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When building 3D models of the subsurface, reconciling several geological and geophysical data of diverse nature, resolutions, coverage, or sensitivity, is challenging, both numerically and petrophysically. In this work, we propose a workflow for mapping selected geological features and characterise their uncertainty using a Bayesian Estimate Fusion algorithm. Different datasets such as 1D probabilistic models derived from geophysical data, drillholes and geological data are combined to produce probabilistic maps of selected geological boundaries, relying on petrophysical and geological assumptions. Leveraging large, high-quality geophysical datasets acquired in the eastern Gawler Craton in South Australia, we demonstrate the applicability of our approach with two examples: (1) we map in 3D the top of a stratigraphic unit in the cover, the Tregolana Shale, using 1D magnetotelluric (MT) and 1D Airborne Electromagnetic (AEM) probabilistic models, drill holes and surface geology; (2) we map the depth to basement using 1D probabilistic MT models, drill holes and interpreted structural information. Our results show that the different resolution, data sampling, depth of investigation and reliability of the utilised datasets can be combined in a complementary fashion, overcoming their respective limitations, to find solutions/models that satisfy all the datasets. We show that probabilistic workflows permit characterisation and reduce uncertainty when mapping the location of features of interest, but also permit the testing of geological hypotheses against other geophysical and geological data. These types of models are valuable to better characterise, interpret, and conceptualise the subsurface, enabling better exploration targeting and supporting efforts to discover new mineral deposits. [ABSTRACT FROM AUTHOR]

In this paper, we use a new workflow to substantiate the characterization of a prominent, deep sediment conductor in the hyperextended Bjørnøya Basin (SW Barents Sea) previously identified in smooth resistivity models from 3-D deterministic inversion of magnetotelluric data. In low-dimensionality environments like layered sedimentary basin, 1-D Bayesian inversion can be advantageous for a thorough exploration of the solution space, but the violation of the 1-D assumption has to be efficiently handled. The primary geological objectives of this work is therefore preceded by a secondary task: the application of a new machine learning approach for handling the 1-D violation assumption for 21 MT field stations in the Barents Sea. We find that a decision tree can adequately learn the relationship between MT dimensionality parameters and the 1-D–3-D residual response for a training set of synthetic models, mimicking typical resistivity structures of the SW Barents Sea. The machine learning model is then used to predict the dimensionality compensation error for MT signal periods ranging of 1–3000 s for 21 receivers located over the Bjørnøya Basin and Veslemøy High. After running 1-D Bayesian inversion, we generated a posterior resistivity distribution for an ensemble of 6000 1-D models fitting the compensated MT data for each 21 field stations. The proportion of 1-D models showing ρ < 1 Ω·m is consistently beyond 80 per cent and systemically reaches a maximum of 100 per cent in the Early Aptian–Albian interval in the Bjørnøya Basin. In hyperextended basins of the SW Barents Sea, the dimensionality compensation workflow has permitted to refine the characterization of the deep basin conductor by leveraging the increased vertical resolution and optimal used of MT data. In comparison, the smooth 3-D deterministic models only poorly constrained depth and lateral extent of the basin anomaly. The highest probability of finding ρ < 1 Ω·m is robustly assigned to the syn-tectonic Early Aptian–Albian marine shales, now buried at 6–8 km depth. Based on a theoretical two phase fluid-rock model, we show that the pore fluid of these marine shales must have a higher salinity than seawater to explain the anomaly ρ < 1 Ω·m. Therefore, the primary pore fluid underwent mixing with a secondary brine during rifting. Using analogue rift systems in palaeomargins, we argue that two possible secondary brine reservoir may contribute to deep saline fluid circulation in the hyperextended basin: (1) Permian salt-derived fluid and, (2) mantle-reacted fluid from serpentinization. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) with electroencephalography (EEG), that is TMS‐EEG, may assist in managing epilepsy. We systematically reviewed the quality of reporting and findings in TMS‐EEG studies on people with epilepsy and healthy controls, and on healthy individuals taking anti‐seizure medication. We searched the Cochrane Library, Embase, PubMed and Web of Science databases for original TMS‐EEG studies comparing people with epilepsy and healthy controls, and healthy subjects before and after taking anti‐seizure medication. Studies should involve quantitative analyses of TMS‐evoked EEG responses. We evaluated the reporting of study population characteristics and TMS‐EEG protocols (TMS sessions and equipment, TMS trials and EEG protocol), assessed the variation between protocols, and recorded the main TMS‐EEG findings. We identified 20 articles reporting 14 unique study populations and TMS methodologies. The median reporting rate for the group of people with epilepsy parameters was 3.5/7 studies and for the TMS parameters was 13/14 studies. TMS protocols varied between studies. Fifteen out of 28 anti‐seizure medication trials in total were evaluated with time‐domain analyses of single‐pulse TMS‐EEG data. Anti‐seizure medication significantly increased N45, and decreased N100 and P180 component amplitudes but in marginal numbers (N45: 8/15, N100: 7/15, P180: 6/15). Eight articles compared people with epilepsy and controls using different analyses, thus limiting comparability. The reporting quality and methodological uniformity between studies evaluating TMS‐EEG as an epilepsy biomarker is poor. The inconsistent findings question the validity of TMS‐EEG as an epilepsy biomarker. To demonstrate TMS‐EEG clinical applicability, methodology and reporting standards are required. [ABSTRACT FROM AUTHOR]

Migraine is associated with altered sensory processing, that may be evident as changes in cortical responsivity due to altered excitability, especially in migraine with aura. Cortical excitability can be directly assessed by combining transcranial magnetic stimulation with electroencephalography (TMS-EEG). We measured TMS evoked potential (TEP) amplitude and response consistency as these measures have been linked to cortical excitability but were not yet reported in migraine. We recorded 64-channel EEG during single-pulse TMS on the vertex interictally in 10 people with migraine with aura and 10 healthy controls matched for age, sex and resting motor threshold. On average 160 pulses around resting motor threshold were delivered through a circular coil in clockwise and counterclockwise direction. Trial-averaged TEP responses, frequency spectra and phase clustering (over the entire scalp as well as in frontal, central and occipital midline electrode clusters) were compared between groups, including comparison to sham-stimulation evoked responses. Migraine and control groups had a similar distribution of TEP waveforms over the scalp. In migraine with aura, TEP responses showed reduced amplitude around the frontal and occipital N100 peaks. For the migraine and control groups, responses over the scalp were affected by current direction for the primary motor cortex, somatosensory cortex and sensory association areas, but not for frontal, central or occipital midline clusters. This study provides evidence of altered TEP responses in-between attacks in migraine with aura. Decreased TEP responses around the N100 peak may be indicative of reduced cortical GABA-mediated inhibition and expand observations on enhanced cortical excitability from earlier migraine studies using more indirect measurements. [ABSTRACT FROM AUTHOR]

