SUMMARYThe diagnosis, evaluation, and management of infantile spasms (IS) continue to pose significant challenges to the treating physician. Although an evidence-based practice guideline with full literature review was published in 2004, diversity in IS evaluation and treatment remains and highlights the need for further consensus to optimize outcomes in IS. For this purpose, a working group committed to the diagnosis, treatment, and establishment of a continuum of care for patients with IS and their families-the Infantile Spasms Working Group (ISWG)-was convened. The ISWG participated in a workshop for which the key objectives were to review the state of our understanding of IS, assess the scientific evidence regarding efficacy of currently available therapeutic options, and arrive at a consensus on protocols for diagnostic workup and management of IS that can serve as a guide to help specialists and general pediatricians optimally manage infants with IS. The overall goal of the workshop was to improve IS outcomes by assisting treating physicians with early recognition and diagnosis of IS, initiation of short duration therapy with a first-line treatment, timely electroencephalography (EEG) evaluation of treatment to evaluate effectiveness, and, if indicated, prompt treatment modification. Differences of opinion among ISWG members occurred in areas where data were lacking; however, this article represents a consensus of the U.S. approach to the diagnostic evaluation and treatment of IS.

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Infantile spasms is a unique disorder peculiar to infancy and early childhood. In this article, the clinical manifestations and electroencephalographic features of the disorder are described. The possible pathophysiologic mechanisms underlying infantile spasms and the relation of this disorder to other childhood encephalopathies are discussed. Finally, the treatment of patients with infantile spasms and their long-term outcome are briefly reviewed.

With the use of a time-synchronized video and polygraphic recording system, 5,042 infantile spasms were monitored and analyzed in 24 infants aged 1 to 43 months. Of these, 33.9% were flexor, 22.5% extensor, and 42.0% mixed flexor-extensor. Sometimes the spasms were followed by a period of akinesia and diminished responsiveness lasting up to 90 seconds, and rarely (1.0%) this "arrest" effect constituted the entire seizures. More than one type of seizure occurred in 21 of the 24 infants. In the same number, 78.3% of the seizures occurred in clusters, and the intensity and frequency of the spasms in each cluster often increased to a peak, then progressively decreased until they stopped. Predominantly, the clusters occurred soon after arousal from sleep. The number of seizures occurring at night (55.2%) was similar to the diurnal number (44.8%). The electroencephalographic seizure pattern was variable, but a marked generalized attenuation of electrical activity was a feature of 71.7% of the attacks. Attenuation episodes of similar degree and duration occurred with no evidence of a seizure.

Infantile spasms syndrome (ISS) is

Prolonged monitoring studies of patients with infantile spasms have shown that hypsarrhythmia is a highly variable and dynamic electroencephalographic pattern. Variations of the prototypic pattern (modified hypsarrhythmia) include hypsarrhythmia with increased interhemispheric synchronization, asymmetrical hypsarrhythmia, hypsarrhythmia with a consistent focus of abnormal discharge, hypsarrhythmia with episodes of attenuation, and hypsarrhythmia comprising primarily high-voltage slow activity with little sharp-wave or spike activity. Marked changes in the hypsarrhythmic pattern usually occur during sleep, chiefly during rapid eye movement sleep, when there is a marked reduction in, or total disappearance of, the hypsarrhythmic pattern. Relative normalization of the hypsarrhythmic pattern can also be seen immediately on arousal and during clusters of infantile spasms. Thus, the specific EEG features seen in a given patient depend on multiple factors, including the duration of the EEG recording, the clinical state of the patient, and the presence of various structural abnormalities of the brain.

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SUMMARYPurpose: Infantile spasms is one of the most severe epileptic syndromes of infancy and early childhood. Progress toward understanding the pathophysiology of this disorder and the development of effective therapies has been hindered by the lack of a relevant animal model. We report here the creation of such a model. Methods: The sodium channel blocker, tetrodotoxin (TTX), was chronically infused into the developing neocortex or hippocampus of infant rats by way of an osmotic minipump starting on postnatal day 10-12. Results: After a minimum of 10 days of infusion, approximately one-third of these rats began to display very brief (1-2 s) spasms, which consisted of symmetric or asymmetric flexion or extension of the trunk and sometimes involvement of one or both forelimbs. The typical ictal EEG pattern associated with the behavioral spasms consisted of an initial generalized, high amplitude, slow wave followed by an electrodecrement with superimposed fast activity. The interictal EEG revealed multifocal spikes and sharp waves, and in most animals that had spasms a hypsarrhythmic pattern was seen, at least intermittently, during NREM sleep. Like in humans, the spasms in the rat often occurred in clusters especially during sleep-wake transitions. Comparison of the ictal and interictal EEGs recorded in this model and those from humans with infantile spasms revealed that the patterns and the frequency components of both the ictal events and hypsarrhythmia were very similar. Discussion: The TTX model of infantile spasms should be of value in furthering an understanding of the pathophysiology of this seizure disorder.