The Impact of Magnetoencephalography-Directed Stereo-Electroencephalography Depth Electrode Implantation on Seizure Control Outcome in Children.

Introduction The use of magnetoencephalography (MEG) in localizing epileptic foci and directing surgical treatment of medically refractory epilepsy is well established in clinical practice; however, it has not yet been incorporated into the routine planning of stereo-electroencephalography (EEG) (SEEG) depth electrode trajectories during invasive intracranial evaluation for epileptic foci localization. In this study, we assess the impact of MEG-directed SEEG on seizure outcomes in a pediatric cohort. Methods A retrospective analysis was performed on a single-institution cohort of pediatric patients with medically refractory epilepsy who underwent epilepsy surgery. The primary endpoint was the reduction in seizure burden as determined by dichotomized Engel scores (favorable outcome: Engel scores I and II; poor outcome: Engel scores III and IV). Results Thirty-seven patients met the inclusion criteria (24 males and 13 females). The median age at seizure onset was three years, the median age at surgery was 14.1 years, and the median follow-up length was 30.8 months. Concordance was noted in 7/10 (70%) patients who received MEG-directed SEEG. Good clinical outcomes were achieved in 70% of MEG-directed SEEG patients, compared to 59.4% in their counterparts; however, this difference was not statistically significant (p=0.72). We noted no statistically significant association between sex, disease laterality, or age at surgery and good clinical outcomes. Conclusions Patients who underwent MEG-directed SEEG had favorable clinical outcomes, which demonstrated the practicability of this technique for determining SEEG electrode placement. Although no significant difference in clinical outcomes was obtained between the two groups, this may have been due to low statistical power. Future prospective, multi-institutional investigations to assess the benefit of MEG-directed SEEG are warranted.

Potential benefits from deeply inserted cochlear implant electrodes.

OBJECTIVES: This review examines evidence for potential benefits of using cochlear implant electrodes that extend into the apical regions of the cochlea. Most cochlear implant systems use electrode arrays that extend 1 to 1.5 turns from the basal cochleostomy, but one manufacturer (MED-EL GmbH) uses an electrode array that is considerably longer. The fundamental rationale for using electrodes extending toward the apex of the cochlea is to provide additional low-pitched auditory percepts and thereby increase the spectral information available to the user. Several experimental long arrays have also been produced by other manufacturers to assess potential benefits of this approach. DESIGN: In addition to assessing the effects of deeply inserted electrodes on performance, this review examines several underlying and associated issues, including cochlear anatomy, electrode design, surgical considerations (including insertion trauma), and pitch scaling trials. Where possible, the aim is to draw conclusions regarding the potential from apical electrodes in general, rather than relating to the performance of specific and current devices. RESULTS: Imaging studies indicate that currently available electrode arrays rarely extend more than two turns into the cochlea, the mean insertion angle for full insertions of the MED-EL electrodes being about 630°. This is considerably shorter than the total length of the cochlea and more closely approximates the length of the spiral ganglion. Anatomical considerations, and some modelling studies, suggest that fabrication of even longer electrodes is unlikely to provide additional spectral information. The issue of potential benefit from the most apical electrodes, therefore, is whether they are able to selectively stimulate discrete and tonotopically ordered neural populations near the apex of the spiral ganglion, where the ganglion cells are closely grouped. Pitch scaling studies, using the MED-EL and experimental long arrays, suggest that this is achieved in many cases, but that a significant number of individuals show evidence of pitch confusions or reversals among the most apical electrodes, presumably reducing potential performance benefit and presenting challenges for processor programming. CONCLUSIONS: Benefits in terms of speech recognition and other performance measures are less clear. Several studies have indicated that deactivation of apical electrodes results in poorer speech recognition performance, but these have been mostly acute studies where the subjects have been accustomed to the full complement of electrodes, thus making interpretation difficult. Some chronic studies have suggested that apical electrodes do provide additional performance benefit, but others have shown performance improvement after deactivating some of the apical electrodes. Whether or not deeply inserted electrodes can offer performance benefits, there is evidence that currently available designs tend to produce more intracochlear trauma than shorter arrays, in terms of loss of residual acoustic hearing and reduction of the neural substrate. This may have important long-term consequences for the user. Furthermore, as it is possible that subjects with better low-frequency residual hearing are more likely to benefit from the inclusion of apical electrodes, there may be a potential clinical dilemma as the same subjects are those most likely to benefit from bimodal electroacoustic stimulation, requiring a relatively shallow insertion.

