[Intraoperative monitoring of the facial nerve : Vestibular schwannoma surgery]. / Intraoperative Funktionsüberwachung des N. facialis : Operationen an Vestibularisschwannomen.

BACKGROUND: In vestibular schwannoma surgery, facial nerve injury with consecutive functional impairment is one of the most important complications. Intraoperative monitoring of facial nerve function has been developed in order to avoid this complication. OBJECTIVE: Which methods for intraoperative monitoring have been developed? Which methods are in use today and what can they achieve in modern vestibular schwannoma surgery? MATERIAL AND METHODS: This article provides an evaluation and summary of the literature, as well as a discussion of the methods and their ability to achieve the goals of intraoperative monitoring. RESULTS: Intraoperative functional monitoring aims to identify and map the facial nerve in the surgical field during surgery. It also aims to identify potentially damaging events and allow for intraoperative prognosis of functional outcome. Available methods are direct electrical stimulation, free-running electromyogram (EMG), facial nerve evoked potentials, and processed EMG. CONCLUSION: Identification and mapping of the facial nerve in the surgical field can be reliably achieved by direct electrical stimulation; potentially dangerous events can be identified in real time by the free-running EMG and the processed EMG, and almost in real time by facial nerve evoked potentials. Intraoperative prognostics are hampered by false-positive results with all available methods and have limited reliability.

[Intraoperative monitoring of cochlear nerve function during cerebello-pontine angle surgery]. / Intraoperatives Monitoring des N. cochlearis bei Eingriffen im Kleinhirnbrückenwinkel.

BACKGROUND: Surgical procedures in the cerebello-pontine angle (CPA), e. g. for vestibular schwannoma, have an increased risk for damage to the cochlear nerve. Consequently, hearing deterioration up to complete deafness may result with severe impact on quality of life. Methods for intraoperative monitoring of function may minimize such risks. OBJECTIVE: Review of current methods for intraoperative monitoring of the cochelar nerve and summary of new developments. MATERIALS AND METHODS: Analysis and summary of literature, discussion of new methods. RESULTS: Early auditory evoked potentials using click stimuli remain the standard method for intraoperative monitoring of cochlear nerve function. Amplitude and latency changes indicate a risk of postoperative hearing deterioration; however demonstrate only limited further differentiation of hearing quality. As novel methods, near-field recordings may allow faster feedback and auditory steady state responses potentially enable frequency specific testing. CONCLUSIONS: Intraoperative monitoring of the cochlear nerve is an integral component of CPA surgery. It enables detection of potential nerve damage and thus contributes to avoiding postoperative functional deficits. Development and implementation of novel and additional approaches may further improve its clinical value.

Oligothiophene wires: impact of torsional conformation on the electronic structure.

Charge transport in polymer- and oligomer-based semiconductor materials depends strongly on the structural ordering of the constituent molecules. Variations in molecular conformations influence the electronic structures of polymers and oligomers, and thus impact their charge-transport properties. In this study, we used Scanning Tunneling Microscopy and Spectroscopy (STM/STS) to investigate the electronic structures of different alkyl-substituted oligothiophenes displaying varied torsional conformations on the Au(111) surface. STM imaging showed that on Au(111), oligothiophenes self-assemble into chain-like structures, binding to each other via interdigitated alkyl ligands. The molecules adopted distinct planar conformations with alkyl ligands forming cis- or trans- mutual orientations. For each molecule, by using STS mapping, we identify a progression of particle-in-a-box-like states corresponding to the LUMO, LUMO+1 and LUMO+2 orbitals. Analysis of STS data revealed very similar unoccupied molecular orbital energies for different possible molecular conformations. By using density functional theory calculations, we show that the lack of variation in molecular orbital energies among the different oligothiophene conformers implies that the effect of the Au-oligothiophene interaction on molecular orbital energies is nearly identical for all studied torsional conformations. Our results suggest that cis-trans torsional disorder may not be a significant source of electronic disorder and charge carrier trapping in organic semiconductor devices based on oligothiophenes.

The PTS(Ntr) system globally regulates ATP-dependent transporters in Rhizobium leguminosarum.