We propose, test and apply a methodology integrating 1D magnetotelluric (MT) and magnetic data inversion, with a focus on the characterisation of the cover–basement interface. It consists of a cooperative inversion workflow relying on standalone inversion codes. Probabilistic information about the presence of rock units is derived from MT and passed on to magnetic inversion through constraints combining structural constraints with petrophysical prior information. First, we perform the 1D probabilistic inversion of MT data for all sites and recover the respective probabilities of observing the cover–basement interface, which we interpolate to the rest of the study area. We then calculate the probabilities of observing the different rock units and partition the model into domains defined by combinations of rock units with non-zero probabilities. Third, we combine these domains with petrophysical information to apply spatially varying, disjoint interval bound constraints (DIBC) to least-squares magnetic data inversion using the alternating direction method of multipliers (or ADMM). We demonstrate the proof-of-concept using a realistic synthetic model reproducing features from the Mansfield area (Victoria, Australia) using a series of uncertainty indicators. We then apply the workflow to field data from the prospective mining region of Cloncurry (Queensland, Australia). Results indicate that our integration methodology efficiently leverages the complementarity between separate MT and magnetic data modelling approaches and can improve our capability to image the cover–basement interface. In the field application case, our findings also suggest that the proposed workflow may be useful to refine existing geological interpretations and to infer lateral variations within the basement. [ABSTRACT FROM AUTHOR]

Introduction: The lack of reliable biomarkers constrain epilepsy management. We assessed the potential of repeated transcranial magnetic stimulation with electromyography (TMS‐EMG) to track dynamical changes in cortical excitability on a within‐subject basis. Methods: We recruited people with refractory focal epilepsy who underwent video‐EEG monitoring and drug tapering as part of the presurgical evaluation. We performed daily TMS‐EMG measurements with additional postictal assessments 1–6 h following seizures to assess resting motor threshold (rMT), and motor evoked potentials (MEPs) with single‐ and paired‐pulse protocols. Anti‐seizure medication (ASM) regimens were recorded for the day before each measurement and expressed in proportion to the dosage before tapering. Additional measurements were performed in healthy controls to evaluate day‐to‐day rMT variability. Results: We performed 77 (58 baseline, 19 postictal) measurements in 16 people with focal epilepsy and 35 in seven healthy controls. Controls showed minimal day‐to‐day rMT variation. Withdrawal of ASMs was associated with a lower rMT without affecting MEPs of single‐ and paired‐pulse TMS‐EMG paradigms. Postictal measurements following focal to bilateral tonic–clonic seizures demonstrated unaltered rMT and increased short interval intracortical inhibition, while measurements following focal seizures with impaired awareness showed decreased rMT's and reduced short and long interval intracortical inhibition. Conclusion: Serial within‐subject rMT measurements yielded reproducible, stable results in healthy controls. ASM tapering and seizures had distinct effects on TMS‐EMG excitability indices in people with epilepsy. Drug tapering decreased rMT, indicating increased overall corticospinal excitability, whereas seizures affected intracortical inhibition with contrasting effects between seizure types. [ABSTRACT FROM AUTHOR]

We propose, test and apply a methodology integrating 1D magnetotelluric (MT) and magnetic data inversion, with a focus on the characterization of the cover-basement interface. It consists of a cooperative inversion workflow relying on standalone inversion codes. Probabilistic information about the presence of rock units is derived from MT and passed on to magnetic inversion through constraints combining such structural constraints with petrophysical prior information. First, we perform the 1D probabilistic inversion of MT data for all sites and recover the respective probabilities of observing the cover-basement interface, which we interpolate to the rest of the study area. We then calculate the probabilities of observing the different rock units and partition the model into domains defined by combinations of rock units with non-zero probabilities. Third, we combine such domains with petrophysical information to apply spatially-varying, disjoint interval bound constraints to least-squares magnetic data inversion. We demonstrate the proof-of-concept using a realistic synthetic model reproducing features from the Mansfield area (Victoria, Australia) using a series of uncertainty indicators. We then apply the workflow to field data from the prospective mining region of Cloncurry (Queensland, Australia). Results indicate that our integration methodology efficiently leverages the complementarity between separate MT and magnetic data modelling approaches and can improve our capability to image the cover-basement interface. In the field application case, our findings also suggest that the proposed workflow may be useful to refine existing geological interpretations and to infer lateral variations within the basement. [ABSTRACT FROM AUTHOR]

In this article we propose a workflow for creating geologically realistic depth to basement maps and apply it to the undercover area of Cloncurry, located in the Mount Isa province, Queensland. A magnetotelluric (MT) survey consisting of 457 soundings was inverted using a 1D trans‐dimensional Bayesian algorithm designed to be robust to non‐1D effects present in the data. Automated change‐point analysis was then used to derive probability distributions on basement depth for each site independently. These were laterally combined, along with drill hole data and a structural model derived from aeromagnetic and geological data, using a Bayesian estimate fusion algorithm to create a region wide depth to basement probabilistic map. Combining many different constraints in this way lead to a significant reduction in posterior uncertainty. Individual MT site change‐point posteriors were highly multi‐modal in certain areas, with multiple resistivity transitions that could correspond to the cover‐basement interface. The estimate fusion process correlates these uncertainties and the combined posterior was thus much less multi‐modal. Our results show that the sedimentary cover gradually thickens toward the north, while toward the east its thickening is controlled by a two‐steps fault system. This workflow highlights the value gained from integrating different types of geoscientific data but also shows the capability of the MT method used within a probabilistic workflow to accurately image depth to basement even using limited constraints and assumptions. Plain Language Summary: Within regions covered by sediments, defining the basement geometry underneath is essential to understand the distribution of mineral and groundwater resources. This study introduces a methodology and applies it to characterize the buried basement geometry in the Cloncurry region (90 km × 60 km area) of Queensland, which is a well‐known metallogenic province in Australia. The methodology we present uses independent estimates of depth to basement derived using data from different sources (electromagnetic geophysics and drill holes) and geological constraints on it, all providing complementary information, at many locations over the entire area. This produces a map of depth to basement, alongside a quantitative estimation of its reliability, which is based on uncertainty analysis of the various data inputs and their combination. This workflow produced a geologically realistic probability image which highlights the value of our workflow to integrate different types of data in a flexible and robust manner. Key Points: Magnetotelluric data used within a probabilistic workflow is a reliable tool to derive a realistic depth to basement probabilistic mapThe uncertainty of the probabilistic map derived can be significantly reduced by combining many different probabilistic constraintsThe semi‐automated probabilistic workflow we present is mainly data‐driven and relies on limited expert assumptions [ABSTRACT FROM AUTHOR]

