally representative data for risk factors contributing to in-hospital mortality after primary lumbar spine fusion. SUMMARY OF BACKGROUND DATA: The total number of lumbar spine fusion surgeries has increased dramatically over the past decades. While the field of spine fusion surgery remains highly dynamic with changes in perioperative care constantly affecting patient care, recent data affecting rates and risk for perioperative mortality remain very limited. METHODS: We obtained the NIS from the Hospital cost and utilization project. The impact of patient and health care system related demographics, including various comorbidities as well as postoperative complications on the outcome of in-hospital mortality after spine fusion were studied. Furthermore, we analyzed the timing of in-hospital mortality. RESULTS: An estimated total of 1,288,496 primary posterior lumbar spine fusion procedures were performed in the US between 1998 and 2008. The average mortality rate for lumbar spine fusion surgery was 0.2%. Independent risk factors for in-hospital mortality included advanced age, male gender, large hospital size, and emergency admission. Comorbidities associated with the highest in-hospital mortality after lumbar spine fusion surgery were coagulopathy, metastatic cancer, congestive heart failure and renal disease. Most lethal complications were cerebrovascular events, sepsis and pulmonary embolism. Furthermore, we demonstrated that the timing of death occurred relatively early in the in-hospital period with over half of fatalities occurring by postoperative day 9. CONCLUSION: This study provides nationally representative information on risk factors for and timing of perioperative mortality after primary lumbar spine fusion surgery. These data can be used to assess risk for this event and to develop targeted intervention to decrease such risk.

Perioperative morbidity and mortality after anterior, posterior, and anterior/posterior spine fusion surgery.

STUDY DESIGN: Analysis of population-based national hospital discharge data collected for the National Inpatient Sample. OBJECTIVE: To examine demographics of patients undergoing primary anterior spine fusion (ASF), posterior spine fusion (PSF), and anterior/posterior spine fusion (APSF) of the noncervical spine, assess the incidence of perioperative morbidity and mortality, and determine independent risk factors for in-hospital death. SUMMARY OF BACKGROUND DATA: The utilization of surgical fusion has been increasing dramatically. Despite this trend, a paucity of literature addressing perioperative outcomes exists. METHODS: Data collected for each year between 1998 and 2006 for the National Inpatient Sample were analyzed. Discharges with a procedure code for primary noncervical spine fusion were included in the sample. The prevalence of patient as well as health care system-related demographics were evaluated by procedure type (ASF, PSF, and APSF). Frequencies of procedure-related complications and in-hospital mortality were analyzed. Independent predictors for in-hospital mortality were determined. RESULTS: We identified 261,256 entries representing an estimated 1,273,228 hospitalizations for primary spine fusion. Patients undergoing ASF and APSF were significantly younger (44.8 ± 0.08 and 44.22 ± 0.11 years) and had lower average comorbidity indeces (0.30 ± 0.002 and 0.31 ± 0.004) than those undergoing PSF (52.12 ± 0.04 years and 0.41 ± 0.002) (P < 0.0001). The incidence of procedure-related complications was 18.68% among ASF, 15.72% in PSF, and 23.81% in APSF patients (P < 0.0001). In-hospital mortality rates after APSF were approximately twice those of PSF (0.51 ± 0.038 vs. 0.26 ± 0.012) (P < 0.0001). Adjusted risk factors for in-hospital mortality included the following: APSF and ASF compared to PSF, male gender, increasing age, and increasing comorbidity burden. Several comorbidities and complications independently increased the risk for perioperative death, as did underlying spinal pathology. CONCLUSION: Despite being performed in generally younger and healthier patients, APSF and ASF are associated with increased morbidity and mortality. Our findings can be used for the purposes of risk stratification, accurate patient consultation, and hypothesis formation for future research.

Materials and techniques for osseous skull reconstruction.

