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Purpose To evaluate whether the onset of pediatric refractory status epilepticus (rSE) is related to time of day. Method We analyzed the time of day for the onset of rSE in this prospective observational study performed from June 2011 to May 2019 in pediatric patients (1 month to 21 years of age). We evaluated the temporal distribution of pediatric rSE utilizing a cosinor analysis. We calculated the midline estimating statistic of rhythm (MESOR) and amplitude. MESOR is the estimated mean number of rSE episodes per hour if they were evenly distributed. Amplitude is the difference between MESOR and maximum rSE episodes/hour, or between MESOR and minimum rSE episodes/hour. We also evaluated the temporal distribution of time to treatment. Results We analyzed 368 patients (58% males) with a median (p25 – p75) age of 4.2 (1.3–9.7) years. The MESOR was 15.3 (95% CI: 13.9–16.8) and the amplitude was 3.2 (95% CI: 1.1–5.3), p = 0.0024, demonstrating that the distribution is not uniform, but better described as varying throughout the day with a peak in the morning (11am–12 pm) and trough at night (11 pm–12 am). The duration from rSE onset to application of the first non-benzodiazepine antiseizure medication peaked during the early morning (2am–3 am) with a minimum during the afternoon (2 pm–3 pm) (p = 0.0179). Conclusions The distribution of rSE onset is not uniform during the day. rSE onset shows a 24-h distribution with a peak in the mid-morning (11am–12 pm) and a trough at night (11 pm-12am).

Improved non-invasive localization of the epileptogenic foci prior to epilepsy surgery would improve surgical outcome in patients with partial seizure disorders. A critical component for the identification of the epileptogenic brain is the analysis of electrophysiological data obtained during ictal activity from prolonged intracranial recordings. The development of a noninvasive means to identify the seizure onset zone (SOZ) would thus play an important role in treating patients with intractable epilepsy. In the present study, we have investigated non-invasive imaging of epileptiform activity in patients with medically intractable epilepsy by means of a cortical potential imaging (CPI) technique. Eight pediatric patients (1M/7F, ages 4-14 years) with intractable partial epilepsy were studied. Each patient had multiple (6 to 14) interictal spikes (IIS) subjected to the CPI analysis. Realistic geometry boundary element head models were built using each individual's MRI in order to maximize the imaging precision. CPI analysis was performed on the IISs, and extrema in the estimated CPI images were compared with SOZs as determined from the ictal electrocorticogram (ECoG) recordings, as well as the resected areas in the patients and surgical outcomes. The distances between the maximum cortical activities of the IISs reflected by the estimated cortical potential distributions and the SOZs were determined to quantitatively evaluate the performance of the CPI in localizing the epileptogenic zone. Ictal ECoG recordings revealed that six patients exhibited a single epileptogenic focus while two patients had multiple foci. In each patient, the CPI results revealed an area of activity overlapping with the SOZs as identified by ictal ECoG. The distance from the extreme of the CPI images at the peak of IIS to the nearest intracranial electrode associated with the onset of the ictal activity was evaluated for each patient and the averaged distance was 4.6mm. In the group of patients studied, the CPI imaged epileptogenic foci were within the resected areas. According to the follow-up of the eight patients included, two were seizure free and six had substantial reduction in seizure frequency. These promising results demonstrate the potential for noninvasive localization of the epileptogenic focus from interictal scalp EEG recordings. Confirmation of our results may have a significant impact on the process of presurgical planning in pediatric patients with intractable epilepsy by dramatically reducing or potentially eliminating the use of intracranial recording.

The antiepileptic drug felbamate has demonstrated efficacy against a variety of seizure types in the pediatric population, particularly seizures associated with Lennox-Gastaut syndrome. Postmarketing experience, however, revealed serious idiosyncratic adverse effects not observed during clinical trials, including aplastic anemia and liver failure. As a result, many physicians have been hesitant to prescribe felbamate. This retrospective study evaluated the efficacy of felbamate in a pediatric population with intractable epilepsy. Of 38 patients, 22 had Lennox-Gastaut syndrome (58%); 6 had myoclonic-astatic epilepsy of Doose (16%); 5 had symptomatic generalized epilepsy, not otherwise specified (13%); and 5 had symptomatic localization-related epilepsy (13%). Most patients had multiple seizure types and had been tried on a variety of antiepileptic medications. With felbamate treatment, 6 patients (16%) became seizure free, including 4 of the 6 patients with myoclonic-astatic epilepsy of Doose; 24 patients (63%) had a greater than 50% reduction in seizure frequency. In this population felbamate appeared to be safe, with minimal adverse effects. The study is limited by the small number of patients and by its retrospective nature, but nonetheless adds to the evidence that felbamate is an important antiepileptic drug for medically refractory epilepsy in children and is well tolerated with few adverse effects.