Background: The most common subtypes of Guillain-Barré syndrome (GBS) are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). In the first days after the onset of weakness, standard nerve conduction studies (NCS) may not distinguish GBS subtypes. Reduced nerve excitability may be an early symptom of nerve dysfunction, which can be determined with the compound muscle action potential (CMAP) scan. The aim of this study was to explore whether early changes in motor nerve excitability in GBS patients are related to various subtypes.Methods: Prospective case-control study in 19 GBS patients from The Netherlands and 22 from Bangladesh. CMAP scans were performed within 2 days of hospital admission and NCS 7-14 days after onset of weakness. CMAP scans were also performed in age- and country-matched controls.Results: CMAP scan patterns of patients who were classified as AMAN were distinctly different compared to the CMAP scan patterns of the patients who were classified as AIDP. The most pronounced differences were found in the stimulus intensity parameters.Conclusions: CMAP scans made at hospital admission demonstrate several characteristics that can be used as an early indicator of GBS subtype. [ABSTRACT FROM AUTHOR]

Seismic full waveform inversion (FWI) is a powerful method for estimating quantitative subsurface physical parameters from seismic data. As the FWI is a nonlinear problem, the linearized approach updates model iteratively from an initial model, which can get trapped in local minima. In the presence of a high-velocity contrast, such as at Moho, the reflection coefficient and recorded waveforms from wide-aperture seismic acquisition are extremely nonlinear around critical angles. The problem at the Moho is further complicated by the interference of lower crustal (Pg) and upper mantle (Pn) turning ray arrivals with the critically reflected Moho arrivals (PmP). In order to determine velocity structure near Moho, a nonlinear method should be used. We propose to solve this strong nonlinear FWI problem at Moho using a trans-dimensional Markov chain Monte Carlo (MCMC) method, where the earth model between lower crust and upper mantle is ideally parametrized with a 1-D assumption using a variable number of velocity interfaces. Different from common MCMC methods that require determining the number of unknown as a fixed prior before inversion, trans-dimensional MCMC allows the flexibility for an automatic estimation of both the model complexity (e.g. the number of velocity interfaces) and the velocity–depth structure from the data. We first test the algorithm on synthetic data using four representative Moho models and then apply to an ocean bottom seismometer (OBS) data from the Mid-Atlantic Ocean. A 2-D finite-difference solution of an acoustic wave equation is used for data simulation at each iteration of MCMC search, for taking into account the lateral heterogeneities in the upper crust, which is constrained from traveltime tomography and is kept unchanged during inversion; the 1-D model parametrization near Moho enables an efficient search of the trans-dimensional model space. Inversion results indicate that, with very little prior and the wide-aperture seismograms, the trans-dimensional FWI method is able to infer the posterior distribution of both the number of velocity interfaces and the velocity–depth model for a strong nonlinear problem, making the inversion a complete data-driven process. The distribution of interface matches the velocity discontinuities. We find that the Moho in the study area is a transition zone of 0.7 km, or a sharp boundary with velocities from around 7 km s−1 in the lower crust to 8 km s−1 of the upper mantle; both provide nearly identical waveform match for the field data. The ambiguity comes from the resolution limit of the band-limited seismic data and limited offset range for PmP arrivals. [ABSTRACT FROM AUTHOR]

Bayesian inversion of magnetotelluric (MT) data is a powerful but computationally expensive approach to estimate the subsurface electrical conductivity distribution and associated uncertainty. Approximating the Earth subsurface with 1-D physics considerably speeds-up calculation of the forward problem, making the Bayesian approach tractable, but can lead to biased results when the assumption is violated. We propose a methodology to quantitatively compensate for the bias caused by the 1-D Earth assumption within a 1-D trans-dimensional Markov chain Monte Carlo sampler. Our approach determines site-specific likelihood functions which are calculated using a dimensionality discrepancy error model derived by a machine learning algorithm trained on a set of synthetic 3-D conductivity training images. This is achieved by exploiting known geometrical dimensional properties of the MT phase tensor. A complex synthetic model which mimics a sedimentary basin environment is used to illustrate the ability of our workflow to reliably estimate uncertainty in the inversion results, even in presence of strong 2-D and 3-D effects. Using this dimensionality discrepancy error model we demonstrate that on this synthetic data set the use of our workflow performs better in 80 per cent of the cases compared to the existing practice of using constant errors. Finally, our workflow is benchmarked against real data acquired in Queensland, Australia, and shows its ability to detect the depth to basement accurately. [ABSTRACT FROM AUTHOR]

Seismic full waveform inversion (FWI) is a state-of-the-art technique for estimating subsurface physical models from recorded seismic waveform, but its application requires care because of high non-linearity and non-uniqueness. The final outcome of global convergence from conventional FWI using local gradient information relies on an informative starting model. Bayesian inference using Markov chain Monte Carlo (MCMC) sampling is able to remove such dependence, by a direct extensive search of the model space. We use a Bayesian trans-dimensional MCMC seismic FWI method with a parsimonious dipping layer parametrization, to invert for subsurface velocity models from pre-stack seismic shot gathers that contain mainly reflections. For the synthetic study, we use a simple four-layer model and a modified Marmousi model. A recently collected multichannel off-shore seismic reflection data set, from the Lord Howe Rise (LHR) in the east of Australia, is used for the field data test. The trans-dimensional FWI method is able to provide model ensembles for describing posterior distribution, when the dipping-layer model assumption satisfies the observed data. The model assumption requires narrow models, thus only near-offset data to be used. We use model stitching with lateral and depth constraints to create larger 2-D models from many adjacent overlapping submodel inversions. The inverted 2-D velocity model from the Bayesian inference can then be used as a starting model for the gradient-based FWI, from which we are able to obtain high-resolution subsurface velocity models, as demonstrated using the synthetic data. However, lacking far-offset data limits the constraints for the low-wavenumber part of the velocity model, making the inversion highly non-unique. We found it challenging to apply the dipping-layer based Bayesian FWI to the field data. The approximations in the source wavelet and forward modelling physics increase the multimodality of the posterior distribution; the sampled velocity models clearly show the trade-off between interface depth and velocity. Numerical examples using the synthetic and field data indicate that trans-dimensional FWI has the potential for inverting earth models from reflection waveform. However, a sparse model parametrization and far offset constraints are required, especially for field application. [ABSTRACT FROM AUTHOR]

Thickness of cover over crystalline basement is an important consideration for mineral exploration in covered regions. It can be estimated from a variety of geophysical data types using a variety of inference methods. A robust method for combining such estimates to map the cover–basement interface over a region of interest is needed. Due to the large uncertainties involved, these need to be probabilistic maps. Predominantly, interpolation methods are used for this purpose, but these are built on simplifying assumptions about the inputs which are often inappropriate. The Bayesian estimate fusion is an alternative capable of addressing that issue by enabling more extensive use of domain knowledge about all inputs. This study is intended as a first step towards making the Bayesian estimate fusion a practical tool for cover thickness uncertainty mapping. The main contribution is to identify the types of data assumptions that are important for this problem, to demonstrate their importance using synthetic tests and to design a method that enables their use without introducing excessive tedium. We argue that interpolation methods like kriging often cannot achieve this goal and demonstrate that Markov chain Monte Carlo sampling can. This paper focuses on the development of statistical methodology and presents synthetic data tests designed to reflect realistic exploration scenarios on an abstract level. Intended application is for the early stages of exploration where some geophysical data are available while drill hole coverage is poor. [ABSTRACT FROM AUTHOR]