Mutation of ptsP encoding EI(Ntr) of the PTS(Ntr) system in Rhizobium leguminosarum strain Rlv3841 caused a pleiotropic phenotype as observed with many bacteria. The mutant formed dry colonies and grew poorly on organic nitrogen or dicarboxylates. Most strikingly the ptsP mutant had low activity of a broad range of ATP-dependent ABC transporters. This lack of activation, which occurred post-translationally, may explain many of the pleiotropic effects. In contrast proton-coupled transport systems were not inhibited in a ptsP mutant. Regulation by PtsP also involves two copies of ptsN that code for EIIA(Ntr) , resulting in a phosphorylation cascade. As in Escherichia coli, the Rlv3841 PTS(Ntr) system also regulates K(+) homeostasis by transcriptional activation of the high-affinity ATP-dependent K(+) transporter KdpABC. This involves direct interaction of a two-component sensor regulator pair KdpDE with unphosphorylated EIIA(Ntr) . Critically, ptsP mutants, which cannot phosphorylate PtsN1 or PtsN2, had a fully activated KdpABC transporter. This is the opposite pattern from that observed with ABC transporters which apparently require phosphorylation of PtsN. These results suggest that ATP-dependent transport might be regulated via PTS(Ntr) responding to the cellular energy charge. ABC transport may be inactivated at low energy charge, conserving ATP for essential processes including K(+) homeostasis.

The current management of lumbar spondylolisthesis.

Lumbar spondylolisthesis can lead to disabling low back pain and neurological deficits. This review details the clinical history, neurological examination, clinical presentation, imaging modalities, and current management standards for lumbar spondylolisthesis. Based on the available clinical trials, there is evidence that, compared with nonsurgical care, the surgical treatment of symptomatic spondylolisthesis offers a significant clinical benefit in the presence of progressive neurological deficits; cauda equina syndrome; failure of an adequate response to conservative therapy: radiographic instability with neurological symptoms; radiographic progression of subluxation to greater than grade II; symptomatic grades III, II, or spondyloptosis; and unremitting pain that affects the quality of life. Optimizing the diagnostic paths and surgical indications and standardizing both the surgical procedures as well as the outcome measurements with validated instruments should assist the spine care community in acquiring data that are essential for providing the best evidence-based treatment while reducing or eliminating procedures that lack evidence of either efficacy or value.

A-trains for intraoperative monitoring in patients with recurrent vestibular schwannoma.

BACKGROUND: Second surgery of recurrent vestibular schwannoma (VS) after previous surgery, stereotactic radiosurgery (SR) or fractionated radiotherapy (FR) carries an increased risk for deterioration of facial nerve function, e.g., due to adhesions, underlining the need for intraoperative monitoring. Facial "Atrain" EMG activity ("traintime") correlates with the degree of postoperative facial palsy. Studies investigating A-trains in VS patients with previous surgery, SR or FR are missing. We therefore investigated the value of A-train monitoring in patients undergoing second surgery for VS. METHOD: Intraoperative EMG data from patients who underwent second surgery for VS after previous surgery, SR and/or FR at our institution between 2006 and 2012 were retrospectively analyzed. Ten patients were selected (5 male): Seven had previous SR/RT and MS, three previous surgery only. Traintime values and distribution was compared to published thresholds and to 77 patients who underwent first surgery for VS during the same time period. RESULTS: A-trains were recorded early after opening of the dura, before facial nerve preparation. Mean traintime was 46.9 s (18.51 s ­ 80.82 s) in patients with previous SR/RT. In patients with previous MS only, traintime was 0.06 s, 0.99 s and 22.46 s. Compared to the literature, traintime was higher than expected in six patients (four with previous SR/RT, two without), respectively seven compared to the 77 patients with first surgery (5 SR/RT). Seven patients with previous SR/RT and none with previous surgery showed diffuse A-train distributions without significant percentages in single channels, compared to 60 of 77 patients with first surgery (p <0.02). CONCLUSIONS: Especially SR/RT, but also previous surgery seems to induce changes in the facial nerve leading to hyperexcitability and exceedingly high traintime values. Based on these findings, A-train monitoring in this specific patient group should be interpreted with caution.

Mutation of GOGAT prevents pea bacteroid formation and N2 fixation by globally downregulating transport of organic nitrogen sources.

