Morphometric subaxial lateral mass evaluation allows for preoperative optimal screw trajectory planning.

PURPOSE: Lateral mass (LM) fixation has become a standard in cervical spine instability treatment; however, maximal biomechanical stability combined with low morbidity remains a challenge. We evaluated our own patient cohort for bicortical screw placement and complication rates and investigated optimal screw trajectories with preoperative multiplanar computed tomography (CT) scans. METHODS: Fifty-five patients were retrospectively evaluated after LM fixation at various subaxial cervical spine levels with a modified Magerl technique. Postoperative CTs and clinical records were used to determine LM anatomy, screw lengths, bicortical screw percentages, and complication rates. Additionally, 3D CT subaxial cervical spine data sets from 45 additional subjects with clinical indications for cervical spine imaging were evaluated. Subject LM geometries (thickness) were evaluated at different sagittal angulations (strict sagittal, 20°, 30° and the optimal angulation) for the optimal screw trajectories at the C3-C7 segments. RESULTS: In total, 284 LM screws were placed, with a mean screw length of 16 mm and an 88% bicortical bone purchase. Additionally, a 3.8% malplacement rate was observed. LM thickness varied substantially between each subaxial cervical level and at each of the investigated angulations. The optimal angulation, at which LM thickness was maximal, increased continuously from C3 (14°) to C7 (38°). This increase permitted 8% (C3) to 39% (C7) gains in screw length compared with the strict sagittal plane assessments. CONCLUSIONS: The optimal LM trajectory varied for each subaxial segment. The knowledge of LM geometry allows for safe, long and even bicortical screw placements using preoperative sagittal CT imaging evaluations.

Vascular endothelial growth factor signals through platelet-derived growth factor receptor ß in meningiomas in vitro.

BACKGROUND: Vascular endothelial growth factor (VEGF)-mediated angiogenesis mediates tumour growth and metastasis. Meningiomas are primarily benign, slow-growing, highly vascularised tumours. Aside from VEGF, there is little data on the function of major angiogenic proteins in meningiomas. METHODS: The VEGFA, platelet-derived growth factor B (PDGFB), and their respective receptors - VEGF receptor 2 (KDR) and PDGF receptor ß (PDGFRß) - were quantified using real-time PCR and a TaqMan Protein Assay in meningiomas in vivo and in vitro. The effect of VEGFA and PDGFB on cell proliferation and the tyrosine phosphorylation of PDGFRß were examined. RESULTS: Most meningiomas displayed no KDR protein expression but elevated PDGFRß levels. Exogenous VEGFA stimulation significantly increased cell proliferation. The PDGFRß inhibition before stimulation with VEGFA abolished the proliferative stimuli. The VEGFA induced concentration-dependent PDGFRß tyrosine phosphorylation comparable to PDGFB-induced PDGFRß tyrosine phosphorylation. The PDGFRß inhibitors gambogic acid, sunitinib, and tandutinib equally impaired the migration of meningioma cells. In addition, gambogic acid suppressed the VEGFA-induced PDGFRß tyrosine phosphorylation. CONCLUSION: Collectively, our data suggest that VEGFA primarily regulates VEGF-mediated migration through PDGFRß in meningiomas. The inhibitory effect of gambogic acid and tandutinib against meningioma growth in vitro suggests that selective PDGFRß inhibitors, in combination with VEGF inhibitors, should be evaluated further as potential therapies for recurrent and malignant meningiomas.

Balancing the shortcomings of microscope and endoscope: endoscope-assisted technique in microsurgical removal of recurrent epidermoid cysts in the posterior fossa.

BACKGROUND: We report about endoscope-assisted surgery of epidermoid cysts in the posterior fossa focusing on the application of neuro-endoscopy and the clinical outcome in cases of recurrent epidermoid cysts. MATERIAL AND METHODS: 25 consecutively operated patients with an epidermoid cyst in the posterior fossa were retrospectively analysed. Surgeries were performed both with an operating microscope (OPMI Pentero or NC 4, Zeiss Company, Oberkochen, Germany) and endoscopic equipment (4 mm rigid endoscopes with 30° and 70° optics; Karl Storz Company, Tuttlingen, Germany) under continuous intraoperative monitoring. Surgical reports and DVD-recordings were evaluated for identification of adhesion areas and surgical details. RESULTS: 7 (28%) of the 25 patients were recurrences of previously operated epidermoid cysts. Mean time to recurrence was 17 years (8-22 years). In 5 cases the endoscope was used as an adjunctive tool for inspection/endoscope-assisted removal of remnants. The effective time of use of the endoscope was limited to the end stage of the procedure, but was very effective. CONCLUSION: In a modern operative setting and with the necessary surgical experience recurrent epidermoid cysts may be removed with excellent clinical results. The combined use of microscope and endoscope offers relevant advantages in demanding anatomic situations.