As management of respiratory distress syndrome (RDS) advances, clinicians must continually revise their current practice. We report the fourth update of "European Guidelines for the Management of RDS" by a European panel of experienced neonatologists and an expert perinatal obstetrician based on available literature up to the end of 2018. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, need for appropriate maternal transfer to a perinatal centre and timely use of antenatal steroids. Delivery room management has become more evidence-based, and protocols for lung protection including initiation of CPAP and titration of oxygen should be implemented immediately after birth. Surfactant replacement therapy is a crucial part of management of RDS, and newer protocols for its use recommend early administration and avoidance of mechanical ventilation. Methods of maintaining babies on non-invasive respiratory support have been further developed and may cause less distress and reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation using caffeine and, if necessary, postnatal steroids are also important considerations. Protocols for optimising general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome. [ABSTRACT FROM AUTHOR]

Summary: People with epilepsy need assistance and are at risk of sudden death when having convulsive seizures (CS). Automated real‐time seizure detection systems can help alert caregivers, but wearable sensors are not always tolerated. We determined algorithm settings and investigated detection performance of a video algorithm to detect CS in a residential care setting. The algorithm calculates power in the 2‐6 Hz range relative to 0.5‐12.5 Hz range in group velocity signals derived from video‐sequence optical flow. A detection threshold was found using a training set consisting of video‐electroencephalogaphy (EEG) recordings of 72 CS. A test set consisting of 24 full nights of 12 new subjects in residential care and additional recordings of 50 CS selected randomly was used to estimate performance. All data were analyzed retrospectively. The start and end of CS (generalized clonic and tonic–clonic seizures) and other seizures considered desirable to detect (long generalized tonic, hyperkinetic, and other major seizures) were annotated. The detection threshold was set to the value that obtained 97% sensitivity in the training set. Sensitivity, latency, and false detection rate (FDR) per night were calculated in the test set. A seizure was detected when the algorithm output exceeded the threshold continuously for 2 seconds. With the detection threshold determined in the training set, all CS were detected in the test set (100% sensitivity). Latency was ≤10 seconds in 78% of detections. Three/five hyperkinetic and 6/9 other major seizures were detected. Median FDR was 0.78 per night and no false detections occurred in 9/24 nights. Our algorithm could improve safety unobtrusively by automated real‐time detection of CS in video registrations, with an acceptable latency and FDR. The algorithm can also detect some other motor seizures requiring assistance. [ABSTRACT FROM AUTHOR]

Cortical excitability, as measured by transcranial magnetic stimulation combined with electromyography, is a potential biomarker for the diagnosis and follow-up of epilepsy. We report on long-interval intracortical inhibition data measured in four different centres in healthy controls (n = 95), subjects with refractory genetic generalized epilepsy (n = 40) and with refractory focal epilepsy (n = 69). Long-interval intracortical inhibition was measured by applying two supra-threshold stimuli with an interstimulus interval of 50, 100, 150, 200 and 250 ms and calculating the ratio between the response to the second (test stimulus) and to the first (conditioning stimulus). In all subjects, the median response ratio showed inhibition at all interstimulus intervals. Using a mixed linear-effects model, we compared the long-interval intracortical inhibition response ratios between the different subject types. We conducted two analyses; one including data from the four centres and one excluding data from Centre 2, as the methods in this centre differed from the others. In the first analysis, we found no differences in long-interval intracortical inhibition between the different subject types. In all subjects, the response ratios at interstimulus intervals 100 and 150 ms showed significantly more inhibition than the response ratios at 50, 200 and 250 ms. Our second analysis showed a significant interaction between interstimulus interval and subject type (P = 0.0003). Post hoc testing showed significant differences between controls and refractory focal epilepsy at interstimulus intervals of 100 ms (P = 0.02) and 200 ms (P = 0.04). There were no significant differences between controls and refractory generalized epilepsy groups or between the refractory generalized and focal epilepsy groups. Our results do not support the body of previous work that suggests that long-interval intracortical inhibition is significantly reduced in refractory focal and genetic generalized epilepsy. Results from the second analysis are even in sharper contrast with previous work, showing inhibition in refractory focal epilepsy at 200 ms instead of facilitation previously reported. Methodological differences, especially shorter intervals between the pulse pairs, may have contributed to our inability to reproduce previous findings. Based on our results, we suggest that long-interval intracortical inhibition as measured by transcranial magnetic stimulation and electromyography is unlikely to have clinical use as a biomarker of epilepsy. [ABSTRACT FROM AUTHOR]

It is not fully understood how seizures terminate and why some seizures are followed by a period of complete brain activity suppression, postictal generalized EEG suppression. This is clinically relevant as there is a potential association between postictal generalized EEG suppression, cardiorespiratory arrest and sudden death following a seizure. We combined human encephalographic seizure data with data of a computational model of seizures to elucidate the neuronal network dynamics underlying seizure termination and the postictal generalized EEG suppression state. A multi-unit computational neural mass model of epileptic seizure termination and postictal recovery was developed. The model provided three predictions that were validated in EEG recordings of 48 convulsive seizures from 48 subjects with refractory focal epilepsy (20 females, age range 15-61 years). The duration of ictal and postictal generalized EEG suppression periods in human EEG followed a gamma probability distribution indicative of a deterministic process (shape parameter 2.6 and 1.5, respectively) as predicted by the model. In the model and in humans, the time between two clonic bursts increased exponentially from the start of the clonic phase of the seizure. The terminal interclonic interval, calculated using the projected terminal value of the log-linear fit of the clonic frequency decrease was correlated with the presence and duration of postictal suppression. The projected terminal interclonic interval explained 41% of the variation in postictal generalized EEG suppression duration (P < 0.02). Conversely, postictal generalized EEG suppression duration explained 34% of the variation in the last interclonic interval duration. Our findings suggest that postictal generalized EEG suppression is a separate brain state and that seizure termination is a plastic and autonomous process, reflected in increased duration of interclonic intervals that determine the duration of postictal generalized EEG suppression. [ABSTRACT FROM AUTHOR]