Mutation of gltB (encoding glutamate oxoglutarate amidotransferase or GOGAT) in RU2307 increased the intracellular Gln:Glu ratio and inhibited amino acid transport via Aap and Bra. The mechanism probably involves global post-translational inhibition independent of Ntr. Transport was separately restored by increased gene expression of Aap or heterologous transporters. Likewise, second site suppressor mutations in the RNA chaperone Hfq elevated transport by Aap and Bra by increasing mRNA levels. Microarrays showed Hfq regulates 34 ABC transporter genes, including aap, bra and opp. The genes coding for integral membrane proteins and ABC subunits aapQMP braDEFGC were more strongly elevated in the hfq mutants than solute-binding proteins (aapJ braC). aapQMP and braDEFG are immediately downstream of stem-loops, indicating Hfq attenuates downstream translation and stability of mRNA, explaining differential expression of ABC genes. RU2307 nodulated peas and bacteria grew down infection threads, but bacteroid development was arrested and N(2) was not fixed. This probably results from an inability to synthesize or transport amino acids. However, GOGAT and GOGAT/AldA double mutants carrying suppressor mutations that increased amino acid uptake fixed N(2) on pea plants. Thus de novo ammonium assimilation into amino acids is unnecessary in bacteroids demonstrating sufficient amino acids are supplied by plants.

Legumes regulate Rhizobium bacteroid development and persistence by the supply of branched-chain amino acids.

One of the largest contributions to biologically available nitrogen comes from the reduction of N(2) to ammonia by rhizobia in symbiosis with legumes. Plants supply dicarboxylic acids as a carbon source to bacteroids, and in return they receive ammonia. However, metabolic exchange must be more complex, because effective N(2) fixation by Rhizobium leguminosarum bv viciae bacteroids requires either one of two broad-specificity amino acid ABC transporters (Aap and Bra). It was proposed that amino acids cycle between plant and bacteroids, but the model was unconstrained because of the broad solute specificity of Aap and Bra. Here, we constrain the specificity of Bra and ectopically express heterologous transporters to demonstrate that branched-chain amino acid (LIV) transport is essential for effective N(2) fixation. This dependence of bacteroids on the plant for LIV is not due to their known down-regulation of glutamate synthesis, because ectopic expression of glutamate dehydrogenase did not rescue effective N(2) fixation. Instead, the effect is specific to LIV and is accompanied by a major reduction in transcription and activity of LIV biosynthetic enzymes. Bacteroids become symbiotic auxotrophs for LIV and depend on the plant for their supply. Bacteroids with aap bra null mutations are reduced in number, smaller, and have a lower DNA content than wild type. Plants control LIV supply to bacteroids, regulating their development and persistence. This makes it a critical control point for regulation of symbiosis.

Characterization of a {gamma}-aminobutyric acid transport system of Rhizobium leguminosarum bv. viciae 3841.

Spontaneous mutants of Rhizobium leguminosarum bv. viciae 3841 were isolated that grow faster than the wild type on gamma-aminobutyric acid (GABA) as the sole carbon and nitrogen source. These strains (RU1736 and RU1816) have frameshift mutations (gtsR101 and gtsR102, respectively) in a GntR-type regulator (GtsR) that result in a high rate of constitutive GABA transport. Tn5 mutagenesis and quantitative reverse transcription-PCR showed that GstR regulates expression of a large operon (pRL100242 to pRL100252) on the Sym plasmid that is required for GABA uptake. An ABC transport system, GtsABCD (for GABA transport system) (pRL100248-51), of the spermidine/putrescine family is part of this operon. GtsA is a periplasmic binding protein, GtsB and GtsC are integral membrane proteins, and GtsD is an ATP-binding subunit. Expression of gtsABCD from a lacZ promoter confirmed that it alone is responsible for high rates of GABA transport, enabling rapid growth of strain 3841 on GABA. Gts transports open-chain compounds with four or five carbon atoms with carboxyl and amino groups at, or close to, opposite termini. However, aromatic compounds with similar spacing between carboxyl and amino groups are excellent inhibitors of GABA uptake so they may also be transported. In addition to the ABC transporter, the operon contains two putative mono-oxygenases, a putative hydrolase, a putative aldehyde dehydrogenase, and a succinate semialdehyde dehydrogenase. This suggests the operon may be involved in the transport and breakdown of a more complex precursor to GABA. Gts is not expressed in pea bacteroids, and gtsB mutants are unaltered in their symbiotic phenotype, suggesting that Bra is the only GABA transport system available for amino acid cycling.