The microglial/macrophagic response at the tumour-brain border of invasive meningiomas.

AIMS: Little is known about the immune response of the brain to invasive meningiomas. The present study was based upon the hypothesis that the microglial/macrophagic response towards brain-invasive meningiomas is dependent on the intactness of the pial-glial basement membrane. METHODS: We immunostained sections from 40 brain-invasive meningiomas that were graded according to World Health Organization (WHO) 2007 criteria. Thirty-three tumours were histologically WHO grade II (18, 'otherwise benign', and 15, 'otherwise atypical'), and seven, grade III. Microglial/macrophagic cells were labelled with antibodies directed against major histocompatibility complex class II, CD68, CD14 and CD163. Anti-collagen IV was used to visualize basement membranes. RESULTS: Twenty-five per cent (10/40) meningiomas (1/18 WHO grade II 'otherwise benign', 3/15 grade II 'otherwise atypical' and 6/7 WHO grade III) contained microglial/macrophagic cells at the tumour-brain border. The presence of these cells correlated with the absence of the pial-glial basement membrane (BM) and with WHO grade III. The monocytic response was of two kinds: one consisted of a dense layer of mononuclear cells at the tumour-brain border in nine cases, the other of an elevated number of microglial cells expressing CD14 or CD163 (two cases). CONCLUSIONS: The immune response at the tumour-brain interface correlates with the absence of the pial-glial BM and with malignancy grade. It remains to be established whether the mononuclear cells at the tumour-brain border are native microglia or blood-derived macrophages.

Erythropoietin receptor is expressed in meningiomas and lower levels are associated with tumour recurrence.

AIMS: The Epo-EpoR pathway plays a role in tumour growth, metastasis and treatment resistance and is a potential target in oncological treatment. As the EpoR status in human meningiomas is unknown, our aim was to characterize EpoR expression in these tumours. METHODS: We examined 131 meningioma samples of all WHO grades from 116 patients by immunohistochemistry for EpoR. Among these, 25 meningiomas showed brain invasion and 29 patients had a further tumour recurrence. A group of 20 patients without tumour recurrence served as controls. In 12 cases we were able to compare both the primary and the following recurrent tumours. The presence of EpoR in meningiomas was confirmed by RT-PCR and Western blot. RESULTS: EpoR was expressed in all meningiomas. Statistical analysis revealed that the mean expression levels of EpoR were significantly lower in primary tumours with known recurrence compared with a recurrence-free control group. Additional matched pair analysis in individual cases showed no significant differences between primary and recurrent tumours. No significant correlation between EpoR expression and WHO grade, age, sex or brain invasion was detected. Using specific primer pairs for RT-PCR, we were able to detect all three known isoforms of EpoR: the full-length isoform EpoR-F, the truncated isoform EpoR-T and the soluble isoform EpoR-S. CONCLUSIONS: Our results demonstrate the expression of EpoR in meningiomas. Lower EpoR mean levels might be a useful marker for a higher recurrence risk, but further studies are needed to clarify the influence of EpoR on recurrences and the role of the different isoforms.

Femtosecond and picosecond laser drilling of metals at high repetition rates and average powers.

The influence of pulse duration on the laser drilling of metals at repetition rates of up to 1 MHz and average powers of up to 70 W has been experimentally investigated using an ytterbium-doped-fiber chirped-pulse amplification system with pulses from 800 fs to 19 ps. At a few hundred kilohertz particle shielding causes an increase in the number of pulses for breakthrough, depending on the pulse energy and duration. At higher repetition rates, the heat accumulation effect overbalances particle shielding, but significant melt ejection affects the hole quality. Using femtosecond pulses, heat accumulation starts at higher repetition rates, and the ablation efficiency is higher compared with picosecond pulses.