Background: Pregnancies complicated by maternal diabetes are associated with disproportionate intrauterine growth that subsequently may lead to pediatric adiposity. Objectives: We investigated whether disproportionate intrauterine growth leads to differences in BMI in 4- to 5-year-old offspring from pregnancies complicated by type 1 (ODM1), type 2 (ODM2), or gestational diabetes (OGDM). Methods: Ultrasound data of fetal head-to-abdominal circumference (HC/AC) ratio obtained between 32 and 36 weeks of gestational age were related to offspring anthropometrics that were retrieved from infant welfare centers. Results: Data from 27 ODM1, 22 ODM2, and 24 OGDM were obtained. Ultrasound measurements for the HC/AC ratio were performed at a mean of 33-34 weeks, with a mean Z-score of the HC/AC ratio of -0.801, -0.879, and 0.017 in ODM1, ODM2, and OGDM. Mean BMI SDS was highest in ODM2 as compared to ODM1 and OGDM. In ODM1 there was a negative correlation between HC/AC ratio and BMI SDS at the ages of 4 and 5 years, but not in ODM2 or OGDM. The birth weight Z-score was positively correlated to BMI SDS in ODM2 and OGDM. Conclusion: Disproportionate intrauterine growth, expressed as the HC/AC ratio, was inversely related with BMI SDS in ODM1 at the ages of 4-5 years, but not in ODM2 or OGDM. Weight and maybe obesity in ODM1 offspring are likely to be related to intrauterine adiposity, whereas overweight in ODM2 and OGDM offspring seems more related to other factors such as birth weight centile, maternal obesity, and altered lifestyle factors during childhood. [ABSTRACT FROM AUTHOR]

Objective Following a sudden death at a residential care unit, the Dutch Health and Care Inspectorate advised intensification of the use of video monitoring ( VM) at the unit. We assessed whether VM resulted in increased identification of seizures that required clinical intervention. Methods The unit provides care for 340 individuals with refractory epilepsy and severe learning disabilities. Acoustic detection systems ( ADSs) cover all individuals; 37 people also have a bed motion sensor ( BMS) and 46 people with possible nocturnal seizures are now monitored by VM. During a 6-month period, in all cases of a suspected seizure we asked the caregivers to specify which device alerted them and to indicate whether this led to an intervention. Staff costs of VM were estimated using payroll information. Results We identified 1,208 seizures in 37 individuals: 4 had no nocturnal seizures and 393 (33%) seizures were seen only on video. In 169 (14%) of 1,208 seizures an intervention was made and this included 39 (10%) of 393 seizures seen only on video. When compared to seizures observed with an ADS or BMS, seizures seen only on video were more often tonic seizures (71% vs. 22%, p < 0.001) and occurred mostly in the beginning or at the end of the night (40% vs. 26%, p < 0.001). The extra staff costs of monitoring was 7,035 euro per seizure seen only on video and leading to an intervention. Significance VM facilitates nocturnal surveillance, but the costs are high. This underscores the need for development of reliable seizure detection devices. [ABSTRACT FROM AUTHOR]

People with epilepsy often report seizures precipitated by stress. This is believed to be due to effects of stress hormones, such as cortisol, on neuronal excitability. Cortisol, regardless of stress, is released in hourly pulses, whose effect on epileptic activity is unknown. We tested the relation between cortisol levels and the incidence of epileptiform abnormalities in the electroencephalogram of people with focal epilepsy. Morning cortisol levels were measured in saliva samples obtained every 15 min. Interictal epileptiform discharges were determined in the same time periods. We investigated the relationship between cortisol levels and the epileptiform discharges distinguishing persons with from those without stress-precipitated seizures (linear mixed model), and analysed the contribution of individual, epilepsy and recording characteristics with multivariable analysis. Twenty-nine recordings were performed in 21 individuals. Cortisol was positively related to incidence of epileptiform discharges (β = 0.26, P = 0.002) in people reporting stress-sensitive seizures, but not those who did not report stress sensitivity (β = -0.07, P = 0.64). The relationship between cortisol and epileptiform discharges was positively associated only with stress sensitivity of seizures (β = 0.31, P = 0.005). The relationship between cortisol levels and incidence of interictal epileptiform discharges in people with stress-sensitive seizures suggests that stress hormones influence disease activity in epilepsy, also under basal conditions. [ABSTRACT FROM AUTHOR]

Objectives: To compare electroencephalography (EEG) findings during pregnancy and postpartum in women with normotensive pregnancies and pregnancies complicated by hypertensive disorders. Also the health related quality of life postpartum was related to these EEG findings. Materials and Methods: An observational case-control study in a university hospital in the Netherlands. Twenty-nine normotensive and 58 hypertensive pregnant women were included. EEG’s were recorded on several occasions during pregnancy and 6–8 weeks postpartum. Postpartum, the women filled out health related quality of life questionnaires. Main outcome measures were qualitative and quantitative assessments on EEG, multidimensional fatigue inventory, Short Form (36) Health Survey and EuroQoL visual analogue scale. Results: In women with severe preeclampsia significantly lower alpha peak frequency, more delta and theta activity bilaterally and a higher EEG Sum Score were seen. Postpartum, these women showed impaired mental health, mental fatigue and social functioning, which could not be related to the EEG findings. Conclusions: Severe preeclamptic patients show more EEG abnormalities and have impaired mental wellbeing postpartum, but these findings are not correlated. [ABSTRACT FROM AUTHOR]

Introduction: Fasciculations, the spontaneous activity of single motor units (MUs) are characteristic, but nonspecific for motor neuron disease (MND). We aimed to identify MU discharge properties to optimally differentiate MND patients from healthy controls.Methods: High-density surface electromyography recordings were performed in the thenar muscles during 10 min of rest. MU discharges were classified as "isolated" when the interspike intervals (ISIs) before and after were > 250 ms, "continual" when both ISIs were ≤ 250 ms, or as "other".Results: In patients (n = 30) compared with controls (n = 14), more MUs were active (9 vs. 3, P < 0.001) and generated relatively more isolated discharges (35% vs. 10%, P = 0.01). Two or more MUs with isolated discharges occurred more frequently in patients compared with controls (24% vs. <1% of 10-s windows, P < 0.001).Conclusions: More frequent occurrence of multiple MUs showing isolated discharges may improve identification of patients with MND. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to determine whether electrically evoked multiplet discharges (MDs) are related to severity of clinical deterioration in motor neuron disease (MND).Methods: Stimulated high-density surface electromyographic (HDsEMG) recordings were performed in thenar muscles. Data were collected from 31 MND patients. MDs from the HDsEMG recordings were determined at baseline. ALSFRS-R scores were obtained at baseline and at a maximum of 16 weeks follow-up.Results: The presence of MDs was associated with progressive deterioration of ALSFRS-R score (P = 0.02) and fine motor function (FMF) (P < 0.001). Patients who had a higher number of motor units that generated MDs (r = 0.61, P < 0.001) and patients who had a higher number of MDs (as percentage of applied stimuli) (r = 0.59, P = 0.001) had a more severe decline in FMF.Conclusions: Electrically evoked MDs are associated with more marked clinical deterioration in patients with MND. [ABSTRACT FROM AUTHOR]

