Percutaneous Threshold of Facial Nerve Stimulation Predicts Facial Canal Dehiscence.

Iatrogenic facial nerve (FN) injury is one of the most feared complications of otologic surgery. Dehiscence of the bony covering of the FN within the temporal bone increases FN vulnerability to accidental injury. High-resolution computed tomography (HRCT) of the temporal bone is used preoperatively to assess middle ear and mastoid anatomy; however, it is unreliable for detecting facial canal dehiscence. In this study, our aim was to determine if preoperative percutaneous FN stimulation could predict middle ear facial canal dehiscence. Between January 2015 and February 2017, we performed preoperative HRCT and percutaneous FN stimulation on adult patients who underwent otologic surgery at our institution. Stimulation was performed with a monopolar probe placed on the skin over the stylomastoid foramen. Electrical stimuli ranged from 0 to 40 milliamperes (mA). Recordings were made from ipsilateral facial muscles. Dependent variables included threshold to compound muscle action potential (CMAP), threshold to maximum amplitude of CMAP, and maximum amplitude of CMAP for each muscle. A retrospective chart review was performed. Seventy patients met inclusion criteria. Of the 24 with an intraoperatively confirmed dehiscence, 10 were identified preoperatively by the attending surgeon on HRCT. Averages of the lowest recorded threshold to CMAP (5.1mA v. 9.1mA), and an average of the threshold to CMAP (8.9 mA. 11.8 mA) of dehiscent versus non-dehiscent nerves were significantly different (p < .05). In conclusion, percutaneous FN stimulation is a simple and cost-effective tool that can give the surgeon important preoperative information about FN anatomy.

Practice guidelines for the supervising professional: intraoperative neurophysiological monitoring.

The American Society of Neurophysiological Monitoring (ASNM) was founded in 1989 as the American Society of Evoked Potential Monitoring. From the beginning, the Society has been made up of physicians, doctoral degree holders, Technologists, and all those interested in furthering the profession. The Society changed its name to the ASNM and held its first Annual Meeting in 1990. It remains the largest worldwide organization dedicated solely to the scientifically-based advancement of intraoperative neurophysiology. The primary goal of the ASNM is to assure the quality of patient care during procedures monitoring the nervous system. This goal is accomplished primarily through programs in education, advocacy of basic and clinical research, and publication of guidelines, among other endeavors. The ASNM is committed to the development of medically sound and clinically relevant guidelines for the performance of intraoperative neurophysiology. Guidelines are formulated based on exhaustive literature review, recruitment of expert opinion, and broad consensus among ASNM membership. Input is likewise sought from sister societies and related constituencies. Adherence to a literature-based, formalized process characterizes the construction of all ASNM guidelines. The guidelines covering the Professional Practice of intraoperative neurophysiological monitoring were initially published January 24th, 2013, and subsequently that document has undergone review and revision to accommodate broad inter- and intra-societal feedback. This current version of the ASNM Professional Practice Guideline was fully approved for publication according to ASNM bylaws on February 22nd, 2018, and thus overwrites and supersedes the initial guideline.

Use of motor evoked potentials during lateral lumbar interbody fusion reduces postoperative deficits.