This paper reports the findings from a pilot study of four patients with medically refractory epilepsy undergoing pre-surgical evaluation with ages ranging from 5 to 17 years. Video electroencephalography recordings and data from a near infrared spectroscopy cerebral/somatic oximeter were gathered and related to electrographic seizure onset and offset as determined by a paediatric epileptologist. All four patients showed haemodynamic changes associated with epileptiform activities. The increased blood flow clearly coincided with epileptiform activity and continued to increase as the epileptiform activity built up. Regional cerebral oxygen saturation increased in the epileptogenic focus, perhaps due to loss of cerebrovascular autoregulation. These findings reinforce that near infrared spectroscopy can potentially be used in a wide spectrum of patients with epilepsy regardless of the underlying brain pathology.

In the present study, we have validated the cortical potential imaging (CPI) technique for estimating cortical potentials from scalp EEG using simultaneously recorded electrocorticogram (ECoG) in the presence of strong local inhomogeneity, i.e. Silastic ECoG grid(s). The finite element method (FEM) was used to model the realistic post-operative head volume conductor, which includes the scalp, skull, cerebrospinal fluid (CSF) and brain, as well as the Silastic ECoG grid(s) implanted during the surgical evaluation in epilepsy patients, from the co-registered magnetic resonance (MR) and computer tomography (CT) images. A series of computer simulations were conducted to evaluate the present FEM-based CPI technique, and to assess the effect of the Silastic ECoG grid on the scalp EEG forward solutions. The present simulation results show that the Silastic ECoG grid has substantial influence on the scalp potential forward solution due to the distortion of current pathways in the presence of the extremely low conductivity materials. On the other hand, its influence on the estimated cortical potential distribution is much less than that on the scalp potential distribution. With appropriate numerical modeling and inverse estimation techniques, we have demonstrated the feasibility of estimating the cortical potentials from the scalp EEG with the implanted Silastic ECoG gird(s), in both computer simulations and in human experimentation. In an epilepsy patient undergoing surgical evaluation, the cortical potentials were reconstructed from the simultaneously recorded scalp EEG, in which main features of spatial patterns during interictal spike were preserved and over 0.75 correlation coefficient value was obtained between the recorded and estimated cortical potentials. The FEM-based CPI technique provides a means of connecting the simultaneous recorded ECoG and the scalp EEG, and promises to become an effective tool to evaluate and validate CPI techniques using clinic data.

Background Chronic lung disease and severe intraventricular hemorrhage or periventricular leukomalacia in premature infants are associated with abnormal neurodevelopmental outcomes. In a previous randomized, controlled, single-center trial of premature infants with the respiratory distress syndrome, inhaled nitric oxide decreased the risk of death or chronic lung disease as well as severe intraventricular hemorrhage and periventricular leukomalacia. We hypothesized that infants treated with inhaled nitric oxide would also have improved neurodevelopmental outcomes. Methods We conducted a prospective, longitudinal follow-up study of premature infants who had received inhaled nitric oxide or placebo to investigate neurodevelopmental outcomes at two years of corrected age. Neurologic examination, neurodevelopmental assessment, and anthropometric measurements were made by examiners who were unaware of the children's original treatment assignment. Results A total of 138 children (82 percent of survivors) were e...

Objective The present study aims to accurately estimate the in vivo brain-to-skull conductivity ratio by means of cortical imaging technique. Simultaneous extra- and intra-cranial potential recordings induced by subdural current stimulation were analyzed to get the estimation. Methods The effective brain-to-skull conductivity ratio was estimated in vivo for 5 epilepsy patients. The estimation was performed using multi-channel simultaneously recorded scalp and cortical electrical potentials during subdural electrical stimulation. The cortical imaging technique was used to compute the inverse cortical potential distribution from the scalp recorded potentials using a 3-shell head volume conductor model. The brain-to-skull conductivity ratio, which leads to the most consistent cortical potential estimates with respect to the direct intra-cranial measurements, is considered to be the effective brain-to-skull conductivity ratio. Results The present estimation provided consistent results in 5 human subjects studied. The in vivo effective brain-to-skull conductivity ratio ranged from 18 to 34 in the 5 epilepsy patients. Conclusions The effective brain-to-skull conductivity ratio can be estimated from simultaneous intra- and extra-cranial potential recordings and the averaged value/standard deviation is 25±7. Significance The present results provide important experimental data on the brain-to-skull conductivity ratio, which is of significance for accurate brain source localization using piece-wise homogeneous head models.

