The onset of pediatric refractory status epilepticus is not distributed uniformly during the day.

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).

Haemodynamic response associated with both ictal and interictal epileptiform activity using simultaneous video electroencephalography/near infrared spectroscopy in a within-subject study.

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.

Noninvasive cortical imaging of epileptiform activities from interictal spikes in pediatric patients.

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.

Efficacy of felbamate in the treatment of intractable pediatric epilepsy.

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.

Epilepsy surgery outcomes: quality of life and seizure control.

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.

Frequency domain analysis of human subdural recordings.

SUMMARY: It is possible to localize many aspects of cortical function and dysfunction without the use of direct electrical stimulation of cortex. This study explores the degree to which information can be obtained about functional cortical organization relative to epileptogenic regions through analysis of electrocorticographic recordings in the frequency domain. Information about the extent of seizure regions and the location of the normal sensory and motor homunculus and some higher language and memory related areas can be obtained through the analysis of task-related power spectrum changes and changes in lateral interelectrode coherence patterns calculated from interictal and ictal recordings.

Cortical activation mapping of epileptiform activity derived from interictal ECoG spikes.

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.

Low incidence of subdural grid-related complications in prolonged pediatric EEG monitoring.

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.

A cortical potential imaging study from simultaneous extra- and intracranial electrical recordings by means of the finite element method.

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 postoperative 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 conductive 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.

Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide.

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 evaluated. In the group given inhaled nitric oxide, 17 of 70 children (24 percent) had abnormal neurodevelopmental outcomes, defined as either disability (cerebral palsy, bilateral blindness, or bilateral hearing loss) or delay (no disability, but one score of less than 70 on the Bayley Scales of Infant Development II), as compared with 31 of 68 children (46 percent) in the placebo group (relative risk, 0.53; 95 percent confidence interval, 0.33 to 0.87; P=0.01). This effect persisted after adjustment for birth weight and sex, as well as for the presence or absence of chronic lung disease and severe intraventricular hemorrhage or periventricular leukomalacia. The improvement in neurodevelopmental outcome in the group given inhaled nitric oxide was primarily due to a 47 percent decrease in the risk of cognitive impairment (defined by a score of less than 70 on the Bayley Mental Developmental Index) (P=0.03). CONCLUSIONS: Premature infants treated with inhaled nitric oxide have improved neurodevelopmental outcomes at two years of age.

Locating chronically implanted subdural electrodes using surface reconstruction.

OBJECTIVE: To determine the accuracy of locating subdural electrodes by means of 3-D surface rendering of CT scans. METHODS: Open 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. RESULTS: The 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. CONCLUSIONS: The location of subdural electrodes can easily and quickly be determined within high-resolution CT scans through the use of 3-D rendering. SIGNIFICANCE: This relatively fast and easy method for determining the location of subdural electrodes should facilitate their use in both clinical and research investigations.

Seizure anticipation in pediatric epilepsy: use of Kolmogorov entropy.

The purpose of this paper is to demonstrate feasibility of using trends in Kolmogorov entropy to anticipate seizures in pediatric patients with intractable epilepsy. Surface and intracranial recordings of preseizure and seizure activity were obtained from five patients and subjected to time series analysis using Kolmogorov entropy. This metric was compared with correlation dimension and power indices, both known to predict seizures in some adult patients. We used alarm levels and introduced regression analysis as a quantitative approach to the analysis of trends. Surrogate time series evaluated data nonlinearity, as a precondition to the use of nonlinear measures. Seizures were anticipated before clinical or electrographic seizure onset for three of the five patients from the intracranial recordings, and in two of five patients from the scalp recordings. Anticipation times varied between 2 and 40 minutes. This is the first report in which simultaneous surface and intracranial recording are used for seizure prediction in children. We conclude that the Kolmogorov entropy and power indices were as effective as the more commonly used correlation dimension in anticipating seizures. Further, regression analysis of the Kolmogorov entropy time series is feasible, making the analysis of data trends more objective.

An assessment of the mental health of physicians specializing in the field of child neurology.

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.

Interscapular placement of a vagal nerve stimulator pulse generator for prevention of wound tampering. Technical note.

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.