A transfacet approach to the lumbar nerve root canal: technical note.

BACKGROUND: Intraforaminal and extraforaminal nerve root compressions caused by disk herniation or stenosis are relatively common causes of lumbar radiculopathy. Currently, the two available surgical treatment methods are decompression from the spinal canal or lateral decompression via the Wiltse approach. OBJECTIVE: To describe a novel transosseous approach to the lumbar nerve root canal. METHODS: Transfacet foraminotomy was performed in 11 patients with intraforaminal or extraforaminal disk herniation. The outcome was measured using the Patient Satisfaction Index (PSI), need for reoperation, radiographic criteria, and finite element analysis. RESULTS: We noted that at the time of dismissal, PSI scores of 1 and 3 were reported by 10 and one patients, respectively. At the last follow-up, 10 patients reported a PSI score of 1 or 2. Two patients required reoperation because of recurrent disk herniation. Two patients underwent computed tomography (CT) postoperatively, which showed the transfacet approach. Intriguingly, a second postoperative CT after one month showed that the hole through the facet joint had shrunk significantly. CONCLUSION: A posterior-anterior transfacet approach for intraforaminal or extraforaminal disk herniations using an ellipsoid facetectomy is safe and allows for fast and comfortable decompression of the nerve root without compromising the long-term strength of the facet joint.

Long-Term Reduction of Sacroiliac Joint Pain With Peripheral Nerve Stimulation.

BACKGROUND: We recently demonstrated that 86% of the patients treated with peripheral nerve stimulation (PNS) for therapy-refractory sacroiliac joint (SIJ) pain were satisfied with the result after 1 year of treatment. OBJECTIVE: To investigate the long-term (up to 4 years) response rate of this novel treatment. METHODS: Sixteen consecutive patients with therapy-refractory SIJ pain were treated with PNS and followed for 4 years in 3 patients, 3 years in 6 patients, and 2 years in 1 patient. Quality of life, pain, and patient satisfaction were assessed using the Oswestry Disability Index 2.0, Visual Analog Scale (VAS), and International Patient Satisfaction Index. RESULTS: Patients reported a pain reduction from 8.8 to 1.6 (VAS) at 1 year ( P < .001), and 13 of 14 patients (92.9%) rated the therapy as effective (International Patient Satisfaction Index score ≤ 2). At 2 years, average pain score was 1.9 ( P < .001), and 9 of 10 patients (90.0%) considered the treatment a success. At 3 years, 8 of 9 patients (88.9%) were satisfied with the treatment results, reporting an average VAS of 2.0 ( P < .005). At 4 years, 2 of 3 patients were satisfied with the treatment results. CONCLUSION: We have shown for the first time that PNS is a successful long-term therapy for SIJ pain.

Neonatal hypoxia-ischemia in rat increases doublecortin concentration in the cerebrospinal fluid.

Doublecortin (DCX) is a microtubule-associated protein widely used as an indicator of neurogenesis in immunohistochemical analyses of the postmortem adult brain. A recent study reported that DCX can be quantified in the cerebrospinal fluid (CSF) from healthy rats between postnatal day 0 (P0) and P30. However, it is currently unclear whether the concentration of DCX in the CSF (CSF-DCX) may represent a measure of endogenous neurogenesis. To address this question, this study examined the impact of a neonatal hypoxic-ischemic (HI) brain injury, known to induce neurogenesis, on CSF-DCX. HI was elicited at P7 in Sprague-Dawley rat neonates, and CSF was collected serially from the cisterna magna at P5 and P10, or at P10 and P15. A sandwich immunoassay was used to measure CSF-DCX. Brains from P10 neonates were analyzed immunohistochemically for neurogenesis and cell death markers. Mean CSF-DCX was significantly higher in HI- than in sham-exposed animals, at both P10 and P15. In the HI group at P10, CSF-DCX and stroke severity correlated positively. DCX immunoreactivity was increased in the ipsilateral neurogenic niches from the P10 HI brains in comparison with that of shams. The number of proliferative DCX-positive cells was higher in the ipsilateral hippocampal subgranular zone (SGZ) than in the HI contralateral or sham SGZ. Thus, neonatal HI brain injury disrupts the developmental time-course of DCX levels in the CSF. Our data suggest that the increased concentration of DCX in the CSF after neonatal HI is the result of both cellular injury and increased neurogenesis.

An Enzyme- and Serum-free Neural Stem Cell Culture Model for EMT Investigation Suited for Drug Discovery.