BACKGROUND CONTEXT: Intraoperative neurophysiological monitoring (IONM) has gained rather widespread acceptance as a method to mitigate risk to the lumbar plexus during lateral lumbar interbody fusion (LLIF) surgery. The most common approach to IONM involves using only electromyography (EMG) monitoring, and the rate of postoperative deficit remains unacceptably high. Other test modalities, such as transcranial electric motor-evoked potentials (tcMEPs) and somatosensory-evoked potentials, may be more suitable for monitoring neural integrity, but they have not been widely adopted during LLIF. Recent studies have begun to examine their utility in monitoring LLIF surgery with favorable results. PURPOSE: This study aimed to evaluate the efficacy of different IONM paradigms in the prevention of iatrogenic neurologic sequelae during LLIF and to specifically evaluate the utility of including tcMEPs in an IONM strategy for LLIF surgery. STUDY DESIGN/SETTING: A non-randomized, retrospective analysis of 479 LLIF procedures at a single institution over a 4-year period was conducted. During the study epoch, three different IONM strategies were used for LLIF procedures: (1) surgeon-directed T-EMG monitoring ("SD-EMG"), (2) neurophysiologist-controlled T-EMG monitoring ("NC-EMG"), and (3) neurophysiologist-controlled T-EMG monitoring supplemented with MEP monitoring ("NC-MEP"). PATIENT SAMPLE: The patient population comprised 254 men (53.5%) and 221 women (46.5%). Patient age ranged from a minimum of 21 years to a maximum of 89 years, with a mean of 56.6 years. OUTCOME MEASURES: Physician-documented physiological measures included manual muscle test grading of hip-flexion, hip-adduction, or knee-extension, as well as hypo- or hyperesthesia of the groin or anterolateral thigh on the surgical side. Self-reported measures included numbness or tingling in the groin or anterolateral thigh on the surgical side. METHODS: Patient progress notes were reviewed from the postoperative period up to 12 months after surgery. The rates of postoperative sensory-motor deficit consistent with lumbar plexopathy or peripheral nerve palsy on the surgical side were compared between the three cohorts. RESULTS: Using the dependent measure of neurologic deficit, whether motor or sensory, patients with NC-MEP monitoring had the lowest rate of immediate postoperative deficit (22.3%) compared with NC-EMG monitoring (37.1%) and SD-EMG monitoring (40.4%). This result extended to sensory deficits consistent with lumbar plexopathy (pure motor deficits being excluded); patients with NC-MEP monitoring had the lowest rate (20.5%) compared with NC-EMG monitoring (34.3%) and SD-EMG monitoring (36.9%). Additionally, evaluation of postoperative motor deficits consistent with peripheral nerve palsy (pure sensory deficits being excluded) revealed that the NC-MEP group had the lowest rate (5.7%) of motor deficit compared with the SD-EMG (17.0%) and NC-EMG (17.1%) cohorts. Finally, when assessing only those patients whose last follow-up was greater than or equal to 12 months (n=251), the rate of unresolved motor deficits was significantly lower in the NC-MEP group (0.9%) compared with NC-EMG (6.9%) and SD-EMG (11.0%). A comparison of the NC-MEP versus NC-EMG and SD-EMG groups, both independently and combined, was statistically significant (>95% confidence level) for all analyses. CONCLUSIONS: The results of the present study indicate that preservation of tcMEPs from the adductor longus, quadriceps, and tibialis anterior muscles are of paramount importance for limiting iatrogenic sensory and motor injuries during LLIF surgery. In this regard, the inclusion of tcMEPs serves to compliment EMG and allows for the periodic, functional assessment of at-risk nerves during these procedures. Thus, tcMEPs appear to be the most effective modality for the prevention of both transient and permanent neurologic injury during LLIF surgery. We propose that the standard paradigm for protecting the nervous system during LLIF be adapted to include tcMEPs.

Intraoperative Neurophysiological Monitoring for Endoscopic Endonasal Approaches to the Skull Base: A Technical Guide.

Intraoperative neurophysiological monitoring during endoscopic, endonasal approaches to the skull base is both feasible and safe. Numerous reports have recently emerged from the literature evaluating the efficacy of different neuromonitoring tests during endonasal procedures, making them relatively well-studied. The authors report on a comprehensive, multimodality approach to monitoring the functional integrity of at risk nervous system structures, including the cerebral cortex, brainstem, cranial nerves, corticospinal tract, corticobulbar tract, and the thalamocortical somatosensory system during endonasal surgery of the skull base. The modalities employed include electroencephalography, somatosensory evoked potentials, free-running and electrically triggered electromyography, transcranial electric motor evoked potentials, and auditory evoked potentials. Methodological considerations as well as benefits and limitations are discussed. The authors argue that, while individual modalities have their limitations, multimodality neuromonitoring provides a real-time, comprehensive assessment of nervous system function and allows for safer, more aggressive management of skull base tumors via the endonasal route.

Use of the Cultex® Radial Flow System as an in vitro exposure method to assess acute pulmonary toxicity of fine dusts and nanoparticles with special focus on the intra- and inter-laboratory reproducibility.