Background: It is of clinical importance to localize pathologic brain tissue in epilepsy. Noninvasive localization of cortical areas associated with interictal epileptiform spikes may provide important information to facilitate presurgical planning for intractable epilepsy patients. Methods: A cortical potential imaging (CPI) technique was used to deconvolve the smeared scalp potentials into the cortical potentials. A 3-spheres inhomogeneous head model was used to approximately represent the head volume conductor. Five pediatric epilepsy patients were studied. The estimated cortical potential distributions of interictal spikes were compared with the subsequent surgical resections of these same patients. Results: The areas of negativity in the reconstructed cortical potentials of interictal spikes in 5 patients were consistent with the areas of surgical resections for these patients. Conclusions: The CPI technique may become a useful alternative for noninvasive mapping of cortical regions displaying epileptiform activity from scalp electroencephalogram recordings. q 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

We have applied a cortical imaging technique (CIT) with a three-sphere head model to estimate cortical potentials from scalp electroencephalogram (EEG) recordings during interictal spikes in a pediatric epilepsy patient. The CIT analysis was performed during the ascending limb of interictal spikes and localized areas of activity were observed, overlying the epileptogenic zone, as being confirmed by the electrocorticography recordings and neurosurgical resections of the patient. The present study suggests that CIT may become a useful alternative for noninvasive localization of intracranial sources generating epileptiform activity from pre-operative scalp EEG recordings.

Neocortical slices including sensory cortex of mouse were used to study cellular and network activity during bicuculline evoked seizure-like activity. The relationship between the activities of single cells and the network was quantified using entropy measures of spike trains. The network shows a large increase in synchronous burst activity during the seizure-like phase. Surprisingly, the individual cells do not seem to follow this pattern of increased synchrony. It is hypothesized that the recruitment of silent units during the seizure onset may explain this paradoxical finding. Our data agrees with recent findings in experimental seizures and intra-operative recordings in humans.

Electric brain activity during seizures is often associated with hyperactive and synchronous bursts of activity. We investigated different protocols of electric stimulation in a model network as potential seizure control mechanisms. Our network consisted of a chain loop of cells with excitatory synapses, representing a neocortical microcircuit. Random fluctuations of the membrane potential in each neuron simulated activity originating from other areas. Overall depolarizing and hyperpolarizing currents were not effective in stopping synchronized activity in the network. An electric current proportional to the inverted field potential was an effective desynchronizing stimulus in smaller networks.

Non-linear measures (Kolmogorov entropy, correlation dimension and a surrogate based “z” score) of the underlying structure of the human neonatal EEG were made and compared to linear measures (eigenvalues) and to EEGs obtained from older children (greater than 3 years of age). Strong age-dependent differences were noted for Kolmogorov entropy, the surrogate-based measure of non-linearity and eigenvalues. The eigenvalues decrease with age and the Kolmogorov entropy increases with age. The measure of global non-linearity decreased with age so that it was positive in only a small fraction of the greater than 3-year-old subjects.

We assessed physicians working in the field of child neurology with the aim of improving the physicians' mental health. Our questionnaire included a burnout inventory and a general health questionnaire. We analyzed 29 responses from physicians in a variety of countries obtained through the Internet. According to their responses, 8 (27.5%) of the respondents had attained a burnout status, and 27 respondents (93.1%) had neurotic conditions. We found a greater percentage of physicians in poor mental health than we had found previously in assessments made in Japan. However, the respondents in the present survey had more positive styles for coping with stress. The length of time working as a physician affected respondents in Japan and internationally, whereas nationality or working environment (workplace, night shifts, and so on) did not. Consultants or mentors on work and assertive stress coping would be effective. Copyright 2003, Elsevier Science (USA). All rights reserved.

The development of a central hearing impairment is described in a young girl with risk factors for hearing impairment that included mosaic Down syndrome, leukemia, and chemotherapy. This case is unusual in the prospective regularity with which hearing was assessed from birth. The diagnosis is electrical status epilepticus in slow wave sleep, a rare childhood disorder, which was associated with lack of responsiveness to auditory signals, regression of emerging speech and language and other cognitive skills, and abnormal electroencephalographic (EEG) activity in both hemispheres. Treatment of the disorder with anticonvulsant medications and steroids has ameliorated the condition by suppressing the abnormal EEG activity and allowing substantial improvements in cognitive and social skills, although communication skills are improving more slowly. Abbreviations: ABR = auditory brainstem response, CPA = conditioned play audiometry, CSWS = continuous spikes and waves during slow wave sleep, EEG = electroencephalography, ESES = electrical status epilepticus of slow wave sleep, LKS = Landau-Kleffner syndrome, MRI = magnetic resonance imaging, MRL = minimal response level, REM = rapid eye movement, TEOAEs = transient evoked otoacoustic emissions, VRA = visual reinforcement audiometry

