Richard A Hrachovy

PURPOSE: 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 ...

Twenty-four patients with infantile spasms were entered in a double-blind, placebo-controlled, crossover study to compare the therapeutic effectiveness of ACTH (20 to 30 units/day) with that of prednisone (2 mg/kg/day). Response to therapy was determined by utilizing a comprehensive monitoring system and was defined as a complete cessation of spasms and disappearance of the hypsarrhythmic EEG pattern. A major difference between the effectiveness of ACTH and that of prednisone in stopping ...

Studies were conducted to characterize a chronic epileptic condition that follows recurrent seizures induced by intrahippocampal tetanus toxin injection in infancy. Wistar rat pups received a single injection of tetanus toxin in the right CA3 region on postnatal day 10. Animals were monitored for epileptiform activity by video electroencephalographic or visual observation during the following three to five days. Repeat evaluation six months later demonstrated interictal discharges in 79% ...

BACKGROUND: Postoperative electroencephalographic (EEG) seizures are reported to occur in 14% to 20% of neonates after cardiac surgery with cardiopulmonary bypass (CPB). EEG seizures are associated with prolonged deep hypothermic circulatory arrest and with adverse long-term neurodevelopmental outcomes. We performed video/EEG monitoring before and for 72 hours after neonatal cardiac surgery, using a high-flow CPB protocol and cerebral oxygenation monitoring, to ascertain incidence, ...

PURPOSE: Depression is a highly prevalent, relatively underdiagnosed and undertreated comorbid condition in epilepsy. The purpose of this study was to determine the effect of using a validated self-reporting depression scale on the ability to detect depression in people with epilepsy receiving care in a busy clinical setting.

METHODS: The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a 6-item questionnaire validated to screen for depression in people with epilepsy. ...

Infantile spasms syndrome (ISS) is a catastrophic pediatric epilepsy with motor spasms, persistent seizures, mental retardation, and in some cases, autism. One of its monogenic causes is an insertion mutation [c.304ins (GCG)(7)] on the X chromosome, expanding the first polyalanine tract of the interneuron-specific transcription factor Aristaless-related homeobox (ARX) from 16 to 23 alanine codons. Null mutation of the Arx gene impairs GABA and cholinergic interneuronal migration but ...

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 ...

Infantile spasms constitute a relatively rare disorder of infancy and early childhood; their onset is usually within the first 6 to 8 months of life. A large percentage of patients with this disorder (85-90 per cent) show various degrees of retardation. Infantile spasms typically occur in clusters immediately on arousal, or soon thereafter, but rarely occur while the infant is actually asleep. The usual interictal EEG pattern associated with infantile spasms is hypsarrhythmia, but ...

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 ...

PURPOSE: Kv4.2 subunits contribute to the pore-forming region of channels that express a transient, A-type K(+) current (A-current) in hippocampal CA1 pyramidal cell dendrites. Here, the A-current plays an important role in signal processing and synaptic integration. Kv4.2 knockout mice show a near elimination of the A-current in area CA1 dendrites, producing increased excitability in this region. In these studies, we evaluated young adult Kv4.2 knockout mice for spontaneous seizures and ...

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 ...

OBJECTIVE: This study was aimed at the development of a seizure detection system by training neural networks using quantitative motion information extracted by motion segmentation methods from short video recordings of infants monitored for seizures.

METHODS: The motion of the infants' body parts was quantified by temporal motion strength signals extracted from video recordings by motion segmentation methods based on optical flow computation. The area of each frame occupied by the ...

Extracelluar signal-regulated kinase (ERK) pathway activation has been demonstrated following convulsant stimulation; however, little is known about the molecular targets of ERK in seizure models. Recently, it has been shown that ERK phosphorylates Kv4.2 channels leading to down-regulation of channel function, and substantially alters dendritic excitability. In the kainate model of status epilepticus (SE), we investigated whether ERK phosphorylates Kv4.2 and whether the changes in Kv4.2 ...

During brain development, neuronal activity can transform neurons characterized by widely ranging axonal projections to ones with more restricted patterns of synaptic connectivity. Previous studies have shown that an exuberant outgrowth of local recurrent excitatory axons occurs in hippocampal area CA3 during postnatal weeks 2 and 3. Axons are remodeled with maturation, and nearly half of the branches are eliminated. Postnatal weeks 2 and 3 also coincide with a "critical" period of ...

Studies were undertaken to examine the effects recurrent early-life seizures have on the ability of rats to acquire spatial memories in adulthood. A minute quantity of tetanus toxin was injected unilaterally into the hippocampus on postnatal day 10. Within 48 h, rats developed recurrent seizures that persisted for 1 week. Between postnatal days 57 and 61, rats were trained in a Morris water maze. Toxin-injected rats were markedly deficient in learning this task. While these rats showed ...