This review paper gives an overview and summarizes the different methods of cranioplasty for reconstruction of the bony skull. There are various origins of cranial defects including trauma, tumours, congenital deformities or postoperative defects due to the surgical procedure itself. The overall goal of skull reconstruction is, on the one hand, appropriate closure, and on the other hand, the perfect cosmetic result. The cranioplasty should be safe, fast and easy to handle. Cost-effectiveness of the procedure represents a further important point. To solve these complex and multimodal problems, different techniques and also various materials for the reconstruction are available. This report details the usual procedures for skull reconstruction, as well as the advantages and limitations of the different materials and operative strategies.

Wallerian degeneration and axonal regeneration after sciatic nerve crush are altered in ICAM-1-deficient mice.

The intercellular cell adhesion molecule-1 (ICAM-1) has been implicated in the recruitment of immune cells during inflammatory processes. Previous studies investigating its involvement in the process of Wallerian degeneration and focusing on its potential role in macrophage recruitement have come to controversial conclusions. To examine whether Wallerian degeneration is altered in the absence of ICAM-1, we have analyzed changes in the expression of axonal and Schwann cell markers following sciatic nerve crush in wildtype and ICAM-1-deficient mice. We report that the lack of ICAM-1 leads to impaired axonal degeneration and regeneration and to alterations in Schwann cell responses following sciatic nerve crush. Degradation of neurofilament protein, the collapse of axonal profiles, and the re-expression of neurofilament proteins are substantially delayed in the distal nerve segment of ICAM-1(-/-) mice. In contrast, the degradation of myelin, as determined by immunostaining for myelin protein zero, is unaltered in the mutants. Upregulation of GAP-43 and p75 neurotrophin receptor (p75(NTR)) expression, characteristic for Schwann cells dedifferentiating in response to nerve injury, is differentially altered in the mutant animals. These results indicate that ICAM-1 is essential for the normal progression of axonal degeneration and regeneration in distal segments of injured peripheral nerves.

Minimally invasive dorsal percutaneous spondylodesis for the treatment of adult pyogenic spondylodiscitis.

BACKGROUND: Most adult patients with pyogenic lumbar or thoracic spondylodiscitis are treated with an external orthosis and antimicrobial therapy for several weeks to months. If surgical intervention is required, a combined anterior and posterior approach for debridement and fusion with autologous bone graft or titanium mesh cage is usually performed. METHOD: We here report on our experience with the use of a minimally invasive percutaneous dorsal pedicle screw-rod spondylodesis in adult patients with pyogenic lumbar or thoracic spondylodiscitis. FINDINGS: Eight patients with lumbar, one with thoracolumbar and three with thoracic pyogenic spondylodiscitis with a mean back pain of 9/10 on the visual analog scale (VAS) and without corresponding neurological deficits were treated. Immediately after the operation, we calculated a significant reduction of the back pain on the VAS to 1.7, of leukocyte counts and C-reactive protein levels. After a mean of 61 days of continuous antimicrobial therapy during full mobilization, all patients were pain free, and leukocyte counts as well as C-reactive protein levels were normalized. CONCLUSIONS: We conclude that minimally invasive percutaneous fixation is a feasible and effective technique to achieve immediate pain release, avoid long-term immobilization and overcome the disadvantages of a dorsoventral procedure. However, surgical complications and possible follow-up procedures supplement the patients' risks of adverse reactions of the disease.

Surgical removal of a symptomatic paracondylar process.

The paracondylar process is a rare congenital abnormality of the craniocervical junction that has been identified as a causative agent for severe headache, neck pain, and restricted head movement. Although conservative treatment is usually sufficient, the authors report the case of a symptomatic paracondylar process in a young patient who required surgical intervention.

Candidate genes for sensitivity and resistance of human glioblastoma multiforme cell lines to erlotinib. Laboratory investigation.