Epithelial to mesenchymal transition (EMT) describes the process of epithelium transdifferentiating into mesenchyme. EMT is a fundamental process during embryonic development that also commonly occurs in glioblastoma, the most frequent malignant brain tumor. EMT has also been observed in multiple carcinomas outside the brain including breast cancer, lung cancer, colon cancer, gastric cancer. EMT is centrally linked to malignancy by promoting migration, invasion and metastasis formation. The mechanisms of EMT induction are not fully understood. Here we describe an in vitro system for standardized isolation of cortical neural stem cells (NSCs) and subsequent EMT-induction. This system provides the flexibility to use either single cells or explant culture. In this system, rat or mouse embryonic forebrain NSCs are cultured in a defined medium, devoid of serum and enzymes. The NSCs expressed Olig2 and Sox10, two transcription factors observed in oligodendrocyte precursor cells (OPCs). Using this system, interactions between FGF-, BMP- and TGFß-signaling involving Zeb1, Zeb2, and Twist2 were observed where TGFß-activation significantly enhanced cell migration, suggesting a synergistic BMP-/TGFß-interaction. The results point to a network of FGF-, BMP- and TGFß-signaling to be involved in EMT induction and maintenance. This model system is relevant to investigate EMT in vitro. It is cost-efficient and shows high reproducibility. It also allows for the comparison of different compounds with respect to their migration responses (quantitative distance measurement), and high-throughput screening of compounds to inhibit or enhance EMT (qualitative measurement). The model is therefore well suited to test drug libraries for substances affecting EMT.

Risk factors for postoperative CSF leakage after elective craniotomy and the efficacy of fleece-bound tissue sealing against dural suturing alone: a randomized controlled trial.

OBJECT: Cerebrospinal fluid leakage is an immanent risk of cranial surgery with dural opening. Recognizing the risk factors for this complication and improving the technique of dural closure may reduce the associated morbidity and its surgical burden. The aim of this paper was to investigate whether the addition of TachoSil on top of the dural suture reduces postoperative CSF leakage compared with dural suturing alone and to assess the frequency and risk factors for dural leakage and potentially related complications after elective craniotomy. METHODS: The authors conducted a prospective, randomized, double-blinded single-center trial in patients undergoing elective craniotomy with dural opening. They compared their standard dural closure by running suture alone (with the use of a dural patch if needed) to the same closure with the addition of TachoSil on top of the suture. The primary end point was the incidence of CSF leakage, defined as CSF collection or any open CSF fistula within 30 days. Secondary end points were the incidence of infection, surgical revision, and length of stay in the intensive care unit (ICU) or intermediate care (IMC) unit. The site of craniotomy, a history of diabetes mellitus, a diagnosis of meningioma, the intraoperative need of a suturable dural substitute, and blood parameters were assessed as potential risk factors for CSF leakage. RESULTS: The authors enrolled 241 patients, of whom 229 were included in the analysis. Cerebrospinal fluid leakage, mostly self-limiting subgaleal collections, occurred in 13.5% of patients. Invasive treatment was performed in 8 patients (3.5%) (subgaleal puncture in 6, lumbar drainage in 1, and surgical revision in 1 patient). Diabetes mellitus, a higher preoperative level of C-reactive protein (CRP), and the intraoperative need for a dural patch were positively associated with the occurrence of the primary end point (p = 0.014, 0.01, and 0.049, respectively). Cerebrospinal fluid leakage (9.7% vs 17.2%, OR 0.53 [95% CI 0.23-1.15], p = 0.108) and infection (OR 0.18 [95% CI 0.01-1.18], p = 0.077) occurred less frequently in the study group than in the control group. TachoSil significantly reduced the probability of staying in the IMC unit for 1 day or longer (OR 0.53 [95% CI 0.27-0.99], p = 0.048). Postoperative epidural hematoma and empyema occurred in the control group but not in the study group. CONCLUSIONS: Dural leakage after elective craniotomy/durotomy occurs more frequently in association with diabetes mellitus, elevated preoperative CRP levels, and the intraoperative need of a dural patch. This randomized controlled trial showed no statistically significant reduction of postoperative CSF leakage and surgical site infections upon addition of TachoSil on the dural suture, but there was a significant reduction in the length of stay in the IMC unit. Dural augmentation with TachoSil was safe and not related to adverse events. Clinical trial registration no. NCT00999999 ( http://www.ClinicalTrials.gov ).

Non-invasive neural stem cells become invasive in vitro by combined FGF2 and BMP4 signaling.