Neuropsychological and behavioral status were examined in 57 children aged 7 to 16 years with complex partial seizures (CPS) and compared with 27 sibling control children of the same age. Epilepsy had a significant effect on both cognitive and behavioral adjustment measures. Children with CPS had significant impairment across all seven cognitive domains assessed, reflective of a profile of relatively diffuse and generalized cognitive dysfunction. Age at onset of recurrent seizures was the strongest and most consistent predictor of adequacy of cognitive functioning; earlier age at onset was associated with poorer cognitive status. Children with CPS also had more problems compared with sibling control children on measures of social and school competence and internalizing behavior problems, but not externalizing behaviors. Further, frequency of seizure activity in the past year, rather than age at seizure onset, emerged as the strongest predictor of these behavioral difficulties. These findings are discussed in the context of understanding the impact of CPS on cognition and behavioral adjustment, and identifying the contribution of various aspects of the neurodevelopmental course of CPS to these issues.

Auditory event related potentials were recorded from neonatal, 3-month, and 3-year old rhesus monkeys. Auditory brainstem evoked responses (ABRs) were reliably recorded at all ages. ABR latencies decreased with age. Age effects were greater the more centrally generated the wave. Wave I amplitude decreased with age, Wave II increased, and Wave IV remained about the same. Stimulus rate effects were greater in neonates than older monkeys. Stimulus frequency also affected the ABR, but not differentially as a function of age. Recording montage had a significant effect on the recorded waveform. Wave I tended to be larger in amplitude in horizontal recordings and front–back recordings, while the later waves were relatively more prominent in more vertical montages. Middle latency evoked responses and late potentials were less reliably recorded than the ABR. Their reproducibility improved with age. Auditory event related potentials are promising measures of auditory function for research requiring nonhuman primate models of the developing human. © 1999 John Wiley & Sons, Inc. Dev Psychobiol 34: 37–56, 1999

We report 3 children without any brainstem auditory evoked potential (BAEP) neural component who all retained isolated cochlear microphonic potentials as well as click-evoked otoacoustic emissions. Two of them demonstrated only moderately impaired audiometric thresholds. These features correspond to a peculiar pattern of auditory dysfunction recently coined 'auditory neuropathy'. In contrast with the published previous cases of auditory neuropathy presenting with an acquired hearing deficit as children or young adults, all 3 children had a history of major neonatal illness and the auditory neuropathy was already demonstrated in the first months of their lives. (C) 1997 Elsevier Science Ireland Ltd.

When special pseudo-random stimuli sequences (maximum length sequences: MLS) are combined with a deconvolution analysis technique, it is possible to derive new evoked potential components that are called kernels. The kernels give a measure of the temporal interactions that take place between the responses to successive stimuli. This may provide an objective neurophysiological test for the exploration of a dimension of hearing which has hitherto been limited to psychophysical methods. Until now, auditory short-latency kernels obtained by the MLS method have been related to the late portion of the brainstem auditory evoked potential (BAEP), suggesting that temporal interactions occur rather late in the auditory pathways. We report 4 children without any BAEP neural components, who all retained isolated cochlear microphonic potentials. Three of them produced click-evoked otoacoustic emissions and two of them demonstrated only moderately impaired audiometric thresholds. This combination of absent BAEP neural components with preserved otoacoustic emissions and cochlear microphonic potential corresponds to a peculiar pattern of auditory dysfunction recently coined 'auditory neuropathy'. All 4 children exhibited well-defined kernels at latencies consistent with the microphonic potential. These data indicate that the cochlea itself can generate kernels at a presynaptic level. They open up the question of the identification of the physiological site(s) responsible for the generation of MLS-evoked kernels. (C) 1997 Elsevier Science Inland Ltd.

Auditory functioning was assessed in two groups of adult rhesus monkeys (11 years of age). One (n = 11) received modest exposure to lead early in life and the other (n = 8) served as controls and did not receive any lead supplementation. Two lead-exposed monkeys had abnormal distortion product otoacoustic emissions (DPEs) and smaller amplitude or absent evoked potentials. These monkeys had abnormal distortion product otoacoustic emission (DPEs) and smaller amplitude or absent evoked potentials. These monkeys had the highest blood levels recorded in their respective groups. For the remaining lead-exposed monkeys there was little difference between their DPEs and the DPEs of the control monkeys with one exception. DPE amplitudes of the control monkeys increased more rapidly as a function of stimulus level than those of the lead-exposed monkeys at most frequencies. There was also a significant but modest effect of lead exposure on the auditory brain stem evoked responses (ABRs) of these lead-exposed monkeys. There was no apparent effect on the middle latency evoked responses (MLRs), although that result could be due to the relatively greater variability of the MLR.