OBJECT: The authors have previously reported that erlotinib, an EGFR tyrosine kinase inhibitor, exerts widely variable antiproliferative effects on 9 human glioblastoma multiforme (GBM) cell lines in vitro and in vivo. These effects were independent of EGFR baseline expression levels, raising the possibility that more complex genetic properties form the molecular basis of the erlotinib-sensitive and erlotinib-resistant GBM phenotypes. The aim of the present study was to determine candidate genes for mediating the cellular response of human GBMs to erlotinib. METHODS: Complementary RNA obtained in cell lines selected to represent the sensitive, somewhat responsive, and resistant phenotypes were hybridized to CodeLink Human Whole Genome Bioarrays. RESULTS: Expression analysis of 814 prospectively selected genes involved in major proliferation and apoptosis signaling pathways identified 19 genes whose expression significantly correlated with phenotype. Functional annotation analysis revealed that 2 genes (DUSP4 and STAT1) were significantly associated with sensitivity to erlotinib, and 10 genes (CACNG4, FGFR4, HSPA1B, HSPB1, NFATC1, NTRK1, RAC1, SMO, TCF7L1, and TGFB3) were associated with resistance to erlotinib. Moreover, 5 genes (BDNF, CARD6, FOSL1, HSPA9B, and MYC) involved in antiapoptotic pathways were unexpectedly found to be associated with sensitivity. Gene expressions were confirmed by quantitative polymerase chain reaction. CONCLUSIONS: Based on an analysis of gene expressions in cell lines with sensitive, somewhat responsive, and resistant phenotypes, the authors propose candidate genes for GBM response to erlotinib. The 10 gene candidates for conferring GBM resistance to erlotinib may represent therapeutic targets for enhancing the efficacy of erlotinib against GBMs. Five additional genes warrant further investigation into their role as putative cotargets of erlotinib.

Image guided percutaneous trans-pedicular screw fixation of the thoracic spine. A clinical evaluation.

OBJECTIVE: We report our preliminary experience with a minimally invasive image guided percutaneous trans-pedicular fixation technique of the thoracic spine in patients with significant co-morbidity. This study aims to demonstrate the feasibility and efficacy of the presented operative technique as well as to detect potential drawbacks. METHOD: A navigated percutaneous application of trans-pedicular screws was performed in 14 patients with radiological validated instability of the thoracic spine and significant medical co-morbidity. Due to poor bone quality, vertebroplasty of the affected levels had to be performed in nine patients. The levels involved were (T9-12) in ten patients, the middle (T5-8) in two patients and the upper thoracic (T1-4) segments in two others. VAS scores for local back pain were used to assess clinical outcome. RESULTS: A total of 56 screws were inserted. There was no additional morbidity associated with the procedure. Post-operative CT scans and plain X-rays were obtained in all patients. In 2 (3.5%) medial penetration of the pedicle border occurred without neurological sequelae for the patient. Reduction of VAS scores regarding back pain during the first post-operative week was noted. Follow up ranged between 6 months and 12 months. CONCLUSION: Navigated percutaneous trans-pedicular fixation of the thoracic spine is feasible and can be performed safely in patients where open surgery is of significant risk. Pre-operative planning is essential in order to avoid intra-operative complications with the instrumentation system.

Pathogenetic pathways leading to glioblastoma multiforme: association between gene expressions and resistance to erlotinib.

BACKGROUND: The antiproliferative effects of erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, on human glioblastoma multiforme (GBM) cell lines in vitro and in vivo are widely variable and independent of EGFR baseline expression levels, indicating that more complex genetic signatures may form the molecular basis of GBM response to erlotinib. This study sought to determine which genes within two common genetic pathways of GBM pathogenesis, i.e., the primary and secondary pathways, may be involved in mediating the cellular response of human GBM towards erlotinib. MATERIALS AND METHODS: Complementary (c)RNAs from cell lines selected to represent the sensitive, intermediately responsive and resistant phenotypes, respectively, were hybridized to CodeLink Human Whole Genome Bioarrays. RESULTS: Expression analysis of prospectively selected 104 genes pertaining to the primary and secondary pathways of GBM pathogenesis identified two genes (IGF1, PIK3C2B) the expression of which significantly correlated with cellular resistance towards erlotinib. CONCLUSION: Among the genes constituting two common pathways of GBM pathogenesis, two candidate genes may confer GBM resistance towards erlotinib, suggesting that resistance towards this compound may be acquired during the natural evolution of GBM.