Automated flow control of a multi-lane swimming chamber for small fishes indicates species-specific sensitivity to experimental protocols.

In fishes, swimming performance is considered an important metric to measure fitness, dispersal and migratory abilities. The swimming performance of individual larval fishes is often integrated into models to make inferences on how environmental parameters affect population-level dynamics (e.g. connectivity). However, little information exists regarding how experimental protocols affect the swimming performance of marine fish larvae. In addition, the technical setups used to measure larval fish swimming performance often lack automation and accurate control of water quality parameters and flow velocity. In this study, we automated the control of multi-lane swimming chambers for small fishes by developing an open-source algorithm. This automation allowed us to execute repeatable flow scenarios and reduce operator interference and inaccuracies in flow velocity typically associated with manual control. Furthermore, we made structural modifications to a prior design to reduce the areas of lower flow velocity. We then validated the flow dynamics of the new chambers using computational fluid dynamics and particle-tracking software. The algorithm provided an accurate alignment between the set and measured flow velocities and we used it to test whether faster critical swimming speed (U crit) protocols (i.e. shorter time intervals and higher velocity increments) would increase U crit of early life stages of two tropical fish species [4-10-mm standard length (SL)]. The U crit of barramundi (Lates calcarifer) and cinnamon anemonefish (Amphiprion melanopus) increased linearly with fish length, but in cinnamon anemonefish, U crit started to decrease upon metamorphosis. Swimming protocols using longer time intervals (more than 2.5 times increase) negatively affected U crit in cinnamon anemonefish but not in barramundi. These species-specific differences in swimming performance highlight the importance of testing suitable U crit protocols prior to experimentation. The automated control of flow velocity will create more accurate and repeatable data on swimming performance of larval fishes. Integrating refined measurements into individual-based models will support future research on the effects of environmental change.

Evaluation of simplified programs using the MED-EL C40+ cochlear implant.

The present study evaluated the benefit possible from a cochlear implant (CI) using a simplified map (with a set of default parameters), rather than the conventional approach of producing a 'customized map' from electrode-specific psychophysical measures. Young children are sometimes initially provided with such maps and the aim was to gain an insight into what level of benefit they might provide. Maps with upper stimulation levels set equally across the array (i.e. 'flat' maps) were compared with normal 'customized' maps in established adult users of the MED-EL C40+ device. Speech discrimination was significantly poorer for the flat maps overall (mean of 72.7% for customized map, and 60.5% for flat map) and loudness balance estimates showed a range of degrees of imbalance. These results suggest that flat maps may provide paediatric CI users with useful levels of performance when psychophysical or objective measures cannot be obtained. The poorer performance with the flat map suggests that customized maps should be fit as soon as possible to provide paediatric patients with the maximum benefit of the CI device.

Potential insertion complications with cochlear implant electrodes.