Exposure of the respiratory tract to airborne particles (including metal-dusts and nano-particles) is considered as a serious health hazard. For a wide range of substances basic knowledge about the toxic properties and the underlying pathomechanisms is lacking or even completely missing. Legislation demands the toxicological characterization of all chemicals placed on the market until 2018 (REACH). As toxicological in vivo data are rare with regard to acute lung toxicity or exhibit distinct limitations (e.g. inter-species differences) and legislation claims the reduction of animal experiments in general ("3R" principle), profound in vitro models have to be established and characterized to meet these requirements. In this paper we characterize a recently introduced advanced in vitro exposure system (Cultex® RFS) showing a great similarity to the physiological in vivo exposure situation for the assessment of acute pulmonary toxicity of airborne materials. Using the Cultex® RFS, human lung epithelial cells (A549 cells) were exposed to different concentrations of airborne metal dusts (nano- and microscale particles) at the air-liquid-interface (ALI). Cell viability (WST-1 assay) as a parameter of toxicity was assessed 24h after exposure with special focus on the intra- and inter-laboratory (three independent laboratories) reproducibility. Our results show the general applicability of the Cultex® RFS with regard to the requirements of the ECVAM (European Centre for the Validation of Alternative Methods) principles on test validity underlining its robustness and stability. Intra- and inter-laboratory reproducibility can be considered as sufficient if predefined quality criteria are respected. Special attention must be paid to the pure air controls that turned out to be a critical parameter for a rational interpretation of the results. Our results are encouraging and future work is planned to improve the inter-laboratory reproducibility, to consolidate the results so far and to develop a valid prediction model.

The Impacts of Water Conservation Strategies on Water Use: Four Case Studies.

We assessed impacts on water use achieved by implementation of controlled experiments relating to four water conservation strategies in four towns within the Ipswich watershed in Massachusetts. The strategies included (1) installation of weather-sensitive irrigation controller switches (WSICS) in residences and municipal athletic fields; (2) installation of rainwater harvesting systems in residences; (3) two outreach programs: (a) free home indoor water use audits and water fixture retrofit kits and (b) rebates for low-water-demand toilets and washing machines; and (4) soil amendments to improve soil moisture retention at a municipal athletic field. The goals of this study are to summarize the effectiveness of the four water conservation strategies and to introduce nonparametric statistical methods for evaluating the effectiveness of these conservation strategies in reducing water use. It was found that (1) the municipal WSICS significantly reduced water use; (2) residences with high irrigation demand were more likely than low water users to experience a substantial demand decrease when equipped with the WSICS; (3) rainwater harvesting provided substantial rainwater use, but these volumes were small relative to total domestic water use and relative to the natural fluctuations in domestic water use; (4) both the audits/retrofit and rebate programs resulted in significant water savings; and (5) a modeling approach showed potential water savings from soil amendments in ball fields.

A modular one-generation reproduction study as a flexible testing system for regulatory safety assessment.

The European Union's Registration, Evaluation and Authorisation of Chemicals (REACH) legislation mandates testing and evaluation of approximately 30,000 existing substances within a short period of time, beginning with the most widely used "high production volume" (HPV) chemicals. REACH testing requirements for the roughly 3000 HPV chemicals specify three separate tests for reproductive toxicity: two developmental toxicity studies on different animal species (OECD Test Guideline 414) and a two-generation reproduction toxicity study (OECD TG 416). These studies are highly costly in both economic and animal welfare terms. OECD TG 416 is a fertility study intended to evaluate reproductive performance of animals in the P and F1-generations following repeated exposure to a test substance. It can also be used to detect adverse effects on structural and functional development. Thus, it has conventionally been preferred to the one-generation study (OECD TG 415). Recently, the Agricultural Chemical Safety Assessment (ACSA) Technical Committee of the ILSI Health and Environmental Sciences Institute (HESI) proposed that routine two-generation studies could in most cases be replaced with an "enhanced" one-generation study (Reuter et al. [1]). The flexible design proposed by HESI-ACSA allows for the addition of one or more specialised modules, if triggered (e.g. production of a second generation or the investigation of classical developmental toxicity or developmental neuro- or immunotoxicity). Significantly, however, the HESI-ACSA proposal was designed for use in the safety assessment of pesticidal, as opposed to industrial, chemicals. Thus for the purposes of REACH, a streamlined one-generation study that also examines structural development would be the most efficient means of addressing current information requirements for HPV chemicals. This study represents a flexible testing system that can be modified to meet regulatory needs in a variety of sectors.

Alternatives to the use of animals in safety testing as required by the EU-Cosmetics Directive 2009.

Ingredients of cosmetic products are no longer allowed to be tested by animal experimentation (EU-Cosmetics Directive 76/768 EEC). For several toxicological endpoints this testing ban applies since March 11, 2009, while repeated dose toxicity tests and the test on skin sensitisation will follow on March 11, 2013. All currently available alternatives meeting the requirements of the first deadline are compiled in the following.