Early (ABRs) and middle (MLRs) surface-recorded auditory evoked potentials were compared in eight adult monkeys (Macaca mulatta) and eight adult humans. Responses whose probable generators were the cochlear nucleus and lateral lemniscus were of shorter latency and larger amplitude in monkeys. Relative to humans, ABR response latencies in monkeys were less affected by stimulus intensity, stimulus rate, and masker level. In contrast, monkey amplitudes were relatively more affected by those same stimulus parameters. The most prominent MLR wave was longer in latency and greater in amplitude in humans than the homologous wave in monkeys. The reduction in amplitude of that wave with increasing rate was greater for humans than monkeys. Temporal interactions (the effect of prior stimuli on the response to current stimulation) were investigated from a non-linear systems identification framework using maximum length sequences (MLSs). Both monkey and human auditory systems were second and probably third-order systems at the levels assessed. As the separations between the stimulus pulses decreased, evidence for temporal interactions became more prominent, reached a maximum, and then decreased with further decreases in stimulus pulse separation. At the highest stimulus rates presented, variations in temporal spacing among stimuli had less of an effect on monkey than human evoked responses.

A functional representation is proposed for complex valued (amplitude and phase) head-related transfer functions (HRTFs), including both frequency and spatial dependence. The frequency variation is spanned by a set of eigentransfer functions (EFs) that are generated using the Karhunen-Loève expansion. Any HRTF is represented as a weighted combination of the EFs where the weights are functions of the HRTFs spatial location and are termed spatial characteristic functions (SCFs). Samples of the SCFs are obtained by projecting the measured HRTFs onto the EFs. A regularization framework is employed to obtain a functional representation for the SCFs by fitting each set of SCF samples with a two-dimensional spline. Acoustic validation of the model's fidelity and predictive capability is provided using 2188 measured HRTFs from a KEMAR manikin and 1816 measured HRTFs from an anesthetized live cat. Errors between measured and modeled HRTFs are generally less than one percent. Larger errors occur in the contralateral regions for KEMAR and lower back regions for the cat as a consequence of the relatively small HRTF amplitudes resulting from head shadowing. Methods for reducing these errors are discussed.

In some cognitively delayed children who require a vagal nerve stimulator for treatment of their seizures, there is a risk of wound breakdown and infection from obsessive tampering with the wound. We describe the interscapular placement of the vagal nerve stimulator pulse generator as a method to reduce this risk.

In this article, a beamformer is proposed as a functional model for the spatial and temporal filtering characteristics of the external ear. The output of a beamformer is a weighted combination of the data received at an array of spatially distributed sensors. The beamformer weights and array geometry determine its spatial and temporal filtering characteristics. A procedure is described for choosing the weights to minimize the mean-squared error between the beamformer response and the measured response of the external ear. The effectiveness of the model is demonstrated by designing a beamformer of several hundred weights that duplicates and interpolates the measured external ear response of a cat over broad ranges of frequency and direction. A limited investigation of modeling performance as a function of array geometry is reported.

The purpose of this investigation was to describe the properties of averaged auditory evoked potential distortion products (AEP-DPs) in guinea pigs. This study provided a step toward developing a clinical index of nonlinear processing of auditory signals and supplied a baseline for studies evaluating the effect of cochlear damage on AEP-DPs. The amplitude of the AEP-DPs was evaluated as a function of f2/fl ratio (1.12–1.52) and primary frequency (500 Hz–2000 Hz). The amplitude of the AEP cubic difference tone (AEP-CDT) increased with increasing f2/fl ratio for the 500-Hz f1 primary and remained constant for the 800-Hz and 1700-Hz f1 primaries. The AEP-CDT generated by the 1100-Hz and 1400 Hz f1 primaries was maximum for the middle f2/fl ratios (1.22, 1.32, and 1.42). The AEP-CDT could not be distinguished from the noise floor for the 2000-Hz f1 primary. The AEP difference tone (AEP-DT) was larger and more frequently identified than the AEP-CDT. The amplitude of the AEP-DT decreased with an increase in f2/f1 ratio. The decrease was more pronounced for low-frequency f1 primaries than for high-frequency f1 primaries.

