James D. Frost

Prospective study of outcome of infants with infantile spasms treated during controlled studies of ACTH and prednisone

We report the long-term outcome of 64 infants with infantile spasms, followed prospectively, using controlled treatment schedules and objective techniques (24-hour EEG and video monitoring) to determine response. Average age at follow-up was 50 months. Of the 64 infants, three (5%) died; of the others, 41 (67%) had developmental retardation of 50% or more or an IQ of 50 or less. Eight patients (13%) composed our cryptogenic study group and were so classified on the basis of normal CT scan, normal development prior to onset of infantile spasms, and undetermined cause. These patients had the better outcome; 38% had normal development or were only mildly retarded. Both the responders and nonresponders in our symptomatic group had a poor outcome; only 5% had normal development or mild impairment. Outcome was not significantly influenced by short versus long treatment lag or by response to therapy. Other types of seizures occurred in 34 patients (53%). In summary, the overall prognosis for long-term outcome in these 64 patients with infantile spasms was poor.

Tetanus toxin-induced seizures in infant rats and their effects on hippocampal excitability in adulthood

A new experimental model of developmental epilepsy is reported. Behavioral and EEG features of seizures produced by unilateral intrahippocampal injection of tetanus toxin in postnatal day 9-11 rats, are described. Within 24-72 h of tetanus toxin injection, rat pups developed frequent and often prolonged seizures which included combinations of repetitive wet dog shakes, and wild running-jumping seizures. Intrahippocampal and cortical surface EEG recordings showed that coincident with these behaviors, electrographic seizures occurred not only in the injected hippocampus, but also in the contralateral hippocampus and bilaterally in the neocortex. Analysis of the interictal EEG revealed multiple independent spike foci. One week following tetanus toxin injection, the number of seizures markedly decreased; however, interictal spiking persisted. After injection rats were allowed to mature some were observed to have unprovoked behavioral seizures and/or epileptiform EEG activity. Mature animals were also studied using in vitro slice techniques. Recordings from hippocampal slices demonstrated spontaneous epileptiform burst discharges in the majority of rats which had tetanus toxin induced seizures as infants. These events occurred in area CA3 and consisted of interictal spikes and intracellularly recorded paroxysmal depolarization shifts (PDSs). On rarer occasions, electrographic seizures were recorded. The use of the tetanus toxin model in developing rats may facilitate a better understanding of the unique features of epileptogenesis in the developing brain and the consequences early-life seizures have on brain maturation and the genesis of epileptic conditions in later life.

Detection of pseudosinusoidal epileptic seizure segments in the neonatal EEG by cascading a rule-based algorithm with a neural network

This paper presents an approach to detect epileptic seizure segments in the neonatal electroencephalogram (EEG) by characterizing the spectral features of the EEG waveform using a rule-based algorithm cascaded with a neural network. A rule-based algorithm screens out short segments of pseudosinusoidal EEG patterns as epileptic based on features in the power spectrum. The output of the rule-based algorithm is used to train and compare the performance of conventional feedforward neural networks and quantum neural networks. The results indicate that the trained neural networks, cascaded with the rule-based algorithm, improved the performance of the rule-based algorithm acting by itself. The evaluation of the proposed cascaded scheme for the detection of pseudosinusoidal seizure segments reveals its potential as a building block of the automated seizure detection system under development.

Quantifying motion in video recordings of neonatal seizures by robust motion trackers based on block motion models

This paper introduces a methodology for the development of robust motion trackers for video based on block motion models. According to this methodology, the motion of a site between two successive frames is estimated by minimizing an error function defined in terms of the intensities at these frames. The proposed methodology is used to develop robust motion trackers that rely on fractional block motion models. The motion trackers developed in this paper are utilized to extract motor activity signals from video recordings of neonatal seizures. The experimental results reveal that the proposed motion trackers are more accurate and reliable than existing motion tracking methods relying on pure translation and affine block motion models.