Transcriptomic analysis of Rhizobium leguminosarum biovar viciae in symbiosis with host plants Pisum sativum and Vicia cracca.

Rhizobium leguminosarum bv. viciae forms nitrogen-fixing nodules on several legumes, including pea (Pisum sativum) and vetch (Vicia cracca), and has been widely used as a model to study nodule biochemistry. To understand the complex biochemical and developmental changes undergone by R. leguminosarum bv. viciae during bacteroid development, microarray experiments were first performed with cultured bacteria grown on a variety of carbon substrates (glucose, pyruvate, succinate, inositol, acetate, and acetoacetate) and then compared to bacteroids. Bacteroid metabolism is essentially that of dicarboxylate-grown cells (i.e., induction of dicarboxylate transport, gluconeogenesis and alanine synthesis, and repression of sugar utilization). The decarboxylating arm of the tricarboxylic acid cycle is highly induced, as is gamma-aminobutyrate metabolism, particularly in bacteroids from early (7-day) nodules. To investigate bacteroid development, gene expression in bacteroids was analyzed at 7, 15, and 21 days postinoculation of peas. This revealed that bacterial rRNA isolated from pea, but not vetch, is extensively processed in mature bacteroids. In early development (7 days), there were large changes in the expression of regulators, exported and cell surface molecules, multidrug exporters, and heat and cold shock proteins. fix genes were induced early but continued to increase in mature bacteroids, while nif genes were induced strongly in older bacteroids. Mutation of 37 genes that were strongly upregulated in mature bacteroids revealed that none were essential for nitrogen fixation. However, screening of 3,072 mini-Tn5 mutants on peas revealed previously uncharacterized genes essential for nitrogen fixation. These encoded a potential magnesium transporter, an AAA domain protein, and proteins involved in cytochrome synthesis.

Characterisation of Phaseolus symbionts isolated from Mediterranean soils and analysis of genetic factors related to pH tolerance.

The ultimate objective of PhIMED, in which two European (Germany, Italy) and two Mediterranean (Morocco, Egypt) countries collaborate, is to improve the cultivation of French bean (Phaseolus vulgaris) under arid and semi-arid conditions by analysing and enhancing stress tolerance of the nitrogen fixing rhizobial microsymbionts. Rhizobial strains nodulating P. vulgaris (RP strains) isolated from areas in Morocco frequently subjected to drought were analysed for their salt and pH tolerance and their phylogenetic relationship. Strain RP163, exhibiting high nodulation efficiency and a broad pH tolerance was mutagenised by Tn5 and mutants unable to grow on extreme pH media were isolated. Some of the mutants affected in low pH tolerance were found to be mutated in genes related to cobalmin biosynthesis and in succinate dehydrogenase (sdhA). In a parallel approach, promoters and genes inducible under extreme pH values were identified in Rhizobium leguminosarum bv. viciae VF39, among them gabT, which encodes the GABA transaminase and which is induced under acidic conditions. The same gene is present and similarly regulated in RP163. The actSR gene region was cloned from VF39, sequenced and mutants generated in this region were found to be impaired in growth at low pH, but also under neutral conditions. The Agrobacterium rhizogenes 'promintron' promoter, reported to be activated in stationary phase, was found to be also strongly induced under acidic conditions in rhizobia and it is currently being characterised to construct a system allowing the expression of stress tolerance genes in bacteroids and free-living bacteria.

Epidermoid tumor of the cerebellopontine angle presenting with selective sudden hearing loss. Intraoperative evidence of a pearl tumor infiltrating and compressing the cochlear nerve.

Epidermoid tumors of the cerebellopontine angle are associated with a variety of symptoms, usually attributed to compression and displacement of involved cranial nerves. The authors present a case of a large epidermoid tumor in the left cerebellopontine angle with sudden hearing loss and tinnitus. The intraoperative finding of migration of two tumor pearls into the cochlear nerve was the origin of the clinical sign. The patient improved remarkably after removal of the tumor. This case demonstrates the mechanism for selective hearing loss associated with the large cerebellopontine angle.

Prophylactic intravenous nimodipine treatment in skull base surgery: pharmacokinetic aspects.