A consecutive, retrospective analysis of seizure control and quality of life was performed among 83 pediatric patients undergoing epilepsy surgery at Children's Hospital of Wisconsin. Seizure outcomes were generally favorable, with 68.7% class I outcomes; class II, 12%; and class III, 19.3%. Seizure freedom was highest among temporal lobectomies (84.2%) and hemispherectomies (76.2%). Outcomes among hemispherectomies were substantially superior to those of multilobar resections. Cortical dysplasia was associated with lower seizure freedom, at 57.5%. Among age groups, seizure-free outcomes in infants were lowest, at 50%. The lower infant seizure-free rate was likely attributable to frequency of multilobar resections and type of pathology (cortical dysplasia). Quality-of-life measures generally paralleled seizure outcomes. These results indicate that epilepsy surgery in children with intractable epilepsy can result in significant improvements in seizure control, quality of life, and development. Anticipated type of surgery, presumed location of epileptogenic site, absence of a defined lesion on magnetic resonance imaging scan of the brain, and patient's age should not prevent surgical evaluations of children with intractable epilepsy.

Brain-stem auditory-evoked responses (BAERs) were obtained in six normal-hearing adults using single-tone and two-tone stimuli arithmetically centered around 4000 Hz. Two-tone stimuli varied in frequency separation from 200 to 3200 Hz, and started in-phase (homophasic) or 180 deg out-of-phase (antiphasic) with each other. Responses to each of the single-tone components of the two-tone stimuli were elicited and then summed for comparison with responses to the two-tone stimuli. Results indicated no significant difference in wave V latency between homophasic or antiphasic two-tone conditions, and summed single-tone conditions. Under the homophasic condition, the mean latency for the widest frequency separation of the tones was significantly longer than those for narrower separations. A significant difference in wave V amplitude between two-tone phase conditions was found for frequency separations of 200, 400, and 3200 Hz only. Summed single-tone BAERs demonstrated a significantly larger wave V amplitude than responses from either two-tone phase condition at all frequency separations.

Spectral analysis of auditory-evoked potential recordings from ten normal-hearing subjects to two-tone signals revealed energy at difference tone (DT = f2-f1) and cubic difference (CDT = 2f1-f2) frequencies that was not present in the acoustic signal. Control experiments and calibrations provided substantial evidence supportive of the biological nature of these auditory nonlinearities, suggesting that they are not the result of electromagnetic, acoustic, or analytic artifact. Amplitudes of DT- and CDT-evoked responses were evaluated for rarefaction and condensation signals with f1 = 510 and 800 Hz across frequency ratios (f2/f1) of 1.16, 1.26, 1.36, and 1.46. Additionally, time-domain summation and subtraction of separately collected evoked responses to rarefaction and condensation signals were performed to demonstrate that these electrophysiological DT and CDT responses reflect their expected quadratic and cubic nature. Suggestions for development of clinical applications of assessing auditory nonlinearities using this methodology are provided.

Botulism in infants, unless recognized early, is associated with high mortality and morbidity. The diagnosis is suspected when infants present with sudden onset of weakness, respiratory failure, and constipation and is confirmed by demonstration of botulinum toxin in stool several weeks later. Electrodiagnosis allows quick and reliable confirmation of botulism. Low-amplitude compound muscle action potentials, tetanic or post-tetanic facilitation, and the absence of post-tetanic exhaustion support the diagnosis. Two infants with confirmed botulism did not exhibit the characteristic electrodiagnostic features, demonstrating the pitfalls in electrodiagnosis of infantile botulism. (J Child Neurol 1999;14:156-158).

Summary: Purpose: To develop and evaluate a new cortical activation mapping (CAM) method to obtain the neuronal activation sequences from the cortical potential distributions. Methods: Interictal electrocorticogram (ECoG) recordings were analyzed for eight pediatric epilepsy patients to find the cortical activation maps, which were compared with the patients' seizure-onset zones identified from ictal ECoG recordings. Various relations between the local activation time and cortical potential were assumed. The most effective relation was determined by accessing their capability to predict the seizure-onset zone. Computer simulations using a moving dipole source model were also conducted to test the present approach in imaging the propagated cortical activity. Results: In both clinical data analysis and computer simulations, the maximal amplitude proved to be the most effective criterion with which to determine the local cortical activation time. The present method successfully predicted the seizure-onset zone in seven of eight patients by the CAM analysis of ECoG-recorded interictal spikes (IISs). For patients with multiple seizure foci, each focus can be revealed by analyzing IISs with different spatial patterns. Conclusions: The time difference between spike peaks of the interictal events in the leading channel and other channels can be effectively defined as the local cortical activation time. The cortical activation mapping method based on this time latency can be used to predict the seizure-onset zones, suggesting that the present CAM method is useful to assist the presurgical evaluation for the epilepsy patients.