Chapter 63 – Infantile spasms

Infantile spasms are a unique disorder of infancy and early childhood. The average age at onset of infantile spasms is 6 months and the average incidence of the disorder is approximately 0.31 per 1000 live births. Approximately one-quarter of patients will spontaneously stop having spasms within 1 year of onset. There are three main types of epileptic spasms: flexor, extensor, and mixed flexor-extensor. Spasms frequently occur in clusters and commonly occur upon arousal from sleep. The motor spasms are frequently confused with other normal and abnormal infant behaviors. Typically, the interictal EEG reveals hypsarrhythmia or one of its variants. A variety of ictal EEG patterns may be seen, the most common of which is a generalized slow-wave transient followed by an attenuation of the background activity in all regions. The primary treatment objective is to improve the EEG and stop the spasms as soon as possible and to avoid prolonged treatment durations with any form of therapy. Currently, there is no conclusive evidence that medical or surgical treatment of infantile spasms significantly alters long-term outcome. Although the pathophysiological mechanism underlying infantile spasms is unknown, several animal models of infantile spasms have been developed in recent years.

An evaluation of quantum neural networks in the detection of epileptic seizures in the neonatal electroencephalogram

This paper presents the results of an experimental study that evaluated the ability of quantum neural networks (QNNs) to capture and quantify uncertainty in data and compared their performance with that of conventional feedforward neural networks (FFNNs). In this work, QNNs and FFNNs were trained to classify short segments of epileptic seizures in neonatal EEG. The experiments revealed significant differences between the internal representations created by trained QNNs and FFNNs from sample information provided by the training data. The results of this experimental study also confirmed that the responses of trained QNNs are more reliable indicators of uncertainty in the input data compared with the responses of trained FFNNs.

Improving the accuracy and reliability of motion tracking methods used for extracting temporal motor activity signals from video recordings of neonatal seizures

This paper presents an approach for improving the accuracy and reliability of motion tracking methods developed for video based on block motion models. This approach estimates the displacement of a block of pixels between two successive frames by minimizing an error function defined in terms of the pixel intensities at these frames. The minimization problem is made analytically tractable by approximating the error function using a second-order Taylor expansion. The improved reliability of the proposed method is illustrated by its application in the extraction of temporal motor activity signals from video recordings of neonatal seizures.

Automated tracking of multiple body parts in video recordings of neonatal seizures

This paper presents an automated procedure for tracking multiple body parts in video recordings of neonatal seizures. This procedure detects motion by relying on optical flow computation and then tracks one or more body parts by employing predictive block matching. Predictive block matching estimates the displacement of a feature between two successive frames by minimizing an error function defined in terms of the feature intensities at these frames. Displacement estimation is followed by adaptive block matching based on Kalman filtering. The reliability of the proposed automated tracking procedure is illustrated by its application in the extraction of temporal motor activity signals from video recordings of neonatal seizures.

Automatic interpretation of EEG: analysis of background activity.

Abstract A hierarchical approach to automation of EEG interpretation is described. The system utilizes an array of special-purpose processing units to accomplish parallel, real-time analysis of background activity in eight EEG channels. A PDP-11 40 computer is used to perform higher-order analytical functions and to generate both numerical and narrative reports. The systems design permits expansion of analysis capability by the incorporation of additional processing modules.

Vigabatrin therapy implicates neocortical high frequency oscillations in an animal model of infantile spasms.

Abnormal high frequency oscillations (HFOs) in EEG recordings are thought to be reflections of mechanisms responsible for focal seizure generation in the temporal lobe and neocortex. HFOs have also been recorded in patients and animal models of infantile spasms. If HFOs are important contributors to infantile spasms then anticonvulsant drugs that suppress these seizures should decrease the occurrence of HFOs. In experiments reported here, we used long-term video/EEG recordings with digital sampling rates capable of capturing HFOs. We tested the effectiveness of vigabatrin (VGB) in the TTX animal model of infantile spasms. VGB was found to be quite effective in suppressing spasms. In 3 of 5 animals, spasms ceased after a daily two week treatment. In the other 2 rats, spasm frequency dramatically decreased but gradually increased following treatment cessation. In all animals, hypsarrhythmia was abolished by the last treatment day. As VGB suppressed the frequency of spasms, there was a decrease in the intensity of the behavioral spasms and the duration of the ictal EEG event. Analysis showed that there was a burst of high frequency activity at ictal onset, followed by a later burst of HFOs. VGB was found to selectively suppress the late HFOs of ictal complexes. VGB also suppressed abnormal HFOs recorded during the interictal periods. Thus VGB was found to be effective in suppressing both the generation of spasms and hypsarrhythmia in the TTX model. Vigabatrin also appears to preferentially suppress the generation of abnormal HFOs, thus implicating neocortical HFOs in the infantile spasms disease state.