Neural stem cells (NSCs) typically show efficient self-renewal and selective differentiation. Their invasion potential, however, is not well studied. In this study, Sox2-positive NSCs from the E14.5 rat cortex were found to be non-invasive and showed only limited migration in vitro. By contrast, FGF2-expanded NSCs showed a strong migratory and invasive phenotype in response to the combination of FGF2 and BMP4. Invasive NSCs expressed Podoplanin (PDPN) and p75NGFR (Ngfr) at the plasma membrane after exposure to FGF2 and BMP4. FGF2 and BMP4 together upregulated the expression of Msx1, Snail1, Snail2, Ngfr, which are all found in neural crest (NC) cells during or after epithelial-mesenchymal transition (EMT), but not in forebrain stem cells. Invasive cells downregulated the expression of Olig2, Sox10, Egfr, Pdgfra, Gsh1/Gsx1 and Gsh2/Gsx2. Migrating and invasive NSCs had elevated expression of mRNA encoding Pax6, Tenascin C (TNC), PDPN, Hey1, SPARC, p75NGFR and Gli3. On the basis of the strongest upregulation in invasion-induced NSCs, we defined a group of five key invasion-related genes: Ngfr, Sparc, Snail1, Pdpn and Tnc. These genes were co-expressed and upregulated in seven samples of glioblastoma multiforme (GBM) compared with normal human brain controls. Induction of invasion and migration led to low expression of differentiation markers and repressed proliferation in NSCs. Our results indicate that normal forebrain stem cells have the inherent ability to adopt a glioma-like invasiveness. The results provide a novel in vitro system to study stem cell invasion and a novel glioma invasion model: tumoral abuse of the developmental dorsoventral identity regulation.

Comparison of different autografts for aural cartilage in aesthetic rhinoplasty: is the tragal cartilage graft a viable alternative?

Auricular cartilage is an important source of grafts for various reconstructive procedures such as aesthetic rhinoplasty. The purpose of this investigation was to compare tragal cartilage with auricular cartilage harvested from the concha and scapha, and describe its clinical viability, indications, and morbidity in rhinoplasty. A total of 150 augmentation rhinoplasties with a total of 170 grafts were included. The donor sites were tragus (n=136), concha (n=26), and scapha (n=8). The time needed to harvest the grafts, the donor site morbidity, and the indications for operation were recorded. The anthropometric changes to 4 auricular variables after the cartilage had been harvested were analysed and compared with those on the opposite side in 48 patients using Student's paired t-test. Intraobserver reliability was assessed using Pearson's intraclass correlation. The mean (SD) harvesting time was 27 (8) min for the concha, 4.5 (1.4) min for the tragus, and 5.7 (1.6) min for the scapha. The largest graft was taken from the concha (28×19 mm), followed by the tragus (20×12 mm), and the scapha (18×6 mm). The grafts were placed at the following sites: tip grafts (n=123), columella struts (n=80), shield (n=20), rim (n=17), and dorsal onlay (n=15). Harvesting tragal cartilage is safe, simple, fast, and has a low morbidity, but it can affect the patient's ability to wear earphones. Tragal cartilage is a good alternative for nasal reconstruction if a graft of no longer than 20 mm is required.

BMP-2-dependent integration of adult mouse subventricular stem cells into the neural crest of chick and quail embryos.

Central nervous system (CNS) stem cells isolated from the subventricular zone (SVZ) show a remarkable differentiation potential into neural derivatives. Surprisingly adult SVZ cells can also be induced in vitro to differentiate into neural crest cell fates. This fate switch is dependent on the combination of fibroblast growth factor 2 (FGF2) and bone morphogenetic proteins (BMPs). Here we transplanted adult SVZ stem cells from GFP mice as neurospheres into the trunk neural tube of chick and quail embryos. Only neurospheres pre-exposed to BMP-2 and FGF2 formed close contacts with the dorsal neuroepithelium corresponding to the neural crest area. GFP-positive cells emigrated from the neurosphere and were identified in the roof plate, the dorsal neuroepithelium and among emigrating neural crest cells adjacent to the neural tube. Neurospheres not treated with BMP-2 did not integrate into the neuroepithelium. Our data demonstrate that adult CNS stem cells can be efficiently prepared in vitro for integration into the embryonic neural crest. BMP-2 treatment conveys the necessary morphogenetic capabilities to adult stem cells for future clinical transplantation strategies.

BMP2 and FGF2 cooperate to induce neural-crest-like fates from fetal and adult CNS stem cells.

CNS stem cells are best characterized by their ability to self-renew and to generate multiple differentiated derivatives, but the effect of mitogenic signals, such as fibroblast growth factor 2 (FGF2), on the positional identity of these cells is not well understood. Here, we report that bone morphogenetic protein 2 (BMP2) induces telencephalic CNS stem cells to fates characteristic of neural crest and choroid plexus mesenchyme, a cell type of undetermined lineage in rodents. This induction occurs both in dissociated cell culture and cortical explants of embryonic day 14.5 (E14.5) embryos, but only when cells have been exposed to FGF2. Neither EGF nor IGF1 can substitute for FGF2. An early step in this response is activation of beta-catenin, a mediator of Wnt activity. The CNS stem cells first undergo an epithelial-to-mesenchymal transition and subsequently differentiate to smooth-muscle and non-CNS glia cells. Similar responses are seen with stem cells from E14.5 cortex, E18.5 cortex and adult subventricular zone, but with a progressive shift toward gliogenesis that is characteristic of normal development. These data indicate that FGF2 confers competence for dorsalization independently of its mitogenic action. This rapid and efficient induction of dorsal fates may allow identification of positional identity effectors that are co-regulated by FGF2 and BMP2.