Invasive EEG monitoring is one of the best tools available for localization of epileptogenic foci in the brain. However, published data in mixed series of adult and pediatric patients show high incidence of epidural bacterial contamination, cerebrospinal fluid leakage, and skin infection after subdural electrode implantation. We sought to determine whether the complication rate from prolonged subdural electrode implantation would be lower in a purely pediatric series. Thirty-three subdural electrode implantation procedures were performed in 29 pediatric patients (age range 4–19) for an average of 7.2 days (range 3–14 days). Electrode number varied from 32 to >128 with a range of 4–11 electrode wires piercing the skin >1 cm from the primary incision. Of the 33 implantations and resections (66 craniotomies), 5 were for reimplantation. There were no permanent complications related to grid implantation. Transient complications included 1 case of prolonged prothrombin time and 1 patient with unexplained fever, both of which resolved upon removal of the grids. There were two culture-positive infections, one epidural and one superficial, both in patients undergoing reimplantation. There was no percutaneous cerebrospinal fluid leakage noted and no operation was aborted due to bleeding caused by grid placement. Our data suggest that subdural grid implantation in children is remarkably safe even for prolonged implantation, though infectious risk is significantly higher in reoperation (p = 0.019). This observation may contribute to lowering the threshold for two-stage invasive monitoring approaches in children with epilepsy.

Epilepsy is the second most common serious neurological disease after stroke. This disease affects approximately 50 million people worldwide and 50-70 cases per 100,000 in the developed countries. In approximately 40% of patients with so-called partial seizures, current medications are unable to control their symptoms. One of the most devastating aspects of epilepsy is the anxiety and apprehension associated with the inability to predict when a seizure will occur. The inability to predict the time of seizure onset also implies the need for continuous medication therapy with the associated continuous side effects. For a number of years investigators and commercial-interest groups have sought methods for the early detection and anticipation of seizures so that “discontinuous” therapies could be introduced (e.g., Milton and Jung, 2003). At the heart of most predictive efforts is the description and analysis of the cerebral electrical activity reflected in the electroencephalogram (EEG). The brain electrical activity of a patient with epilepsy shows abnormal and often rhythmic discharges during the seizure. This activity pattern is called an electrographic seizure. Between such electrographic seizures, short discharges (spikes) are also frequently observed in the EEG of these patients. Identification of these activity patterns in clinical practice has typically been a subjective process. The introduction of computer-based instrumentation and analysis to the field of electroencephalography made evaluation of automated spike and seizure detection techniques possible (e.g., Gotman and Gloor, 1976; Gotman et ai, 1979; Gotman, 1982). During the 1980s, the EEG during seizure activity was characterized using more complex measures such as those derived from chaos theory (e.g., Babloyantz and Destexhe, 1986; van Erp, 1988). There were a number of “early” reports of the successful application of frequency-domain template analyses and auto-regressive models to the problem of seizure prediction (e.g., Viglione and Walsh, 1975; Rogowski et al, 1981).

ObjectiveTo determine the accuracy of locating subdural electrodes by means of 3-D surface rendering of CT scans.\ud MethodsOpen source software has been developed and posted on the web which segments the electrodes into 3-D surfaces and allows their 3-D locations to be exported to other EEG analysis programs. The accuracy of the technique was determined by studying 410 subdural electrodes implanted in four epilepsy patients. Accuracy was determined by comparing the locations from the rendering analysis to the locations of the same electrodes determined by conventional analysis of their appearance on individual CT slices.ResultsThe average accuracy of a study of 410 electrodes imaged in four patients repeated two times by three observers was 0.91 (±0.41) mm, with a maximum error of 3.3 mm, about half of the diameter of an electrode.ConclusionsThe location of subdural electrodes can easily and quickly be determined within high-resolution CT scans through the use of 3-D rendering.SignificanceThis relatively fast and easy method for determining the location of subdural electrodes should facilitate their use in both clinical and research investigations.

The auditory system is represented by a third-order Volterra series, and the cross-section function resulting from applying the cross-correlation method with an m pulse sequence as the input is derived in terms of Volterra kernels. The function can be used to predict system responses to pulse trains of different pulse rates. It is therefore concluded that the m pulse sequence may be an effective and efficient stimulus for studying nonlinear rate effects in neurological systems. >

Measurements of electrical field potentials at the scalp are used to localize sources of electrical activity within the brain. Neuronal sources are modeled as current dipoles. The medum (brain, skull scalp) is linear so that the potential at the scalp is the superposition of the potentials from many active neurons. These properties are used to develop a mathematical model relating neural activity to the spatial distribution of the scalp potential. Linearly constrained minimum variance spatial filters are based on this model to estimate power as a function of position within the brain. Simulations illustrate the effectiveness of this approach for localizing an unknown number of sources. >