Objectives: The aim of this discussion paper and literature review was to estimate the incidence of a variety of complications associated with the surgical placement of cochlear implant (CI) electrode arrays and to discuss the implications and management of sub-optimal electrode placement. Results: A review of the peer-reviewed literature suggests that the incidence of incomplete electrode insertion and kinking is more prevalent in straight arrays and not more than about 2% in CI recipients with normal cochlear anatomy/patency. Incidence of tip fold-over is greater with perimodiolar arrays but also occurs with straight arrays and is typically less than 5%. Conversely, electrode migration is more common with straight arrays, and high rates (up to 46%) have been reported in some studies. Scalar translocations have also been reported for both perimodiolar and straight arrays. Higher rates have been reported for stylet-based perimodiolar electrodes inserted via cochleostomy (up to 56%), but with much lower rates (<10%) with both sheath-based perimodiolar arrays and lateral wall arrays. Electrode positioning complications represent a significant proportion of perioperative CI complications and compromise the level of benefit from the device. Careful surgical planning and appropriate pre- and intraoperative imaging can reduce the likelihood and impact of electrode positioning complications. There is also evidence that newer array designs are less prone to certain complications, particularly scalar translocation. Conclusions: It is important that implanting surgeons are aware of the impact of sub-optimal electrode placement and the steps that can be taken to avoid, identify and manage such complications.

Controlled comparative clinical trial of hearing benefit outcomes for users of the Cochlear™ Nucleus® 7 Sound Processor with mobile connectivity.

OBJECTIVES: To assess subjective benefits and objective speech recognition performance following a take-home trial with the new Cochlear™ Nucleus® 7 Sound Processor (SP), in experienced users of compatible cochlear implants from Cochlear Limited. METHODS: A total of 37 adult participants were fitted with the Nucleus 7 SP and used the device for up to one year. Baseline speech recognition was assessed at the initial fitting session, using each participant's own SP, and Client Oriented Scale of Improvement (COSI) goals were identified. Speech recognition was measured after 3 months of device use and outcomes of the COSI and a non-validated Processor Comparison Questionnaire (PCQ) were collected. After 11 months, a subset of subjects were tested on speech recognition delivered via direct wireless streaming from an Apple® smartphone to the SP and compatible hearing aid on the opposite side (if worn). RESULTS: The COSI and PCQ instruments both indicated significant improvement in perceived subjective benefits in comparison to the participants' previous SPs. Direct streaming via an Apple mobile phone showed improvements when compared with the acoustic alone condition. Standard speech recognition in quiet and noise was equivalent to that obtained using a previous generation SP which uses the same basic processing as the Nucleus 7 Sound Processor. CONCLUSIONS: The incremental refinements provided by the Nucleus 7 Sound Processor provide real-world benefits in key areas such as upgraded wireless connectivity. The COSI proved to be an effective tool for individualized assessment of specific benefits that may not be addressed by more standardized instruments.

Amalgam dental fillings and hearing loss.

In this study we investigated the effects of amalgam dental fillings on auditory thresholds. Participants (n=39) were non-smoking women age 40 to 45. Regression and correlation analyses were performed between auditory thresholds, measured from 0.25 to 16 kHz, and the number/surface area of dental fillings, using the ASHA criteria for ototoxic change as a reference for comparison. No significant correlation (p>0.05) was found between composite (non-amalgam) filling or drilling data and auditory thresholds. However, there was a significant positive linear correlation between amalgam filling data and auditory thresholds at 8, 11.2, 12.5, 14, and 16 kHz. The strongest association (r=0.587, n=39, p<.001, r(2)=0.345) was at 14 kHz, where each additional amalgam filling was associated with a 2.4 dB decline in hearing threshold (95% confidence interval [CI], 1.3-3.5 dB). The results suggest an association between more amalgam fillings and poorer thresholds at higher frequencies, which could contribute to presbyacusis in developed countries. This provides further argument for the use of amalgams to be phased out where suitable alternatives exist.

Investigations into electrically evoked stapedius reflex measures and subjective loudness percepts in the MED-EL COMBI 40+ cochlear implant.