BACKGROUND: Nimodipine is primarily used in subarachnoid hemorrhage (SAH). Clinical trials revealed also a beneficial effect of prophylactic nimodipine treatment on cranial nerve functions following vestibular schwannoma surgery. OBJECTIVE: The unknown pharmacokinetics of prophylactically administered nimodipine were investigated. METHODS: Samples were taken from 27 patients with skull base lesions. Prophylactic intravenous nimodipine infusion was started 5.8-25.8 h (mean 17.9 h) before surgery. Nimodipine concentrations were determined in serum (intra- and postoperatively), cerebrospinal fluid (CSF) (intraoperatively), and tissue samples. RESULTS: Wide interindividual differences were observed. Mean concentrations for nimodipine were 46.9 ng/ml (SD: 6.4; min. 4.1 and max. 92.7 ng/ml) in intraoperative serum, 73.2 ng/ml (SD: 16.7; min. 6.6 and max. 253 ng/ml) in postoperative serum and 8.3 ng/ml (SD: 1.5; min. 1.0 und max. 29.7 ng/ml) in intraoperative CSF. The correlation between intra- and postoperative serum (p=0.004, r=0.560) and between intra-operative serum and CSF concentration (p=0.003, r=0.567) were statistically significant. Furthermore the correlation between intraoperative serum concentration and concentrations collected from vestibular nerves was high (r=0.711), but not statistically significant (p=0.178). CONCLUSIONS: Interindividually, continously administered intravenous nimodipine produces considerably variable serum levels. Controls of nimodipine serum concentrations may be useful to optimize nimodipine medication in skull base surgery and in the management of SAH. The serum nimodipine level is a useful marker for CSF and intracranial nerve tissue concentrations of nimodipine.

Practice in the perioperative prevention of deep vein thrombosis in german neurosurgical departments: is there a trend towards homogenization?

OBJECTIVE: There was no consensus on the most suitable perioperative prophylaxis of deep vein thrombosis (DVT) in neurosurgical patients. The aim of this work was to review the current practice and search for a standard protocol in the prophylaxis of DVT. METHODS AND MATERIAL: Questionnaires addressing the routine prophylaxis of perioperative DVT for 4 groups of neurosurgical procedures and the estimation of risks and benefits of perioperative heparin (unfractionated and/or low-molecular-weight) administration were sent to 130 neurosurgical departments in Germany. RESULTS: 103 of 130 questionnaires were returned and suitable for analysis. The use of heparin (unfractionated and/or low-molecular-weight) is common, with some variation depending on the type of operation (83.5-99%). In spinal procedures, heparin administration is commonly started early, i. e., between the preoperative and first postoperative day (90.3-97.1%). This differs in intracranial procedures. In most neurosurgical departments heparin administration is stopped at the day of discharge (69.6-77.4% depending on procedure). Enoxaparin is the most commonly used heparin. In spinal as well as in cranial procedures, thrombosis risk reduction is unanimously assumed to be lesser the later administration starts. The estimation of the risks related to heparin injection are considered to be higher in cranial than in spinal operation in the early postoperative period. Most departments use antithrombotic stockings (ATS) irrespective of the type of surgery. However, 11% never use ATS. CONCLUSIONS: In spinal surgery, a trend towards homogenization is observed with the early use of heparin. In intracranial procedures, practice is more heterogenous. The heterogeneity is due to the fact that the data available in the literature does not allow for the identification of an optimal protocol.

Does electrode placement influence quality of intraoperative monitoring in vestibular schwannoma surgery?

OBJECT: Continuous recording of electromyographic signals (EMG) is a standard method for intraoperative monitoring of facial nerve function in cerebello-pontine angle surgery. Subcutaneous needle electrodes in the facial muscles are used in different setups. The goal of this study was to compare two commonly used electrode setups concering sensitivity for pathological EMG activity. PATIENTS AND METHODS: A group of 10 patients undergoing vestibular schwannoma surgery were examined. Continuous EMG from facial muscles was recorded using needle electrodes in setups according to Kartush or Møller, with narrow or wide interelectrode distances, respectively. Quantity of pathological A-train activity and signal-to-noise ratios were compared between setups. RESULTS: A-train activity was seen in all patients. On average, 37% of A-train activity was seen in the Kartush setup alone, 4% in Møller setups alone and 59% in both setups synchronously (p<0.05; ratio of median train time--Kartush:Møller 3:2). The wide interelectrode distance of the Møller setup was found to be significantly more susceptible to artefacts, especially to low frequency and power line noise. Artefacts were the main reason for the Møller setup to fail detecting A-train activity. CONCLUSIONS: For continuous intraoperative monitoring of facial nerve function, narrow interelectrode distance should be used.