A functional representation for head-related transfer functions (HRTFs) is desirable as it overcomes many of the limitations associated with use of measured HRTFs. It provides a continuous representation of auditory space, such that the synthesis of HRTF at any given spatial location can be performed by functional evaluation of the model. Such a model that establishes a mathematical representation of the external ear transformation characteristics based on spatial feature extraction and regularization is proposed. >

Objective: This study describes the effect of train length, interstimulus interval, intertrain interval (ITI), and stimulus duration on the transition from the unadapted to the adapted wave V auditory evoked brain stem response (ABR). Design: ABRs were recorded to stimuli presented at two different rates: a slow rate characterizing the unadapted response and a fast rate characterizing the adapted response. Trains of stimuli (a sequence of stimuli separated by intervals of silence) also were presented. Different stimulus parameters defining the trains were varied. Results: Given a sufficiently long ITI, the latency prolongation to the first three or four stimuli in a train was rapid. It was similar for trains differing in number of stimuli. After the first three or four stimuli, there was a more gradual latency prolongation as a function of stimulus number. Shorter ITIs had the effect of prolonging the latencies to all the stimuli in the trains, reducing the rate of latency prolongation over the first few stimuli, and causing responses to trains of different length to differ (e.g., two click train responses were shorter latency than four click train responses). An unexpected result was the latency prolongation of wave Vs after the presentation of the stimulus trains. Conclusions: In response to a train of clicks, there seems to be a rapid increase in wave V latency to the first few clicks in the train followed by a more gradual latency prolongation to subsequent clicks in the train.

Distortion product otoacoustic emissions (DPOAEs) were compared in eight rhesus monkeys (Macaca mulatta) and eight normal hearing humans. DPOAEs were recorded in three conditions. In the first condition, DPOAEgrams were generated for monkeys and humans from approximately f2 = 0.5-20 kHz. Monkeys had larger amplitude DPOAEs at all frequencies except around f2 = 1 kHz. In the second condition, DPOAE amplitudes increased and then decreased as the separation between the primaries increased. These functions were similar in the two species except at the lowest frequencies assessed. In the third condition, the levels of the primaries were varied independently. Monkeys had steeper input/output (I/O) functions than humans. The slopes of DPOAE I/O functions increased with frequency in both species. When the levels of both primaries were increased simultaneously, DPOAE I/O functions were well described by power functions throughout the intensity range assessed (from threshold to 65 dB SPL). Monkey I/O functions tended to be expansive power functions at all but the lowest frequencies, while human I/O functions tended to be compressive power functions except at the highest frequencies assessed. Other differences in I/O functions f2 = 8 kHz may indicate species specific differences at high (for human) frequencies.

Objective: Two paradigms, the traditional binaural interaction (BI) paradigm and a maximum length sequence (MLS) BI paradigm were evaluated to investigate BI effects. Design: Evoked response BI effects were assessed at different levels of the auditory pathway in two experiments. Each experiment consisted of three conditions: a traditional BI paradigm using conventional stimuli, a traditional BI paradigm using MLS stimuli, and a MLS BI paradigm using MLS techniques to recover kernels reflecting BIs. Eleven normal-hearing young adults served as subjects. Results: There was evidence for BI effects on the auditory evoked brain stem response (ABR) and the middle latency response (MLR) using the traditional BI paradigm and conventional stimuli. With the same paradigm and MLS stimuli there was evidence for BI effects on the MLR but not the ABR. The more robust conventional effects may be explained by the larger amplitude evoked responses recorded conventionally due to the slower stimulation rates and more efficient signal to noise enhancement. BI effects were observed for both the ABR and MLR by recording BI kernels in the MLS BI paradigm. Conclusions: MLS BI kernels can be recorded in normal hearing adults. The MLS BI paradigm offers three potential advantages in recording binaural effects; avoidance of some of the methodological problems associated with traditional BI paradigms, faster stimulus rates permitting a more complete characterization of binaural rate effects, and more rapid data collection.

Two simultaneously presented maximum length sequences (MLSs) were used to investigate temporal nonlinearities. Not only did the recorded auditory evoked brain stem responses to these stimuli predictably increase in latency and decrease in amplitude as a function of the temporal interactions between MLSs, but thresholds were elevated by more than 20 dB. Simultaneous MLS paradigms make it possible to investigate a number of nonlinearities in the auditory system efficiently. This study also demonstrated that binaural MLS techniques can be used to assess auditory function even in individuals with asymmetric hearing losses without fear of crossover effects.