An avian model of genetic reflex epilepsy.

The Fayoumi strain of chickens (Fepi) carries a recessive autosomal gene mutation in which homozygotes are afflicted with a photogenic and audiogenic reflex epilepsy. Seizures consist of stimulus-locked motor symptoms followed by generalized self sustained convulsions. EEG recordings show spikes and spike and waves patterns at rest which are suppressed during seizures and replaced by a desynchronized pattern of activity. Neurones of the prosencephalon discharge in bursts at rest, while neurones of the mesencephalon are bursting during seizures. Living neural chimeras were obtained by replacing specific embryonic brain vesicles in a normal chicken embryo with equivalent vesicles from a Fepi donor. These chimeras show that the epileptic phenotype can be totally or partially transferred from the Fepi to the normal chickens. Total transfer of photogenic and audiogenic seizures was obtained by substitution of both the prosencephalon and mesencephalon, while substitution of the prosencephalon alone resulted in transfer of interictal paroxysmal activity and substitution of the mesencephalon alone resulted principally in transfer of ictal motor symptoms. Increased expression of the c-fos protooncogene, as revealed by the western blot technique, confirmed the distinct encephalic localizations of the symptoms of the photogenic and audiogenic reflex epilepsy of the Fepi shown with the methods of electrophysiology and brain chimeras. We conclude that the Fepi is a good model of brain stem reflex epilepsy and suggest that the brain stem is a generator of some other animal and human genetic reflex "epileptic syndromes".

Medical technology assessment photic stimulation--standardization of screening methods.

RATIONALE: In many EEG laboratories in Europe, intermittent photic stimulation (IPS) is not performed routinely, and consequently, great variation exists in the type of photo stimulator used, the methodology employed, and the interpretation of the EEG curves, thus leading to different outcomes. METHODOLOGY: It was decided to hold a consensus meeting with experts in the field of photic stimulation from various European countries. This meeting was held at the Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands. The consensus reached was presented and discussed at the 9th European Congress of Clinical Neurophysiology in Ljubjana in June 1998. RESULTS: Patients should be positioned at a distance of 30 cm from the photic stimulator (nasion to lamp) with dim surrounding lights, just enough to see the patient. Flashes should be delivered in separate trains of 10 s for each frequency, with intervals of 7 s minimum. First stimulation occurs with eyes open followed after 5 s by eye closure, while starting at 1 Hz progressing to 20 Hz, unless generalised epileptiform discharges are evoked at a lower frequency. Then, frequencies should start at 60 Hz decreasing to 25 Hz. The following frequencies should be used: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 60, 50, 40, 30 and 25 Hz. The total duration is a maximum of 6 min (patients without a reaction to IPS). In interpreting the evoked responses, a clear distinction should be made between epileptiform responses confined to the occipital area (OSW), starting occipitally and spreading to frontal regions (OGSW), or generalised from the start (GSW). Other responses include generalised spikes (OR). CONCLUSION: This standard is safe, relatively quick, simple and reliable. Comparison of data within patients and between patients of various laboratories will also be possible. This will improve the quality of the care of the individual patient and make collaborative research possible.

Epilepsies and video games: results of a multicentric study.

OBJECTIVES: The purpose of this study was to research whether or not video games may induce paroxysmal discharges (PD) in different groups of patients. METHODS: One hundred and fifteen subjects from 5 different French laboratories were studied: 33 had seizures exclusively under visual stimuli, 42 had both photogenic seizures and spontaneous seizures occuring independently, and 40 had non-photogenic seizures. The same protocol which included one TV sequence, 3 sequences of video games selected on particular criteria (pattern, luminosity and nature of the scene), were presented at different distances from the TV screen at 50 and 100 Hz. RESULTS: Among the factors provoking paroxysmal discharges (PD) some seem crucial: the frequency of the TV screen (the 100 Hz screen was significantly safer than 50 Hz), the distance from the screen (1 m safer than 50 cm), and, particularly for the 50 Hz screen, the specific pattern of the images and the act of playing. CONCLUSIONS: Video games are ineffective for subjects known as having a non-photosensitive epilepsy, but may induce PD on subjects known as photosensitive even when intermittent light stimulation (ILS) is not effective. These results based on a different approach than in other publications confirm data which were suggested by the literature, and suggest that 100 Hz TV screens should be recommended to patients with TV-induced attacks.

General recommendations.

NASA: Recommendations from a workshop on Space Neuroscience Research held in Paris on April 22-24, 1997 are summarized. Research areas include the autonomic nervous system, development and neurobiology, posture and movement, visual perception, vestibular function, cognition, and human factors. Long-term neuroscience research studies are being planned for the International Space Station. Experiments in microgravity should be accompanied by appropriate, ground-based research on the effects of gravity.^ieng

EEG and sleep disturbances during dives at 450 msw in helium-nitrogen-oxygen mixture.