Contrast enhancement and histopathological findings in vestibular schwannoma.

Changes of contrast uptake are considered to indicate the efficacy of therapy in irradiated vestibular schwannomas. We present a case of a large vestibular schwannoma with heterogeneous contrast uptake on MRI. Using neuronavigation, histological samples were obtained during surgery from an area with homogeneous contrast uptake and from a central tumor portion without contrast enhancement on MRI. Intraoperative investigation found no evidence of necrotic tumor, and histopathological examination revealed an active tumor in both sections, with no central necrosis. This finding illustrates the surgical experience that " necrotic tumor areas " on MRI may not be consistent with intraoperative findings. Lack of contrast uptake in previously irradiated schwannomas may not be indicative of effective radiotherapy.

Degradation pathway of bisphenol A: does ipso substitution apply to phenols containing a quaternary alpha-carbon structure in the para position?

The degradation of bisphenol A and nonylphenol involves the unusual rearrangement of stable carbon-carbon bonds. Some nonylphenol isomers and bisphenol A possess a quaternary alpha-carbon atom as a common structural feature. The degradation of nonylphenol in Sphingomonas sp. strain TTNP3 occurs via a type II ipso substitution with the presence of a quaternary alpha-carbon as a prerequisite. We report here a new degradation pathway of bisphenol A. Consequent to the hydroxylation at position C-4, according to a type II ipso substitution mechanism, the C-C bond between the phenolic moiety and the isopropyl group of bisphenol A is broken. Besides the formation of hydroquinone and 4-(2-hydroxypropan-2-yl)phenol as the main metabolites, further compounds resulting from molecular rearrangements consistent with a carbocationic intermediate were identified. Assays with resting cells or cell extracts of Sphingomonas sp. strain TTNP3 under an (18)O(2) atmosphere were performed. One atom of (18)O(2) was present in hydroquinone, resulting from the monooxygenation of bisphenol A and nonylphenol. The monooxygenase activity was dependent on both NADPH and flavin adenine dinucleotide. Various cytochrome P450 inhibitors had identical inhibition effects on the conversion of both xenobiotics. Using a mutant of Sphingomonas sp. strain TTNP3, which is defective for growth on nonylphenol, we demonstrated that the reaction is catalyzed by the same enzymatic system. In conclusion, the degradation of bisphenol A and nonylphenol is initiated by the same monooxygenase, which may also lead to ipso substitution in other xenobiotics containing phenol with a quaternary alpha-carbon.

The degradation of alpha-quaternary nonylphenol isomers by Sphingomonas sp. strain TTNP3 involves a type II ipso-substitution mechanism.

The degradation of radiolabeled 4(3',5'-dimethyl-3'-heptyl)-phenol [nonylphenol (NP)] was tested with resting cells of Sphingomonas sp. strain TTNP3. Concomitantly to the degradation of NP, a metabolite identified as hydroquinone transiently accumulated and short-chain organic acids were then produced at the expense of hydroquinone. Two other radiolabeled isomers of NP, 4(2',6'-dimethyl-2'-heptyl)-phenol and 4(3',6'-dimethyl-3'-heptyl)-phenol, were synthesized. In parallel experiments, the 4(2',6'-dimethyl-2'-heptyl)-phenol was degraded more slowly than the other isomers of NP by strain TTNP3, possibly because of effects of the side-chain structure on the kinetics of degradation. Alkylbenzenediol and alkoxyphenol derivatives identified as metabolites during previous studies were synthesized and tested as substrates. The derivatives were not degraded, which indicated that the mineralization of NP does not proceed via alkoxyphenol as the principal intermediate. The results obtained led to the elucidation of the degradation pathway of NP isomers with a quaternary alpha-carbon. The proposed mechanism is a type II ipso substitution, leading to hydroquinone and nonanol as the main metabolites and to the dead-end metabolites alkylbenzenediol or alkoxyphenol, depending on the substitution at the alpha-carbon of the carbocationic intermediate formed.