Goodness of fit of probability distributions for sightings as species approach extinction.

Estimating the probability that a species is extinct and the timing of extinctions is useful in biological fields ranging from paleoecology to conservation biology. Various statistical methods have been introduced to infer the time of extinction and extinction probability from a series of individual sightings. There is little evidence, however, as to which of these models provide adequate fit to actual sighting records. We use L-moment diagrams and probability plot correlation coefficient (PPCC) hypothesis tests to evaluate the goodness of fit of various probabilistic models to sighting data collected for a set of North American and Hawaiian bird populations that have either gone extinct, or are suspected of having gone extinct, during the past 150 years. For our data, the uniform, truncated exponential, and generalized Pareto models performed moderately well, but the Weibull model performed poorly. Of the acceptable models, the uniform distribution performed best based on PPCC goodness of fit comparisons and sequential Bonferroni-type tests. Further analyses using field significance tests suggest that although the uniform distribution is the best of those considered, additional work remains to evaluate the truncated exponential model more fully. The methods we present here provide a framework for evaluating subsequent models.

Eyeblink conditioning during an interstimulus interval switch in rabbits (Oryctolagus cuniculus) using picrotoxin to disrupt cerebellar cortical input to the interpositus nucleus.

The role of the cerebellar cortex in eyeblink classical conditioning remains unclear. Experimental manipulations that disrupt the normal function impair learning to various degrees, and task parameters may be important factors in determining the severity of impairment. This study examined the role of cerebellar cortex in eyeblink conditioning under conditioned stimulus?unconditioned stimulus intervals known to be optimal or nonoptimal for learning. Using infusions of picrotoxin to the interpositus nucleus of the rabbit cerebellum, the authors pharmacologically disrupted input from the cerebellar cortex while training with an interstimulus interval (ISI)-switch procedure. One group of rabbits (Oryctolagus cuniculus) was 1st trained with a 250-ms ISI (optimal) and then switched to a 750-ms ISI (nonoptimal). A 2nd group was trained in the opposite order. The most striking effect was that picrotoxin-treated rabbits initially trained with a 250-ms ISI learned comparably to controls, but those initially trained with a 750-ms ISI were severely impaired. These results suggest that functional input from cerebellar cortex becomes increasingly important for the interpositus nucleus to learn delay eyeblink conditioning as the ISI departs from an optimal interval.

Associative and non-associative blinking in classically conditioned adult rats.

Over the last several years, a growing number of investigators have begun using the rat in classical eyeblink conditioning experiments, yet relatively few parametric studies have been done to examine the nature of conditioning in this species. We report here a parametric analysis of classical eyeblink conditioning in the adult rat using two conditioned stimulus (CS) modalities (light or tone) and three interstimulus intervals (ISI; 280, 580, or 880 ms). Rats trained at the shortest ISI generated the highest percentage of conditioned eyeblink responses (CRs) by the end of training. At the two longer ISIs, rats trained with the tone CS produced unusually high CR percentages over the first few acquisition sessions, relative to rats trained with the light CS. Experiment 2 assessed non-associative blink rates in response to presentations of the light or tone, in the absence of the US, at the same ISI durations used in paired conditioning. Significantly more blinks occurred with longer than shorter duration lights or tones. A higher blink rate was also recorded at all three durations during the early tone-alone sessions. The results suggest that early in classical eyeblink conditioning, rats trained with a tone CS may emit a high number of non-associative blinks, thereby inflating the CR frequency reported at this stage of training.

Successful validation of in vitro methods in toxicology by ZEBET, the National Centre for Alternatives in Germany at the BfR (Federal Institute for Risk Assessment).

A short description of the history of the 3Rs concept is given, which was developed as the scientific concept to refine, reduce and replace animal experiments by Russel and Burch more than 40 years ago. In addition, the legal framework in Europe for developing alternatives to animal experiments is given and the current status of in vitro systems in pharmacology and toxicology is described including an update on metabolising systems. The decrease in experimental animal numbers during the past decade in Europe is illustrated by the situation in Germany and the contribution of international harmonisation of test guidelines on reducing animal numbers in regulatory testing is described. A review of the development of the principles of experimental validation is given and the 3T3 NRU in vitro phototoxicity test is used as an example for a successful validation study, which led to the acceptance of the first in vitro toxicity test for regulatory purposes by the OECD. Finally, the currently accepted alternative methods for standardisation and safety testing of drugs, biologicals and medical devices are summarised.