Objective: To determine and compare the diagnostic accuracy of electrically elicited multiplet discharges (MDs) and fasciculation potentials (FPs) in motor neuron disease (MND).Methods: Patients were eligible when they had MND in their differential diagnosis and were referred for electromyogram (EMG). Stimulated high-density surface EMG of the thenar muscles was performed on the same day as standard EMG examination. High-density recordings were analysed for presence of MDs and needle EMG of any muscle investigated in the cervical region for presence of FPs.Results: Of the 61 patients enrolled in this diagnostic study, 24 patients were clinically diagnosed with amyotrophic lateral sclerosis (ALS) and 11 patients with progressive muscular atrophy (PMA). Another diagnosis was made in 26 patients. Sixteen patients in whom MDs were detected were diagnosed with either ALS (n = 11) or PMA (n = 5; sensitivity = 47.1%, PPV = 94.1%). MDs were detected in only one patient initially diagnosed with PMA, but in whom later on, multifocal motor neuropathy could not be excluded (specificity = 96.2%). Electrically elicited MDs had a higher specificity than FPs (96.2% vs 53.9%, p < 0.001, n = 26) and lower sensitivity (47.1% vs 85.3%, p = 0.002, n = 34). When considering presence of MDs in MND as neurogenic EMG abnormality, lower motor neuron involvement of ≥ 1 EMG region increased from 50% to 73.5% (p = 0.008, n = 34).Conclusions: Electrically evoked MDs are highly specific for ALS and PMA and are an early sign of lower motor neuron dysfunction. [ABSTRACT FROM AUTHOR]

High frequency oscillations (HFO) appear to be a promising marker for delineating the seizure onset zone (SOZ) in patients with localization related epilepsy. It remains, however, a purely observational phenomenon and no common mechanism has been proposed to relate HFOs and seizure generation. In this work we show that a cascade of two computational models, one on detailed compartmental scale and a second one on neural mass scale can explain both the autonomous generation of HFOs and the presence of epileptic seizures as emergent properties. To this end we introduce axonal-axonal gap junctions on a microscopic level and explore their impact on the higher level neural mass model (NMM). We show that the addition of gap junctions can generate HFOs and simultaneously shift the operational point of the NMM from a steady state network into bistable behavior that can autonomously generate epileptic seizures. The epileptic properties of the system, or the probability to generate epileptic type of activity, increases gradually with the increase of the density of axonal-axonal gap junctions. We further demonstrate that ad hoc HFO detectors used in previous studies are applicable to our simulated data. [ABSTRACT FROM AUTHOR]

In addition to cerebrovascular resistance (CVR) zero flow pressure (ZFP), effective cerebral perfusion pressure (CPPe) and the resistance area product (RAP) are supplemental determinants of cerebral blood flow (CBF). Until now, the interrelationship of PaCO2-induced changes in CBF, CVR, CPPe, ZFP, and RAP is not fully understood. In a controlled crossover trial, we investigated 10 anesthetized patients aiming at PaCO2 levels of 30, 37, 43, and 50 mm Hg. Cerebral blood flow was measured with a modified Kety-Schmidt-technique. Zero flow pressure and RAP was estimated by linear regression analysis of pressure-flow velocity relationships of the middle cerebral artery. Effective cerebral perfusion pressure was calculated as the difference between mean arterial pressure and ZFP, CVR as the ratio CPPe/CBF. Statistical analysis was performed by one-way RM-ANOVA. When comparing hypocapnia with hypercapnia, CBF showed a significant exponential reduction by 55% and mean VMCA by 41%. Effective cerebral perfusion pressure linearly decreased by 17% while ZFP increased from 14 to 29 mm Hg. Cerebrovascular resistance increased by 96% and RAP by 39%; despite these concordant changes in mean CVR and Doppler-derived RAP correlation between these variables was weak (r=0.43). In conclusion, under general anesthesia hypocapnia-induced reduction in CBF is caused by both an increase in CVR and a decrease in CPPe, as a consequence of an increase in ZFP. [ABSTRACT FROM AUTHOR]

A novel automated algorithm is proposed to approximate the seizure onset zone (SOZ), while providing reproducible output. The SOZ, a surrogate marker for the epileptogenic zone (EZ), was approximated from intracranial electroencephalograms (iEEG) of nine people with temporal lobe epilepsy (TLE), using three methods: (1) Total ripple length (TRL): Manually segmented high-frequency oscillations, (2) Rippleness (R): Area under the curve (AUC) of the autocorrelation functions envelope, and (3) Autoregressive model residual variation (ARR, novel algorithm): Time-variation of residuals from autoregressive models of iEEG windows. TRL, R, and ARR results were compared in terms of separability, using Kolmogorov-Smirnov tests, and performance, using receiver operating characteristic (ROC) curves, to the gold standard for SOZ delineation: visual observation of ictal video-iEEGs. TRL, R, and ARR can distinguish signals from iEEG channels located within the SOZ from those outside it (p < 0.01). The ROC AUC was 0.82 for ARR, while it was 0.79 for TRL, and 0.64 for R. ARR outperforms TRL and R, and may be applied to identify channels in the SOZ automatically in interictal iEEGs of people with TLE. ARR, interpreted as evidence for nonharmonicity of high-frequency EEG components, could provide a new way to delineate the EZ, thus contributing to presurgical workup. [ABSTRACT FROM AUTHOR]

Objective To define reference values of the patellar reflex in normotensive pregnant and postpartum women and to compare these with values in women with preeclampsia. Design Observational study. Setting University teaching hospital in the Netherlands. Population Normotensive non-pregnant women, pregnant women and preeclamptic women. Methods In normotensive pregnant women the patellar reflex was cross-sectionally recorded using surface electromyography at four time points during pregnancy and six to eight weeks postpartum. In non-pregnant normotensive women this was recorded once. Preeclamptic women were recorded during pregnancy and postpartum. Main outcome measures Latency and amplitude of the compound muscle action potential of the patellar reflex. Results Latency and amplitude of the compound muscle action potential during normotensive pregnancies showed no changes compared with the non-pregnant state during reproductive age. Latency of the compound muscle action potential was increased in pregnancies with severe preeclampsia compared with normotensive pregnancies. These differences disappeared postpartum. Conclusions During pregnancy, the patellar reflex can be assessed using surface electromyography. Latency and amplitude show no changes during normotensive pregnancies and are no different from the postpartum or non-pregnant values. In severely preeclamptic women, latency is increased. The clinical value of this is limited. [ABSTRACT FROM AUTHOR]