To study the effects of nitrogen addition to the breathing mixture on sleep disturbances at pressure, two dives were performed in which helium-nitrogen-oxygen mixture was used up to 450 m sea water (msw). In total, sleep of 12 professional divers was analyzed (i.e., 184 night records). Sleep was disrupted by compression and by stay at 450 msw: we observed an increase in awake periods and in sleep stages I and II and a decrease in stages III and IV and in rapid-eye-movement sleep periods. These changes, which were more intense at the beginning of the stay, began to decrease from the seventh day of the stay, but the return to control values was recorded only during the decompression at depths below 200 msw. These changes were equivalent to those recorded in other experiments with helium-oxygen mixture in the same range of depths and were independent of the intensity of changes recorded in electroencephalographic activities in awake subjects.

Brain chimeras in birds: application to the study of a genetic form of reflex epilepsy.

A strain of chicken, called here FEpi (for Fayoumi epileptic), bearing an autosomal recessive mutation, exhibits a form of reflex epilepsy with EEG interictal paroxysmal manifestations and generalized seizures in response to either light or sound stimulations. By using the brain chimera technology, we demonstrate here that the epileptic phenotype can be partially or totally transferred from an FEpi to a normal chick by grafting specific regions of the embryonic brain. The mesencephalon contains the generator of all epileptic manifestations whether they involve visual or auditory neuronal circuits, with the exception of the abnormal EEG which is transmitted exclusively by telencephalic grafts. This analysis supports the hypothesis that certain forms of human and mammalian epilepsies have a brainstem origin.

Electrographic studies of the effects of RP 60180, a novel kappa agonist, on the photosensitive baboon Papio papio.

1. The authors describe here the effects of intravenous administration of RP 60180, a novel kappa agonist, on conscious baboons of the species Papio papio, which spontaneously present photically induced epileptic responses. 2. Animals (n = 2) were chronically implanted with epidural recording electrodes and tested whilst seated in a primate chair. The electrocorticogram (ECoG) and electrocardiogram (ECG) were recorded during a control period of at least 30 minutes before the injection of RP 60180 (1 to 4.5 mg/kg i.v.) and immediately afterwards. 3. Qualitatively, up to the dose of 4.5 mg/kg i.v., RP 60180 did not modify ECoG background in term of paroxysmal activity in comparison with that observed during the control period. It did not cause any manifest focal or generalized seizure discharges, nor did it consistently enhance or reduce photically induced myoclonic responses. 4. From the dose of 1 mg/kg i.v., RP 60180 slowed ECG frequency. This effect, which lasted for about 30 minutes post-injection, was most often seen at the higher doses. 5. In another set of experiments, one baboon received the kappa agonist U-50488 (a benzacetamide derivative of spiradoline) at 1 and 3 mg/kg i.v. U-50488, at 3 and to a lesser degree at 1 mg/kg i.v., induced paroxysmal bursts of slow wave ECoG activity and a slowing of the ECG. These effects lasted about 1 hour post-drug administration. During this period, we observed spontaneous vocalization, as if the animal were complaining, as well as shaking.

Brain chimeras for the study of an avian model of genetic epilepsy: structures involved in sound and light-induced seizures.

The epileptic homozygotes of the Fayoumi strain of chickens (Fepi) are affected by photogenic reflex epilepsy with complete penetrance. Here we demonstrate that they are equally affected by audiogenic reflex epilepsy induced by intense sound stimulation. All the Fepi display sound-induced seizures from hatching to adulthood consisting of initial 'ictal arousal' and running fits usually followed by generalized clonico-tonic convulsions. A running fit is the preconvulsive motor symptom specifically induced by auditory stimulation while neck myoclonus is the preconvulsive motor symptom specifically induced by photic stimulation. The EEG interictal spikes and spike and waves are suppressed and replaced by a desynchronized trace during the seizures of both kinds. Viable neural chimeras were obtained by graft of embryonic brain vesicles from Fepi donors into normal chick embryos. Transfer of the complete audiogenic and photogenic phenotypes was obtained in chimeras resulting from embryonic substitution of both the prosencephalon and mesencephalon. The substitution of the prosencephalon alone resulted in transfer of interictal paroxysmal EEG activity accompanied by the sound and light-induced desynchronization and 'ictal arousal' with no motor seizures. Chimeras with embryonic substitution of the mesencephalon alone displayed running fits and convulsions induced by sound stimulation but only neck myoclonus following light stimulation. The conclusions are reached that: (i) the Fepi is a model of audiogenic and photogenic reflex epilepsy; (ii) in both types, the seizure initiator and the convulsion generator are localized in the brainstem, although reinforcement from telencephalic visual structures is needed to trigger photogenic generalized convulsions.

Reflex epilepsy in the Papio-papio baboon, particularly photosensitive epilepsy.