For several years there has been interest in using objective measures to set channel-specific upper programming limits when programming the speech processor of cochlear implant users. The present study aims to add to previous reports by examining correlations between electrically evoked stapedius reflex threshold (ESRT) and a range of psychophysical loudness estimates in a group of 22 adult users of the MED-EL COMBI 40+ system. Thirteen of the 15 subjects (87%) had recordable stapedius reflexes. Psychophysical measures of threshold, maximum comfort level (MCL) and maximum acceptable loudness (MAL) were recorded. Results showed that mean ESRT was closest to the MCL using 500 ms burst ('MCL500'), with MCL50 (MCL using 50 ms burst) and MAL500 some 2dB and MAL50 3dB higher. Correlations between ESRT and the behavioural loudness judgements were highest for MCL500 (R = 0.69, p < 0.001) and slightly less for MAL500. These results confirm the ease of measuring ESRT in a clinical setting and that a high level of confidence can be placed on the use of these measures for setting processor maps in the absence of behavioural data.

Potential benefits from cochlear implantation of children with unilateral hearing loss.

OBJECTIVES/METHODS: The aim of this discussion paper is to review several issues relevant to the viability of cochlear implantation of children with severe-profound unilateral hearing loss (UHL) and to discuss to what extent published findings on these issues can predict likely benefits from implantation in this population. RESULTS: Several key issues are apparent from the recent literature: (i) UHL results in significant educational and psycho-social difficulties, but these are not universal in pre-lingual cases and may not be apparent for several years after birth, (ii) conventional treatments (contralateral routing of signal aids or bone-anchored hearing aids) provide limited benefit in the majority of sensorineural cases, (iii) early published outcomes from implantation of a limited number of children with acquired UHL suggest benefits similar to those observed in postlingually deafened adults, (iv) unilateral auditory deprivation results in poorer outcomes from delayed implantation of children with congenital losses, and (v) a large proportion of cases of severe-profound sensorineural UHL are associated with structural abnormalities of the cochlea or VIII nerve, such that not all children with UHL may be suitable for cochlear implantation. CONCLUSIONS: Children with acquired UHL are likely to gain similar positive benefits from cochlear implantation as those recently reported in adults (improved localization and better speech understanding in specific noise conditions). However, implantation of children with prelingual UHL is currently problematic as the impact of UHL may not become apparent until the child enters full-time education, by which time outcomes from cochlear implantation may be sub-optimal due to auditory deprivation. Development of appropriate candidacy criteria is important but challenging as criteria may need to be based on real-world hearing difficulties as well as audiological measures.

Rapid monitoring of recombinant protein products: a comparison of current technologies.

Specific measurement of recombinant protein titer in a complex environment during industrial bioprocessing has traditionally relied on labor-intensive and time-consuming immunoassays. In recent years, however, developments in analytical technology have resulted in improved methods for protein product monitoring during bioprocessing. The choice of product-monitoring technology for a particular bioprocess will depend on a variety of assay factors and instrument-specific factors. In this article, we have compiled an overview of the advantages and disadvantages of the most commonly used technologies used: electrochemiluminescence, optical biosensors, rapid chromatography and nephelometry. The advantages of each technology for measuring both small and large recombinant therapeutic proteins are compared with a conventional enzyme-linked immunosorbent assay (ELISA) technique.

Childhood otitis media and electrically elicited stapedius reflexes in adult cochlear implantees.

BACKGROUND: Electric stapedius reflex thresholds are helpful in programming cochlear implants, but only approximately two-thirds of patients have identifiable reflexes. HYPOTHESIS: Childhood otitis media correlates with absent stapedius reflexes or with high electric stimulation needed to elicit a reflex in cochlear implantees. STUDY POPULATION: Twenty-five adults with acquired hearing loss who underwent implantation with the MED-EL COMBI 40+ standard electrode array. STUDY PARAMETERS: The extent of temporal bone pneumatization, an indicator of childhood otitis media, was measured from preoperative computed tomographic images. Clinical units (in microamperes) needed to elicit a contralateral stapedius reflex, or maximum stimulation tried, were recorded. RESULTS: No definite association of pneumatization volume with intensity of stimulation was observed. The null hypothesis of no association cannot be rejected. CONCLUSION: Childhood otitis media does not seem to explain absent electric stapedius reflexes and the wide range of clinical units needed for maximum comfortable loudness level. Remaining potential explanations probably include the wide range of cochlear neurons that can be electrically stimulated, and that the maximum tolerable stimulation is too low to elicit a stapedius reflex.