Prognosis of stage II colon cancer by non-neoplastic mucosa gene expression profiling.

We have assessed the possibility to build a prognosis predictor (PP), based on non-neoplastic mucosa microarray gene expression measures, for stage II colon cancer patients. Non-neoplastic colonic mucosa mRNA samples from 24 patients (10 with a metachronous metastasis, 14 with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. Patients were repeatedly and randomly divided into 1000 training sets (TSs) of size 16 and validation sets (VS) of size 8. For each TS/VS split, a 70-gene PP, identified on the TS by selecting the 70 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Mean prognosis prediction performances of the 70-gene PP were 81.8% for accuracy, 73.0% for sensitivity and 87.1% for specificity. Informative genes suggested branching signal-transduction pathways with possible extensive networks between individual pathways. They also included genes coding for proteins involved in immune surveillance. In conclusion, our study suggests that one can build an accurate PP for stage II colon cancer patients, based on non-neoplastic mucosa microarray gene expression measures.

500 MW peak power degenerated optical parametric amplifier delivering 52 fs pulses at 97 kHz repetition rate.

We present a high peak power degenerated parametric amplifier operating at 1030 nm and 97 kHz repetition rate. Pulses of a state-of-the art fiber chirped-pulse amplification (FCPA) system with 840 fs pulse duration and 410 microJ pulse energy are used as pump and seed source for a two stage optical parametric amplifier. Additional spectral broadening of the seed signal in a photonic crystal fiber creates enough bandwidth for ultrashort pulse generation. Subsequent amplification of the broadband seed signal in two 1 mm BBO crystals results in 41 microJ output pulse energy. Compression in a SF 11 prism compressor yields 37 microJ pulses as short as 52 fs. Thus, pulse shortening of more than one order of magnitude is achieved. Further scaling in terms of average power and pulse energy seems possible and will be discussed, since both concepts involved, the fiber laser and the parametric amplifier have the reputation to be immune against thermo-optical effects.

Degenerate optical parametric amplifier delivering sub 30 fs pulses with 2GW peak power.

Degenerated optical parametric amplification (OPA) is a well known technique to achieve broadband amplification necessary to generate ultrashort pulses. Here we present a parametric amplifier pumped by the frequency doubled output of a state-of-the-art fiber chirped pulse amplification system (FCPA) delivering mJ pulse energy at 30 kHz repetition rate and 650 fs pulse duration. The parametric amplifier and the FCPA system are both seeded by the same Yb:KGW oscillator. Additional spectral broadening of the OPA seed provides enough bandwidth for the generation of ultrashort pulses. After amplification in two 1mm BBO crystals a pulse energy of 90 microJ is yielded at 30 kHz. Subsequent compression with a sequence of chirped mirrors shortens the pulses to 29 fs while the pulse energy is as high as 81 microJ resulting in 2GW of peak power.

High speed laser drilling of metals using a high repetition rate, high average power ultrafast fiber CPA system.

We present an experimental study on the drilling of metal targets with ultrashort laser pulses at high repetition rates (from 50 kHz up to 975 kHz) and high average powers (up to 68 Watts), using an ytterbium-doped fiber CPA system. The number of pulses to drill through steel and copper sheets with thicknesses up to 1 mm have been measured as a function of the repetition rate and the pulse energy. Two distinctive effects, influencing the drilling efficiency at high repetition rates, have been experimentally found and studied: particle shielding and heat accumulation. While the shielding of subsequent pulses due to the ejected particles leads to a reduced ablation efficiency, this effect is counteracted by heat accumulation. The experimental data are in good qualitative agreement with simulations of the heat accumulation effect and previous studies on the particle emission. However, for materials with a high thermal conductivity as copper, both effects are negligible for the investigated processing parameters. Therefore, the full power of the fiber CPA system can be exploited, which allows to trepan high-quality holes in 0.5mm-thick copper samples with breakthrough times as low as 75 ms.

Single-polarization ultra-large-mode-area Yb-doped photonic crystal fiber.