Epidermal growth factor receptor pathway gene expressions and biological response of glioblastoma multiforme cell lines to erlotinib.

BACKGROUND: Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, exerts highly variable antiproliferative effects on human glioblastoma multiforme (GBM) cells in vitro and in vivo. As these effects are independent of EGFR baseline expression levels, more complex genetic signatures may form the molecular basis of the erlotinib-sensitive and erlotinib-resistant GBM phenotypes. The aim of the current study was to determine which genes within the EGFR signaling pathway are candidates for mediating the cellular response of human GBM towards erlotinib. MATERIALS AND METHODS: Complementary (c)RNAs from cell lines selected to represent the sensitive, intermediately responsive and resistant phenotypes, respectively, were hybridized to CodeLink Human Whole Genome Bioarrays. RESULTS: Expression analysis of the prospectively selected 244 genes whose products constitute the EGFR signaling pathway identified five genes the expression of which significantly correlated with phenotype. Functional annotation analysis revealed one (STATI) and two (FKBP14, RAC1) genes conclusively associated with sensitivity and resistance to erlotinib, respectively. Moreover, two additional genes (PTGER4, MYC) were unexpectedly found to be associated with sensitivity. The gene expressions were confirmed by quantitative polymerase chain reaction. CONCLUSION: Five genes within the EGFR signaling pathway may modulate GBM response to erlotinib, which further emphasizes the importance of this pathway for the biology of GBM.

Transient intradural catheter lysis in a patient with a diffuse and elongated subdural hematoma of the spine due to trauma. Case report.

The often extended and elongated configuration of a diffuse subdural hematoma of the spine makes it impossible to completely evacuate with common neurosurgical approaches. The authors describe the complete evacuation of a diffuse subdural hematoma of the entire spine due to trauma in a patient who suffered myelopathy and paraplegia in succession, by using transient subdural catheter lysis. After the patient underwent a partial hemilaminectomy at T7-8 and L2-3 using a lateral transmuscular approach, a 15 cm-long intraventricular catheter was inserted at each hemilaminectomy site and connected to an external ventricular drainage system in a procedure lasting 1 hour. Subsequently, 5000 IU of urokinase was applied four times daily for 30 minutes each time over the next 5 days. Two months later, the patient presented with spastic paraparesis Manual Muscle Test Grade 4/5. Magnetic resonance (MR) imaging revealed no catheter-related complications. The authors conclude from this case that transient catheter lysis may be an effective and gentle method to treat diffuse and elongated subdural hematomas of the spine due to trauma. A larger series needs to be analyzed, however, to address the indications and limitations of the technique compared with conventional open surgery. Such evaluation should include serial MR imaging and electrophysiological examination.

Percutaneous transforaminal lumbar interbody fusion for the treatment of degenerative lumbar instability.

OBJECTIVE: Percutaneous spinal instrumentation techniques may be helpful to reduce approach-related morbidity inherent to conventional open surgery. This article reports technique, clinical outcomes, and fusion rates of percutaneous transforaminal lumbar interbody fixation (pTLIF). Results are compared with those of mini-open transforaminal lumbar interbody fixation (oTLIF) using a muscle splitting (Wiltse) approach. METHODS: pTLIF was performed in 43 patients with single-level and 10 patients with bi- or multilevel lumbar discopathy or degenerative pseudolisthesis resulting in axial back pain and claudication, pseudoradicular, or radicular symptoms. Decompression, discectomy, and interbody cage insertion were performed through 18-mm tubular retractors followed by percutaneous pedicle screw-rod fixation. Clinical outcome was assessed by early postoperative pain scores (visual analog score) and standardized functional outcome questionnaires (American Academy of Orthopedic Surgeons lumbar spine and Roland-Morris low back pain score). Fusion rates were assessed by thin-slice computed tomographic scan at 16 months. Clinical outcome, time in the operating room, intraoperative blood loss, and postoperative access-site pain were compared with an institutional reference series of 67 oTLIF procedures. RESULTS: Excellent and good clinical results were obtained in 46 (87%) out of 53 patients at 16 months. The time spent in the operating room was equivalent and the blood loss reduced compared with oTLIF (P < 0.01). There was no morbidity related to instrumentation. Postoperative pain was significantly lower after pTLIF after the second postoperative day (P < 0.01). The overall clinical outcome was not different from oTLIF at 8 and 16 months. CONCLUSION: pTLIF allows for safe and efficient minimally invasive treatment of single and multilevel degenerative lumbar instability with good clinical results. Further prospective studies investigating long-term functional results are required to assess the definitive merits of percutaneous instrumentation of the lumbar spine.