Papio-papio baboons may present two types of reflex paroxysmal manifestations: --Myoclonia and generalized seizures are induced by intermittent light stimulation in predisposed animals; this photosensitive epilepsy resembles that observed in some human patients; it involves mainly the cerebral cortex during myoclonia which are accompanied by EEG paroxysmal discharges, and the mesencephalic reticular formation during seizures; --Myoclonia of a different type, never accompanied by EEG paroxysmal discharged and never evolving into seizures, may occur during movement or agitation of predisposed animals; these myoclonia are considered "non-epileptic" since they do not involve the cerebral cortex but probably the lower brain stem; they resemble that observed in startle disease or in some human degenerative disorders. The paper demonstrates that these manifestations constitute two different entities with clinical and electrophysiological characteristics as well as pharmacological reactivities completely different one from the other. Their "epileptic" or "non-epileptic" nature is discussed.

Reflex epilepsy of the fowl and its transfer to normal chickens by brain embryonic grafts.

The genetic photosensitive epilepsy of the Fayoumi chicken was transferred to normal chickens by in situ grafts at 2 days of incubation, of both the prosencephalic and mesencephalic brain vesicles taken from epileptic embryos. However, mesencephalic graft is sufficient to allow convulsions under sound stimulation. Typical EEG patterns are recorded in chimeras having the prosencephalon plus or not the mesencephalon. We conclude that, in this mutant, the whole neural tissue is affected, but the seizure generator is localized inside the mesencephalon, and specific sensory pathways are necessary for seizures to occur.

Development of epileptic activity in embryos and newly hatched chicks of the Fayoumi mutant chicken.

The homozygous Fayoumi strain of epileptic chickens (Fepi) is affected by generalized convulsions consistently induced by intermittent light stimulation (ILS) and by intense sound. Although interictal EEG recordings show continuous spikes and spike and wave activity, desynchronization and flattening (DF) of the EEG are observed during seizures. We have studied development of the epileptic phenotype in embryonic (E) and posthatching (P) Fepi. As compared with those of chicken embryos of a normal strain, no differences were observed in the EEG before embryonic day (E) 16. Clearly differentiated spikes and spike and waves appeared at E17 in Fepi. Metrazol-induced EEG seizures were observed at E16 in normal embryos and at E17 in Fepi. The Fepi showed some characteristics: Spontaneous EEG seizure-like discharges also appeared at E17 but decreased toward hatching; visual or acoustic hyperexcitability developed at E20 together with evoked responses in normal chickens; desynchronization of the EEG, typical of the epileptic seizure of the adult, could be induced by ILS at B20, but ILS- or sound-induced generalized motor seizures appeared at P1, a few hours after hatching. Results show that Fepi phenotype reaches full expression at P1, but the electric paroxysms are expressed earlier, paralleling synaptic maturation.

High expression of noradrenaline, choline acetyltransferase and glial fibrillary acidic protein in the epileptic focus consecutive to GABA withdrawal. An immunocytochemical study.

Interruption of a chronic GABA infusion into the rat somatosensory cortex induces the appearance of focal epileptic manifestations, known as the 'GABA withdrawal syndrome' (GWS). The aim of the present study was to determine, by immunocytochemistry, if neurotransmitters other than GABA are involved in GWS, namely: noradrenaline (NA), serotonin, choline acetyltransferase (CAT), cholecystokinin, neuropeptide Y, somatostatin and glial fibrillary acid protein (GFAP). Immunocytochemical data were compared in three animal groups: GABA-, saline- and L-aspartate (L-Asp)-infused rats. Only GABA-infused rats presented epileptic manifestations after interruption of the infusion. Saline- and L-Asp-infused rats served as controls. Observations were limited to the region surrounding the cortical infusion site. GABA-infused rats showed in the zone of the epileptic focus a number of cell bodies strongly immunoreactive to NA antibodies much larger than control rats. In addition, NA-immunoreactive fibers formed a dense plexus and some of them were observed around perikarya. In saline- and L-Asp-infused rats, the NA-immunolabelled fibers were sparse and NA immunolabelling was rarely observed in cell bodies. These results contrast to those obtained for the serotonergic system, where no significant difference was observed among the three groups of rats. CAT immunolabelling was observed in cell bodies, but not in nerve terminals in rats of the three groups. The number of CAT-immunoreactive cell bodies was much greater in GABA-infused rats than in the control animals. GFAP immunolabelling showed an important number of astrocytes throughout the cortex of the GABA-infused hemisphere, whereas, astrocytic reaction was limited to the infusion site in controls. Immunocytochemical data concerning peptides revealed cortical neuronal elements labelled similarly in the three groups of rats. Noradrenergic, cholinergic and glial modifications observed mainly in GABA-infused rats can result from lesion and from a specific action of GABA in chronic infusion. These modifications may contribute to the epileptogenesis of GWS, as recently demonstrated by electrophysiological recordings that show a modulating action of NA on firing activity of neurons involved in the epileptic focus.