We report on an ytterbium-doped single-transverse-mode rod-type photonic crystal fiber that combines the advantages of low nonlinearity and intrinsic polarization stability. The mode-field-area of the fundamental mode is as large as 2300 microm(2). An output power of up to 163 W with a degree of polarization better than 85% has been extracted from a simple fiber laser setup without any additional polarizing element within the cavity than the fiber itself. The beam quality has been characterized by a M(2) value of 1.2. The single-polarization window ranges from 1030 to 1080 nm, hence possesses an excellent overlap with the gain profile of ytterbium-doped silica fibers. To the best of our knowledge this fiber design has the largest mode-field-diameter ever reported for polarizing or even polarization maintaining rare-earth-doped double-clad fibers.

Spinal cord compression through extraosseous extension of a vertebral low-grade hemangioendothelioma with histiocytoid differentiation.

Herein, we report the case of a 47-year-old man clinically presenting a slow progressive loss of lower extremity functions within 8 weeks followed by an acute neurogenic bladder dysfunction. The patient exhibited high-grade paralysis of both legs with reduced sensation from dermatome Th11 downwards as well as marked spasticity of the lower extremity. Neuroradiological examinations revealed a protruding spinal tumor with extraosseous-intraspinal extension. The resected tumor mass exhibited a highly vascularized tumor with architectural complexity and high cellularity finally leading to the diagnosis of a hemangioendothelioma. Interesting was the fact that the tumor vasculature exhibited many CD68-positive cells protruding into the lumen and, therefore, being part of a partially histiocytoid differentiation which is all the more uncommon in hemangioendothelioma. The time frame of 3 hours between embolization and tumor resection is too short to explain a monocytic intravascular reaction. Usually, hemangioendotheliomas arise from the soft tissue, lungs or liver, but intraspinal manifestations are only rarely observed. Furthermore, the clinical course with a progressive development of a paraparesis due to a hemangioendothelioma is very uncommon.

Hypericin uptake: a prognostic marker for survival in high-grade glioma.

Currently adjuvant chemotherapy for glioblastoma patients can prolong survival time relative to patients who receive only surgery and radiotherapy. Despite these improvements and experimental and clinical efforts the prognosis for glioblastoma patients remains poor. At present, interest is focused on individual prognostic factors influencing patient responses to therapy. Photodynamic therapy may be a promising therapeutic option in the treatment of glioblastoma. In this investigation we examined whether uptake of hypericin (HY), a fluorescent photosensitization agent, by ex vivo glioblastoma cell lines correlates with prognosis of the individual from which the cell lines were derived. Twelve primary human glioma cell cultures were incubated with 20 micromol HY. Fluorescence intensity was measured using fluorescence microscopy. Three patients suffered from an anaplastic astrocytoma, WHO grade III, nine had a glioblastoma, WHO grade IV. In 6/12 patients complete tumour resection was possible. The mean survival time of the six patients in whom complete tumour resection was performed was 26 months, compared with 5 months for those who underwent incomplete resection. Eleven patients received radiation therapy. The five patients who received chemotherapy survived for a mean duration of 26 months, compared with the seven patients who survived for a mean duration of 5 months without chemotherapy. Statistical analysis using a parametric survival model based on the Weibull distribution showed that fluorescence intensity was the variable with the lowest p-value associated with survival (p=0.0225). An increase of 553 arbitrary units of fluorescence intensity is predicted to double survival time. Uptake of HY, a lipophilic molecule, is assumed to be related to low-density lipoprotein (LDL) uptake and metabolism. Cell proliferation is associated with a high turnover of cholesterol and membrane growth, which is related to cholesterol uptake by LDL. In summary, HY uptake by ex vivo glioblastoma cell cultures seems to be positively associated with survival of patients with malignant glioma.

Endoscope-assisted retrosigmoid intradural suprameatal approach to the middle fossa: anatomical and surgical considerations.

INTRODUCTION: Lesions involving the posterior and middle fossa may be reached by several surgical approaches depending mostly on tumors' location and characteristics. The retrosigmoid intradural suprameatal approach has been used to remove tumors of the posterior fossa extending into Meckel's cave and the middle fossa. With large tumors, this approach may allow exposure of the oculomotor and optic nerves, the supraclinoid internal carotid and communicating posterior arteries. METHODS: Three formaldehyde-fixed specimens have been prepared on both sides using the conventional retrosigmoidal-suprameatal approach. The entire endoscopic preparations have been documented via a digital recording system, using a 5mm endoscope with a 25 degrees perspective. The authors describe the anatomical corridor and technique of the endoscope-assisted retrosigmoid intradural suprameatal approach to lesions that are located predominantly within the posterior fossa and supratentorial extension into Meckel's cave, sellar and parasellar region. CONCLUSIONS: The endoscope-assisted suprameatal approach provides exposure of the antero-medial middle fossa even in cases of skull base lesions that have not caused significant displacement of neurovascular structures.