Monitoring motor function during resection of tumours in the lower brain stem and fourth ventricle.

OBJECTIVES: Even in the days of modern microsurgery, the removal of a brain stem lesion remains a surgical challenge. Especially when operating on children, the prognosis is directly related to the radicality of the resection; however, a radical resection is often associated with surgical morbidity. Intraoperative neuromonitoring could help to minimise the surgical morbidity, but few studies have been performed to clarify the value of this monitoring. We investigated a prospective series of 21 patients with lesions involving the brain stem for the prognostic value and benefits of neuromonitoring. METHODS: We performed intraoperative neuromonitoring of cranial nerve function by electromyography (EMG) and motor evoked potential (MEP). The results were correlated with postoperative neurological deficits. CONCLUSIONS: There is a good correlation between intraoperative neurophysiological events and postoperative neurological deficits in patients with lesions of the brain stem. In general, transient, prolonged, spontaneous activity in EMG is associated with a transient paresis of the respective muscle, whereas a permanent spontaneous activity is associated with a permanent deficit. Intraoperative neuromonitoring reliably predicts postoperative neurological function in patients with tumours of the lower brain stem and fourth ventricle. This neuromonitoring guides the neurosurgeon in the operation and may decrease surgical morbidity. We recommend using monitoring of MEP and EMG of the lower cranial nerves in surgery on all patients with lesions involving the lower brain stem and fourth ventricle.

Uniform MDM2 overexpression in a panel of glioblastoma multiforme cell lines with divergent EGFR and p53 expression status.

BACKGROUND: Overexpression and deletion mutation of the epidermal growth factor receptor (EGFR) gene, as well as murine double minute 2 (MDM2) overexpression have been linked to the absence of p53 gene mutations in human glioblastoma multiforme (GBM). MATERIALS AND METHODS: EGFR and MDM2 messenger (m)RNA expression profiles and p53 status were examined by reverse transcription-polymerase chain rection (RT-PCR) and gene sequencing, respectively, in a set of human wild-type (wt) p53 GBM cell lines (U-87MG, U-87MG.wtEGFR and U-87MG.deltaEGFR) that exclusively differ in EGFR expression (endogenous wt EGFR expression, exogenous wt EGFR overexpression and exogenous 801-bp deletion-mutant [delta] EGFR overexpression, respectively), as well as in two human mutant p53 GBM cell lines that differ approximately two-fold in endogenous wt EGFR mRNA expression. RESULTS: Regardless of the underlying heterogeneity in EGFR mRNA expression and p53 status, MDM2 was similarly overexpressed among the cell lines. CONCLUSION: These data suggest that in human GBM (i) overexpression of wt or deltaEGFR and of MDM2 may constitute independent genetic events, (ii) overexpression of wt EGFR and mutation of p53 in GBM, although considered mutually exclusive in vivo, are not reciprocally prohibitive per se, and (iii) p53 mutations do not necessarily preclude MDM2 overexpression. In addition, this set of human GBM cell lines may constitute a suitable model for evaluating MDM2-targeted therapies in the context of various accompanying genetic alterations.