Cerebral perfusion pressure ( CPP) is elevated in preeclampsia, and may predispose to cerebrovascular complications and progression to eclampsia. We estimated zero flow pressure ( ZFP) and CPP using simultaneously obtained arterial blood pressure and middle cerebral artery blood flow velocity in 10 women with preeclampsia, all treated with methyldopa with or without nifedipine, and 18 healthy pregnant controls. Mean ± SD ZFP was lower in women with preeclampsia than in controls (16.8 ± 10.9 vs. 31.7 ± 15.0 mmHg, p = 0.01) whereas CPP was considerably higher (82.3 ± 17.7 vs. 55.0 ± 11.7 mmHg, p < 0.001), as was the cerebral flow index (41.9 ± 18.0 vs. 25.6 ± 11.2, p = 0.02). There was a significant correlation between blood pressure and CPP in women with preeclampsia, but not in controls. Women with preeclampsia may have an increased cerebral perfusion due to a reduced ZFP and increased CPP despite treatment with antihypertensive medication. More rigorous antihypertensive therapy, aimed at reducing CPP, could result in a decrease in cerebral complications in women with preeclampsia. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) can be used for safe, noninvasive probing of cortical excitability (CE). We review 50 studies that measured CE in people with epilepsy. Most showed cortical hyperexcitability, which can be corrected with anti-epileptic drug treatment. Several studies showed that decrease of CE after epilepsy surgery is predictive of good seizure outcome. CE is a potential biomarker for epilepsy. Clinical application may include outcome prediction of drug treatment and epilepsy surgery. [ABSTRACT FROM AUTHOR]

Even though it is known that neonatal seizures are associated with acute brain lesions, the relationship of electroencephalographic (EEG) seizures to acute perinatal brain lesions visible on magnetic resonance imaging (MRI) has not been objectively studied. EEG source localization is successfully used for this purpose in adults, but it has not been sufficiently explored in neonates. Therefore, we developed an integrated method for ictal EEG dipole source localization based on a realistic head model to investigate the utility of EEG source imaging in neonates with postasphyxial seizures. We describe here our method and compare the dipole seizure localization results with acute perinatal lesions seen on brain MRI in 10 full-term infants with neonatal encephalopathy. Through experimental studies, we also explore the sensitivity of our method to the electrode positioning errors and the variations in neonatal skull geometry and conductivity. The localization results of 45 focal seizures from 10 neonates are compared with the visual analysis of EEG and MRI data, scored by expert physicians. In 9 of 10 neonates, dipole locations showed good relationship with MRI lesions and clinical data. Our experimental results also suggest that the variations in the used values for skull conductivity or thickness have little effect on the dipole localization, whereas inaccurate electrode positioning can reduce the accuracy of source estimates. The performance of our fused method indicates that ictal EEG source imaging is feasible in neonates and with further validation studies, this technique can become a useful diagnostic tool. Hum Brain Mapp 34:2402-2417, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The electroencephalography ( EEG) signal has a high complexity, and the process of extracting clinically relevant features is achieved by visual analysis of the recordings. The interobserver agreement in EEG interpretation is only moderate. This is partly due to the method of reporting the findings in free-text format. The purpose of our endeavor was to create a computer-based system for EEG assessment and reporting, where the physicians would construct the reports by choosing from predefined elements for each relevant EEG feature, as well as the clinical phenomena (for video- EEG recordings). A working group of EEG experts took part in consensus workshops in Dianalund, Denmark, in 2010 and 2011. The faculty was approved by the Commission on European Affairs of the International League Against Epilepsy (ILAE). The working group produced a consensus proposal that went through a pan- European review process, organized by the European Chapter of the International Federation of Clinical Neurophysiology. The Standardised Computer-based Organised Reporting of EEG ( SCORE) software was constructed based on the terms and features of the consensus statement and it was tested in the clinical practice. The main elements of SCORE are the following: personal data of the patient, referral data, recording conditions, modulators, background activity, drowsiness and sleep, interictal findings, 'episodes' (clinical or subclinical events), physiologic patterns, patterns of uncertain significance, artifacts, polygraphic channels, and diagnostic significance. The following specific aspects of the neonatal EEGs are scored: alertness, temporal organization, and spatial organization. For each EEG finding, relevant features are scored using predefined terms. Definitions are provided for all EEG terms and features. SCORE can potentially improve the quality of EEG assessment and reporting; it will help incorporate the results of computer-assisted analysis into the report, it will make possible the build-up of a multinational database, and it will help in training young neurophysiologists. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) and progressive muscular atrophy (PMA) are characterized by a loss of motor units (MUs), reinnervation and, eventually, muscle fibre loss. These three aspects are all reflected in the compound muscle action potential scan (CMAP scan, a high-detail stimulus response curve), which visualizes large MU potentials as 'steps'. We explored changes in the CMAP scan over time, combined the information on steps and CMAP amplitude into a CMAP scan-based progression score (CSPS), and correlated this score with motor unit number estimates (MUNE). Ten patients (three PMA, seven ALS; age 37−77 years) were included. CMAP scan and MUNE measurements were performed five times during a three-month period. Nine patients had additional measurements. The follow-up period was 3−24 months. Results demonstrated that abnormalities in steps preceded a decline in maximum CMAP amplitude during follow-up. Usually, both steps and maximum CMAP amplitude changed between recordings. The correlation between the CSPS and MUNE was −0.80 ( p < 0.01). In conclusion, the CMAP scan can be used to visualize and quantify disease progression in a muscle affected by MND. The CSPS is a measure of MU loss that is quick and easy to obtain and that, in contrast to MUNE, has no sample bias. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) and progressive muscular atrophy (PMA) are characterized by a loss of motor units (MUs), reinnervation and, eventually, muscle fibre loss. These three aspects are all reflected in the compound muscle action potential scan (CMAP scan, a high-detail stimulus response curve), which visualizes large MU potentials as 'steps'. We explored changes in the CMAP scan over time, combined the information on steps and CMAP amplitude into a CMAP scan-based progression score (CSPS), and correlated this score with motor unit number estimates (MUNE). Ten patients (three PMA, seven ALS; age 37−77 years) were included. CMAP scan and MUNE measurements were performed five times during a three-month period. Nine patients had additional measurements. The follow-up period was 3−24 months. Results demonstrated that abnormalities in steps preceded a decline in maximum CMAP amplitude during follow-up. Usually, both steps and maximum CMAP amplitude changed between recordings. The correlation between the CSPS and MUNE was −0.80 (p < 0.01). In conclusion, the CMAP scan can be used to visualize and quantify disease progression in a muscle affected by MND. The CSPS is a measure of MU loss that is quick and easy to obtain and that, in contrast to MUNE, has no sample bias. [ABSTRACT FROM AUTHOR]

Typical Miller Fisher syndrome (MFS) lacks limb muscle weakness, but some patients may unpredictably progress to severe Guillain-Barré syndrome. The compound muscle action potential (CMAP) scan is a recently developed non-invasive, painless, and reproducible method for detecting early changes in motor nerve excitability. This technique was used to monitor subclinical limb motor nerve dysfunction during disease course in typical MFS. Three Miller Fisher patients with preserved limb muscle strength and normal routine nerve conduction studies were included. Frequent serial CMAP scanning of the median nerve was performed during acute phase and follow-up and was related to clinical course and outcome. All patients showed an abnormal increase in the range of stimulus intensities at the day of hospital admission, indicating reduced motor nerve excitability already at the earliest stage of disease. Median nerve dysfunction progressed in parallel or even before clinical deterioration, and improved with clinical recovery. Our study shows that typical MFS is a more general neuropathy, affecting peripheral motor nerves even in patients with preserved limb strength and conduction velocity. CMAP scanning is a sensitive technique for early detection of subclinical motor nerve dysfunction and for monitoring disease activity in immune-mediated neuropathies. [ABSTRACT FROM AUTHOR]