Management of skull based meningiomas in the elderly patient.

BACKGROUND: The demographic evolution of Western society together with availability of modern imaging techniques leads to an increasing diagnosis of meningioma patients over 70 years of age. This raises the question of appropriate management of this histologically benign tumour in a geriatric population. DESIGN: Forty-three patients aged over 70 years were analyzed and matched in a retrospective study with a younger group of 89 patients according to tumour size, histology, symptoms, recurrence and presence of neurofibromatosis II. RESULTS: Changes in postoperative Karnofsky scores were not statistically different between the two age groups. Neurological outcome was worse among the younger group (12% vs. 7% deterioration). Regarding surgical complications we noted only a statistically significant higher infection rate in the geriatric age group. There was no peri-operative mortality. CONCLUSIONS: Age alone is not a criterion to deny a priori skull base surgery, since well selected geriatric patients may benefit from a meningioma operation that may enhance future quality of life.

Extended single-mode photonic crystal fiber lasers.

We report on an ytterbium-doped photonic crystal fiber with a core diameter of 60 microm and mode-field-area of ~2000 microm(2) of the emitted fundamental mode. Together with the short absorption length of 0.5 m this fiber possesses a record low nonlinearity which makes this fiber predestinated for the amplification of short laser pulses to very high peak powers. In a first continuous-wave experiment a power of 320 W has been extracted corresponding to 550 W per meter. To our knowledge this represents the highest power per unit length ever reported for fiber lasers. Furthermore, the robust single-transverse-mode propagation in a passive 100 microm core fiber with a similar design reveals the potential of extended large-mode-area photonic crystal fibers.

Stress-induced birefringence in large-mode-area micro-structured optical fibers.

We report on detailed numerical investigation of stress-induced birefringence in micro-structured solid-core optical fibers. The stress is induced either by external forces or stress applying parts inside the fiber. Both methods lead to different stress distributions where screening as well as enhancement effects due to the air-hole micro-structuring could be observed. Furthermore, we discuss the potential of the realization of polarization-maintaining low-nonlinearity micro-structured fibers that are suitable for applications in ultrafast optics.

Stress-induced single-polarization single-transverse mode photonic crystal fiber with low nonlinearity.

We report on the design of a single-polarization single-transverse mode large mode area photonic crystal fiber. By including index-matched stress applying elements in the photonic cladding an ultra-broadband single polarization window is obtained while a large mode field area of ~700 microm(2) is maintained. Based on that design, an Yb-doped double-clad photonic crystal fiber is realized that combines low nonlinearity and single polarization properties. A first result of the high power operation using this fiber is demonstrated.

High-power rod-type photonic crystal fiber laser.

We report on a novel ytterbium-doped fiber design that combines the advantages of rod and fiber gain media. The fiber design has outer dimensions of a rod laser, meaning a diameter in the range of a few millimeters and a length of just a few tens of centimeters, and includes two important waveguide structures, one for pump radiation and one for laser radiation. We obtained 120-W output power in single-mode beam quality from a 48-cm-long fiber cane that corresponds to an extracted power of 250 W/m. The fiber has significantly reduced nonlinearity, which therefore allows for scalability in the performance of a high-peak-power fiber laser and amplifier system.

Surgical removal of primary central nervous system lymphomas (PCNSL) presenting as space occupying lesions: a series of 33 cases.

AIMS: In this study we present a series of 33 patients with primary CNS lymphomas (PCNSL), many presenting with acute signs of increased intracranial pressure due to large space occupying lesions. METHODS: A series of 32 PCNSL patients for a total of 33 tumours treated from 1986 to 2000 in the Neurosurgical Department were reviewed. RESULTS: Radiotherapy and chemotherapy improved survival. No benefit could be demonstrated for the role of surgery. CONCLUSIONS: Our data confirm previous reports about the role of radiation and chemotherapy in the treatment of PCNSL's. Surgery might have a role in a selected subset of patients presenting with large single space occupying lesions and deteriorating neurological status.