The use of cone-beam computed tomography to determine cochlear implant electrode position in human temporal bones.

OBJECTIVE: To assess the utility of cone-beam computed tomography (CBCT) imaging in the estimation of cochlear implant (CI) electrode position in implanted temporal bones. STUDY DESIGN: Eight fresh frozen temporal bones were mounted and oriented as for standard surgery and were implanted with Cochlear Slim-Straight (SS) or Contour Advance electrode arrays by 2 CI surgeons. The bones were then imaged using an Accuitomo F170 CBCT scanner (isometric 250 µm voxel size) and were then processed for histologic sectioning (500 µm sections). MAIN OUTCOME MEASURES: The CBCT images and the histologic micrographs (providing the "gold standard") were examined independently by several observers who assessed the scalar position (tympani or vestibuli) of each electrode in each temporal bone specimen. RESULTS: Examination of the histologic micrographs confirmed that all electrodes were positioned within the scala tympani in all 8 bones. Similar judgments were made by the observers rating the CBCT images, except that one of the 2 observers estimated some of the apical electrodes to be located in the scala vestibuli in two of the bones implanted with the SS electrode. CONCLUSION: Cone-beam CT imaging is able to provide a good indication of the scalar position of implanted electrodes, although estimation may be slightly less reliable for apical electrodes and for straight electrode designs. Additional advantages of using CBCT for this purpose are shorter acquisition time and reduction of radiation dose as compared with conventional CT.

The use of cone beam imaging to determine cochlear implant electrode position in human temporal bones.

This paper describes the outcomes of cochlear implantation in eight cadaveric temporal bones using cone-beam CT imaging and histological examination with respect to scalar position of the electrode array.

Comparison of loudness adjustments by MCL and maplaw in users of the MED-EL COMBI 40/40+ cochlear implant system.

The programming of a CI speech processor involves measurement of electrical threshold and 'most comfortable loudness' (MCL) levels on each electrode. However, when the derived 'map' is activated the resultant percept is often too loud or too soft. In this situation, adjustments of MCL settings are usually made in order to achieve a comfortable percept.The present study examined the range of volume control adjustments in 24 users of the MED-EL C40/40+ device. Volume control settings varied from 36% to 126% with a mean of 84.3% (SD = 20.4%). Additionally, the output compression function ('maplaw') was adjusted to test whether this alternative manipulation could result in a comfortable percept. It was found that this could be achieved satisfactorily, with maplaw values ranging from 10 to 2000. Clinical implications of these findings are discussed.

Validity and reliability of devices that assess body temperature during indoor exercise in the heat.