We hypothesized that action potentials evoked by distal stimulation might trigger ectopic activity (multiplet discharges, MDs). By studying MDs, we investigated the involvement of the axonal part of the peripheral motor neuron in amyotrophic lateral sclerosis (ALS) and progressive muscular atrophy (PMA). We performed stimulated high-density surface EMG recordings of the thenar muscles in 10 ALS/PMA patients, five recordings per patient over a three-month period. Furthermore, motor unit number estimates (MUNE) and ALSFRS-R scores were obtained in sessions 1 and 5. MDs were found in all patients, in 21% of the sampled motor units, and in response to 2.4% of the stimulations. The interspike interval range of the MD components was 2.9-6.5 ms, which is compatible only with a distal MD origin. The number of MDs, as percentage of the number of applied stimuli, was correlated with a decline in ALSFRS-R ( r =0.80, p =0.006) and MUNE ( r =0.72, p =0.02). In conclusion, MDs can be elicited with electrical stimulation in ALS and PMA patients. Analysis of MD characteristics provides further indications for pathophysiological excitability changes in the most distal part of the motor neuron. MDs are associated with clinical deterioration. [ABSTRACT FROM AUTHOR]

Background: Danon disease is a neuromuscular disorder with variable expression in the eye. We describe a family with Danon disease and cone-rod dystrophy (CRD). Methods: Affected males of one family with Danon were invited for an extensive ophthalmologic examination, including color vision testing, fundus photography, Goldmann perimetry, full-field electroretinogram (ERG), and SD-OCT. Previous ophthalmologic data were retrieved from medical charts. The LAMP2 and RPGR gene were analyzed by direct sequencing. Results: Two siblings had no ocular phenotype. The third sibling and a cousin developed CRD leading to legal blindness. Visual acuity deteriorated progressively over time, color vision was severely disturbed, and ERG showed reduced photopic and scotopic responses. SD-OCT revealed thinning of the photoreceptor and RPE layer. Visual fields demonstrated central scotoma. The causal mutation was p.Gly384Arg in LAMP2; no mutations were found in RPGR. Conclusions: This is the first description of CRD in Danon disease. The retinal phenotype was a late onset but severe dystrophy characterized by loss of photoreceptors and RPE cells. With this report, we highlight the importance of a comprehensive ophthalmologic examination in the clinical work-up of Danon disease. [ABSTRACT FROM AUTHOR]

Background: In Guillain-Barré syndrome (GBS), the diversity in electrophysiological subtypes is unexplained but may be determined by geographical factors and preceding infections. Acute motor axonal neuropathy (AMAN) is a frequent GBS variant in Japan and one study proposed that in Japan, Campylobacter jejuni infections exclusively elicit AMAN. In The Netherlands C jejuni is the predominant type of preceding infection yet AMAN is rare. This may indicate that not all Dutch GBS patients with C jejuni infections have AMAN.Objective: To determine if GBS patients with a preceding C jejuni infection in The Netherlands exclusively have AMAN.Methods: Retrospective analysis of preceding infections in relation to serial electrophysiology and clinical data from 123 GBS patients. C jejuni related cases were defined as having preceding diarrhoea and positive C jejuni serology. Electrophysiological characteristics in C jejuni related cases were compared with those in viral related GBS patients. In addition, eight GBS patients from another cohort with positive stool cultures for C jejuni were analysed.Results: 17 (14%) of 123 patients had C jejuni related GBS. C jejuni patients had lower motor and higher sensory action potentials compared with viral related cases. Nine (53%) C jejuni patients had either AMAN or inexcitable nerves. However, three (18%) patients fulfilled the criteria for acute inflammatory demyelinating polyneuropathy (AIDP). Also, two (25%) of eight additional patients with a C jejuni positive stool sample had AIDP.Conclusion: In The Netherlands, C jejuni infections are strongly, but not exclusively, associated with axonal GBS. Some patients with these infections fulfil current criteria for demyelination. [ABSTRACT FROM AUTHOR]

Ultrasound-guided near-nerve neurography is a new tool that can be used to assess nerve regeneration before reinnervation occurs. In this study, ultrasound-guided near-nerve measurements were validated against axon diameter counts in rabbits during a 15-week regeneration period after a crush lesion of their peroneal nerve. The course of the nerve was determined ultrasonically, and the active near-nerve needle electrode was maneuvered just next to the nerve under ultrasound guidance. Measured action potentials were compared with axon diameter counts from histological sections of these same nerves. A moderate to good positive correlation was found, which reached a maximum of 0.7 at a cut-off of 3 μm, corresponding to the minimal size of the myelinated axons. Our results suggest that, following a similar validation study in humans, ultrasound-guided near-nerve neurography may be clinically useful when early evaluation of nerve activity is needed. Muscle Nerve, 2009 [ABSTRACT FROM AUTHOR]

We describe the neurological, electrophysiological, and genetic features of autosomal dominant distal hereditary motor neuronopathy (HMN) in a three generation Dutch family, including 12 patients with distal muscle weakness and atrophy. The severity of disease ranged from disabling muscle weakness to a subclinical phenotype. Neurologic exams of nine patients and nerve conduction studies (NCS) and myography in five endorsed the variable presentations of HMN in this family, including patients with only lower (four), upper (one), or both upper and lower extremities involvement (four). Asymmetrical or strictly unilateral disease was noted in three patients. Three also showed pyramidal features. A genome-wide search combining SNP arrays (250K) with parametric linkage analysis identified a novel locus on chromosome 16p (mLOD=3.28) spanning 6 Mb (rs6500882–rs7192086). Direct sequencing excluded mutations in the SIMPLE/LITAF gene (mapping to the 16p locus) and identified a pathogenic mutation (p.N88S) in BCLS2 (11q12–q14). All 12 affected relatives had the BSCL2 mutation and the chromosome 16p haplotype and showed features of motor neuron degeneration. One patient had a very mild phenotype with bilateral pes cavus, normal concentric needle electromyography but signs of motor neuron involvement at electrophysiological muscle scan (EMS). Similar EMS abnormalities in addition to abnormal NCS and myography were observed in a clinically unaffected person (carrying only the 16p haplotype). These results expand the clinical spectrum of HMN and suggest a digenic inheritance of HMN in this family with a BSCL2 mutation and a chromosome 16 locus likely contributing to the phenotype. [ABSTRACT FROM AUTHOR]