CONTEXT: When assessing exercise hyperthermia outdoors, the validity of certain commonly used body temperature measuring devices has been questioned. A controlled laboratory environment is generally less influenced by environmental factors (eg, ambient temperature, solar radiation, wind) than an outdoor setting. The validity of these temperature measuring devices in a controlled environment may be more acceptable. OBJECTIVE: To assess the validity and reliability of commonly used temperature devices compared with rectal temperature in individuals exercising in a controlled, high environmental temperature indoor setting and then resting in a cool environment. DESIGN: Time series study. SETTING: Laboratory environmental chamber (temperature = 36.4 +/- 1.2 degrees C [97.5 +/- 2.16 degrees F], relative humidity = 52%) and cool laboratory (temperature = approximately 23.3 degrees C [74.0 degrees F], relative humidity = 40%). PATIENTS OR OTHER PARTICIPANTS: Fifteen males and 10 females. INTERVENTION(S): Rectal, gastrointestinal, forehead, oral, aural, temporal, and axillary temperatures were measured with commonly used temperature devices. Temperature was measured before and 20 minutes after entering the environmental chamber, every 30 minutes during a 90-minute treadmill walk in the heat, and every 20 minutes during a 60-minute rest in mild conditions. Device validity and reliability were assessed with various statistical measures to compare the measurements using each device with rectal temperature. A device was considered invalid if the mean bias (average difference between rectal and device temperatures) was more than +/-0.27 degrees C (+/-0.50 degrees F). MAIN OUTCOME MEASURE(S): Measured temperature from each device (mean and across time). RESULTS: The following devices provided invalid estimates of rectal temperature: forehead sticker (0.29 degrees C [0.52 degrees F]), oral temperature using an inexpensive device (-1.13 degrees C [-2.03 degrees F]), temporal temperature measured according to the instruction manual (-0.87 degrees C [-1.56 degrees F]), temporal temperature using a modified technique (-0.63 degrees C [-1.13 degrees F]), oral temperature using an expensive device (-0.86 degrees C, [-1.55 degrees F]), aural temperature (-0.67 degrees C, [-1.20 degrees F]), axillary temperature using an inexpensive device (-1.25 degrees C, [-2.24 degrees F]), and axillary temperature using an expensive device (-0.94 degrees F [-1.70 degrees F]). Measurement of intestinal temperature (mean bias of -0.02 degrees C [-0.03 degrees F]) was the only device considered valid. Devices measured in succession (intestinal, forehead, temporal, and aural) showed acceptable reliability (all had a mean bias = 0.09 degrees C [0.16 degrees F] and r >or= 0.94]). CONCLUSIONS: Even during laboratory exercise in a controlled environment, devices used to measure forehead, temporal, oral, aural, and axillary body sites did not provide valid estimates of rectal temperature. Only intestinal temperature measurement met the criterion. Therefore, we recommend that rectal or intestinal temperature be used to assess hyperthermia in individuals exercising indoors in the heat.

Effects of programming threshold and maplaw settings on acoustic thresholds and speech discrimination with the MED-EL COMBI 40+ cochlear implant.

OBJECTIVES: The principal task in the programming of a cochlear implant (CI) speech processor is the setting of the electrical dynamic range (output) for each electrode, to ensure that a comfortable loudness percept is obtained for a range of input levels. This typically involves separate psychophysical measurement of electrical threshold ([theta] e) and upper tolerance levels using short current bursts generated by the fitting software. Anecdotal clinical experience and some experimental studies suggest that the measurement of [theta]e is relatively unimportant and that the setting of upper tolerance limits is more critical for processor programming. The present study aims to test this hypothesis and examines in detail how acoustic thresholds and speech recognition are affected by setting of the lower limit of the output ("Programming threshold" or "PT") to understand better the influence of this parameter and how it interacts with certain other programming parameters. DESIGN: Test programs (maps) were generated with PT set to artificially high and low values and tested on users of the MED-EL COMBI 40+ CI system. Acoustic thresholds and speech recognition scores (sentence tests) were measured for each of the test maps. Acoustic thresholds were also measured using maps with a range of output compression functions ("maplaws"). In addition, subjective reports were recorded regarding the presence of "background threshold stimulation" which is occasionally reported by CI users if PT is set to relatively high values when using the CIS strategy. RESULTS: Manipulation of PT was found to have very little effect. Setting PT to minimum produced a mean 5 dB (S.D. = 6.25) increase in acoustic thresholds, relative to thresholds with PT set normally, and had no statistically significant effect on speech recognition scores on a sentence test. On the other hand, maplaw setting was found to have a significant effect on acoustic thresholds (raised as maplaw is made more linear), which provides some theoretical explanation as to why PT has little effect when using the default maplaw of c = 500. Subjective reports of background threshold stimulation showed that most users could perceive a relatively loud auditory percept, in the absence of microphone input, when PT was set to double the behaviorally measured electrical thresholds ([theta]e), but that this produced little intrusion when microphone input was present. CONCLUSIONS: The results of these investigations have direct clinical relevance, showing that setting of PT is indeed relatively unimportant in terms of speech discrimination, but that it is worth ensuring that PT is not set excessively high, as this can produce distracting background stimulation. Indeed, it may even be set to minimum values without deleterious effect.